Compare Ceftazidime-Avibactam + Metronidazole vs Meropenem for hospitalized adults with complicated Intra-Abd Infections - RECLAIM3

Study identifier:D4280C00018

ClinicalTrials.gov identifier:NCT01726023

EudraCT identifier:2011-003893-97

CTIS identifier:N/A

Study Complete

Official Title

A Phase III, Randomized, Multicenter, Double Blind, Double-Dummy, Parallel-Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-Abdominal Infections In Hospitalized Adults

Medical condition

Complicated Intra-Abdominal Infection

Phase

Phase 3

Healthy volunteers

Study drug

Ceftazidime-avibactam, metronidazole, Meropenem

Sex

All

Actual Enrollment

486

Study type

Interventional

Age

18 Years - 90 Years

Date

Study Start Date: 14 Jan 2013

Primary Completion Date: 14 Mar 2015

Study Completion Date: 14 Mar 2015

Study design

Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 May 2017 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Beijing, China

Location

Research Site

Chongqing, China

Location

Research Site

Shanghai, China

Location

Research Site

Guangzhou, China

Location

Research Site

changsha, China

Location

Research Site

Jiangyin, China

Location

Research Site

Wuxi, China

Location

Research Site

Nan Chang, China

Arms	Assigned Interventions
Experimental: Ceftazidime-Avibactam plus metronidazole	Drug: Ceftazidime-avibactam Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Drug: metronidazole Metronidazole 500mg/100ml solution for infusion
Active Comparator: Meropenem	Drug: Meropenem Meropenem powder for solution for infusion 1000mg

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Overall, 486 patients were enrolled from 43 centers in 3 countries in this study. The first patient was enrolled on 14 January 2013 and the last patient last visit was on 14 March 2015.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 486 enrolled patients, 42 did not meet the eligibility criteria. A further two patients were not randomized due to withdrawn consent, and one patient was not randomized due to unavailability of study drug.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Participant Flow: Overall Study

	Ceftazidime-Avibactam plus metronidazole	Meropenem
STARTED	219	222
COMPLETED	190	196
NOT COMPLETED	29	26
Death	1	1
Lost to Follow-up	5	10
Other Eligibility criteria	7	7
Withdrawal by Subject	16	8

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Baseline analysis population is MITT ; Randomized patients who received any amount of study therapy, excluding patients who received both study therapies. 9 patients were randomized but not treated, and one patient received doses of both treatments.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Baseline Measures

	Ceftazidime-Avibactam plus metronidazole	Meropenem	Total
Number of Participants [units: Participants]	214	217	431
Age Continuous [units: Years] Mean ± Standard Deviation	48.5 ± 16.83	48.5 ± 17.43	48.5 ± 17.11
Age, Customized [units: Participants]
18-45 Years	89	96	185
46-64 Years	85	72	157
65-74 Years	28	30	58
75-90 Years	12	19	31
Gender, Male/Female [units: Participants]
Female	73	64	137
Male	141	153	294
Race/Ethnicity, Customized [units: Participants] Asian	214	217	431

Outcome Measures

1. Primary Outcome Measure: The Proportion of patients with clinical cure at the test of cure (TOC) visit in the Clinically Evaluable (CE) analysis set. [ Time Frame: At the test of cure visit (Day 28 to35) ]

Measure Type	Primary
Measure Name	The Proportion of patients with clinical cure at the test of cure (TOC) visit in the Clinically Evaluable (CE) analysis set.
Measure Description	The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame	At the test of cure visit (Day 28 to35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The clinically evaluable (CE) analysis set included all patients who met the disease definition of cIAI and met the stringent criteria for clinical evaluation described in the protocol regarding dosing, concomitant medication, evaluation, etc.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	177	184
The Proportion of patients with clinical cure at the test of cure (TOC) visit in the Clinically Evaluable (CE) analysis set. [units: Number of patients]
Clinical cure	166	173
Clinical failure	11	11

Statistical Analysis 1 for The Proportion of patients with clinical cure at the test of cure (TOC) visit in the Clinically Evaluable (CE) analysis set.

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Other [% Risk Difference (RD)]
P-Value^[4]	<0.001
Risk Difference (RD)^[5]	-0.20
95% Confidence Interval	( -5.53 to 4.97 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The Primary objective of this study was to assess the non inferiority (based on a 12.5% margin) of CAZ AVI plus metronidazole compared to meropenem alone with respect to clinical cure at the TOC visit in patients who were CE.
[2]	Additional details about a non-inferiority or equivalence analysis:
	The non-inferiority would be concluded if the lower limit of the 95% confidence interval (CI; corresponding to a 97.5% 1 sided lower bound) was greater than -12.5% for the primary outcome variable.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	RD is CAZ AVI clinical cure rate minus Meropenem clinical cure rate. The CI was calculated by Miettinen and Nurminen method without adjustment.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for 1-sided test at test of cure (TOC) with a -12.5% non-inferiority margin, i.e. H0: diff ≤ -12.5%.
[5]	Other relevant estimation information:
	units for RD are %

2. Secondary Outcome Measure: The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the microbiologically evaluable (ME) analysis set. [ Time Frame: At the end of treatment (EOT) (within 24 hours after last IV dose) ]

Measure Type	Secondary
Measure Name	The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the microbiologically evaluable (ME) analysis set.
Measure Description	The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame	At the end of treatment (EOT) (within 24 hours after last IV dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	106	118
The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the microbiologically evaluable (ME) analysis set. [units: Number of patients]
Clinical cure	103	113
Clinical failure	3	5

No statistical analysis provided for The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the microbiologically evaluable (ME) analysis set.

3. Secondary Outcome Measure: The Proportion of patients with clinical cure at the test of cure (TOC) visit in the microbiologically evaluable (ME) analysis set. [ Time Frame: At the test of cure (TOC) (Day 28 to 35) ]

Measure Type	Secondary
Measure Name	The Proportion of patients with clinical cure at the test of cure (TOC) visit in the microbiologically evaluable (ME) analysis set.
Measure Description	The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame	At the test of cure (TOC) (Day 28 to 35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	99	113
The Proportion of patients with clinical cure at the test of cure (TOC) visit in the microbiologically evaluable (ME) analysis set. [units: Number of patients]
Clinical cure	92	107
Clinical failure	7	6

No statistical analysis provided for The Proportion of patients with clinical cure at the test of cure (TOC) visit in the microbiologically evaluable (ME) analysis set.

4. Secondary Outcome Measure: The Proportion of patients with clinical cure at the late follow up (LFU) visit in the microbiologically evaluable (ME) analysis set. [ Time Frame: At the late follow up (LFU) (Day 42 to 49) ]

Measure Type	Secondary
Measure Name	The Proportion of patients with clinical cure at the late follow up (LFU) visit in the microbiologically evaluable (ME) analysis set.
Measure Description	The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame	At the late follow up (LFU) (Day 42 to 49)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	96	106
The Proportion of patients with clinical cure at the late follow up (LFU) visit in the microbiologically evaluable (ME) analysis set. [units: Number of patients]
Clinical cure	89	100
Clinical failure	7	6

No statistical analysis provided for The Proportion of patients with clinical cure at the late follow up (LFU) visit in the microbiologically evaluable (ME) analysis set.

5. Secondary Outcome Measure: The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the extended microbiologically evaluable (ME) analysis set. [ Time Frame: At the end of treatment (EOT) (within 24 hours after last IV dose) ]

Measure Type	Secondary
Measure Name	The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the extended microbiologically evaluable (ME) analysis set.
Measure Description	The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame	At the end of treatment (EOT) (within 24 hours after last IV dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	107	125
The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the extended microbiologically evaluable (ME) analysis set. [units: Number of patients]
Clinical cure	104	120
Clinical failure	3	5

No statistical analysis provided for The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the extended microbiologically evaluable (ME) analysis set.

6. Secondary Outcome Measure: The Proportion of patients with clinical cure at the test of cure (TOC) visit in the extended microbiologically evaluable (ME) analysis set. [ Time Frame: At the test of cure (TOC) (Day 28 to 35) ]

Measure Type	Secondary
Measure Name	The Proportion of patients with clinical cure at the test of cure (TOC) visit in the extended microbiologically evaluable (ME) analysis set.
Measure Description	The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame	At the test of cure (TOC) (Day 28 to 35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	100	119
The Proportion of patients with clinical cure at the test of cure (TOC) visit in the extended microbiologically evaluable (ME) analysis set. [units: Number of patients]
Clinical cure	93	113
Clinical failure	7	6

No statistical analysis provided for The Proportion of patients with clinical cure at the test of cure (TOC) visit in the extended microbiologically evaluable (ME) analysis set.

7. Secondary Outcome Measure: The Proportion of patients with clinical cure at the late follow up (LFU) visit in the extended microbiologically evaluable (ME) analysis set. [ Time Frame: At the late follow up (LFU) (Day 42 to 49) ]

Measure Type	Secondary
Measure Name	The Proportion of patients with clinical cure at the late follow up (LFU) visit in the extended microbiologically evaluable (ME) analysis set.
Measure Description	The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame	At the late follow up (LFU) (Day 42 to 49)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	97	112
The Proportion of patients with clinical cure at the late follow up (LFU) visit in the extended microbiologically evaluable (ME) analysis set. [units: Number of patients]
Clinical cure	90	106
Clinical failure	7	6

No statistical analysis provided for The Proportion of patients with clinical cure at the late follow up (LFU) visit in the extended microbiologically evaluable (ME) analysis set.

8. Secondary Outcome Measure: The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [ Time Frame: At the end of treatment (EOT) (within 24 hours after last IV dose) ]

Measure Type	Secondary
Measure Name	The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the microbiological modified intent-to-treat (mMITT) analysis set.
Measure Description	The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame	At the end of treatment (EOT) (within 24 hours after last IV dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The microbiological modified intent-to-treat mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	143	152
The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [units: Number of patients]
Clinical cure	126	140
Clinical failure	6	7
Indeterminate	11	5

No statistical analysis provided for The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the microbiological modified intent-to-treat (mMITT) analysis set.

9. Secondary Outcome Measure: The Proportion of patients with clinical cure at the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [ Time Frame: At the test of cure (TOC) (Day 28 to 35) ]

Measure Type	Secondary
Measure Name	The Proportion of patients with clinical cure at the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) analysis set.
Measure Description	The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame	At the test of cure (TOC) (Day 28 to 35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The microbiological modified intent-to-treat mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	143	152
The Proportion of patients with clinical cure at the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [units: Number of patients]
Clinical cure	119	135
Clinical failure	10	9
Indeterminate	14	8

No statistical analysis provided for The Proportion of patients with clinical cure at the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) analysis set.

10. Secondary Outcome Measure: The Proportion of patients with clinical cure at the late follow up (LFU) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [ Time Frame: At the late follow up (LFU) (Day 42 to 49) ]

Measure Type	Secondary
Measure Name	The Proportion of patients with clinical cure at the late follow up (LFU) visit in the microbiological modified intent-to-treat (mMITT) analysis set.
Measure Description	The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame	At the late follow up (LFU) (Day 42 to 49)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The microbiological modified intent-to-treat mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	143	152
The Proportion of patients with clinical cure at the late follow up (LFU) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [units: Number of patients]
Clinical cure	116	132
Clinical failure	10	9
Indeterminate	17	11

No statistical analysis provided for The Proportion of patients with clinical cure at the late follow up (LFU) visit in the microbiological modified intent-to-treat (mMITT) analysis set.

11. Secondary Outcome Measure: The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the clinically evaluable (CE) analysis set. [ Time Frame: At the end of treatment (EOT) (within 24 hours after last IV dose) ]

Measure Type	Secondary
Measure Name	The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the clinically evaluable (CE) analysis set.
Measure Description	The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame	At the end of treatment (EOT) (within 24 hours after last IV dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The clinically evaluable (CE) analysis set included all patients who met the disease definition of cIAI and met the stringent criteria for clinical evaluation described in the protocol regarding dosing, concomitant medication, evaluation, etc.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	190	196
The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the clinically evaluable (CE) analysis set. [units: Number of patients]
Clinical cure	183	187
Clinical failure	7	9

No statistical analysis provided for The Proportion of patients with clinical cure at the end of treatment (EOT) visit in the clinically evaluable (CE) analysis set.

12. Secondary Outcome Measure: The Proportion of patients with clinical cure at the late follow up (LFU) visit in the clinically evaluable (CE) analysis set. [ Time Frame: At late follow up (LFU) visits (Day 42 to 49) ]

Measure Type	Secondary
Measure Name	The Proportion of patients with clinical cure at the late follow up (LFU) visit in the clinically evaluable (CE) analysis set.
Measure Description	The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time Frame	At late follow up (LFU) visits (Day 42 to 49)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The clinically evaluable (CE) analysis set included all patients who met the disease definition of cIAI and met the stringent criteria for clinical evaluation described in the protocol regarding dosing, concomitant medication, evaluation, etc.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	168	179
The Proportion of patients with clinical cure at the late follow up (LFU) visit in the clinically evaluable (CE) analysis set. [units: Number of patients]
Clinical cure	157	168
Clinical failure	11	11

No statistical analysis provided for The Proportion of patients with clinical cure at the late follow up (LFU) visit in the clinically evaluable (CE) analysis set.

13. Secondary Outcome Measure: The proportion of patients with a favorable per-patient microbiological response at the end of treatment (EOT) visit in the microbiologically evaluable (ME) analysis set. [ Time Frame: At the end of treatment (EOT) (within 24 hours after last IV dose) ]

Measure Type	Secondary
Measure Name	The proportion of patients with a favorable per-patient microbiological response at the end of treatment (EOT) visit in the microbiologically evaluable (ME) analysis set.
Measure Description	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame	At the end of treatment (EOT) (within 24 hours after last IV dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	106	118
The proportion of patients with a favorable per-patient microbiological response at the end of treatment (EOT) visit in the microbiologically evaluable (ME) analysis set. [units: Number of patients]
Favorable	103	113
Unfavorable	3	5

No statistical analysis provided for The proportion of patients with a favorable per-patient microbiological response at the end of treatment (EOT) visit in the microbiologically evaluable (ME) analysis set.

14. Secondary Outcome Measure: The proportion of patients with a favorable per-patient microbiological response at the test of cure (TOC) visit in the microbiologically evaluable (ME) analysis set. [ Time Frame: At the test of cure (TOC) (Day 28 to 35) ]

Measure Type	Secondary
Measure Name	The proportion of patients with a favorable per-patient microbiological response at the test of cure (TOC) visit in the microbiologically evaluable (ME) analysis set.
Measure Description	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame	At the test of cure (TOC) (Day 28 to 35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	99	113
The proportion of patients with a favorable per-patient microbiological response at the test of cure (TOC) visit in the microbiologically evaluable (ME) analysis set. [units: Number of patients]
Favorable	92	107
Unfavorable	7	6

No statistical analysis provided for The proportion of patients with a favorable per-patient microbiological response at the test of cure (TOC) visit in the microbiologically evaluable (ME) analysis set.

15. Secondary Outcome Measure: The proportion of patients with a favorable per-patient microbiological response at the late follow up (LFU) visit in the microbiologically evaluable (ME) analysis set. [ Time Frame: At the late follow up (LFU) (Day 42 to 49) ]

Measure Type	Secondary
Measure Name	The proportion of patients with a favorable per-patient microbiological response at the late follow up (LFU) visit in the microbiologically evaluable (ME) analysis set.
Measure Description	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame	At the late follow up (LFU) (Day 42 to 49)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	96	106
The proportion of patients with a favorable per-patient microbiological response at the late follow up (LFU) visit in the microbiologically evaluable (ME) analysis set. [units: Number of patients]
Favorable	89	100
Unfavorable	7	6

No statistical analysis provided for The proportion of patients with a favorable per-patient microbiological response at the late follow up (LFU) visit in the microbiologically evaluable (ME) analysis set.

16. Secondary Outcome Measure: The proportion of patients with a favorable per-patient microbiological response at the end of treatment (EOT) visit in the extended microbiologically evaluable (ME) analysis set. [ Time Frame: At the end of treatment (EOT) (within 24 hours after last IV dose) ]

Measure Type	Secondary
Measure Name	The proportion of patients with a favorable per-patient microbiological response at the end of treatment (EOT) visit in the extended microbiologically evaluable (ME) analysis set.
Measure Description	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame	At the end of treatment (EOT) (within 24 hours after last IV dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	107	125
The proportion of patients with a favorable per-patient microbiological response at the end of treatment (EOT) visit in the extended microbiologically evaluable (ME) analysis set. [units: Number of patients]
Favorable	104	120
Unfavorable	3	5

No statistical analysis provided for The proportion of patients with a favorable per-patient microbiological response at the end of treatment (EOT) visit in the extended microbiologically evaluable (ME) analysis set.

17. Secondary Outcome Measure: The proportion of patients with a favorable per-patient microbiological response at the test of cure (TOC) visit in the extended microbiologically evaluable (ME) analysis set. [ Time Frame: At the test of cure (TOC) (Day 28 to 35) ]

Measure Type	Secondary
Measure Name	The proportion of patients with a favorable per-patient microbiological response at the test of cure (TOC) visit in the extended microbiologically evaluable (ME) analysis set.
Measure Description	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame	At the test of cure (TOC) (Day 28 to 35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	100	119
The proportion of patients with a favorable per-patient microbiological response at the test of cure (TOC) visit in the extended microbiologically evaluable (ME) analysis set. [units: Number of patients]
Favorable	93	113
Unfavorable	7	6

No statistical analysis provided for The proportion of patients with a favorable per-patient microbiological response at the test of cure (TOC) visit in the extended microbiologically evaluable (ME) analysis set.

18. Secondary Outcome Measure: The proportion of patients with a favorable per-patient microbiological response at the late follow up (LFU) visit in the extended microbiologically evaluable (ME) analysis set. [ Time Frame: At the late follow up (LFU) (Day 42 to 49) ]

Measure Type	Secondary
Measure Name	The proportion of patients with a favorable per-patient microbiological response at the late follow up (LFU) visit in the extended microbiologically evaluable (ME) analysis set.
Measure Description	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame	At the late follow up (LFU) (Day 42 to 49)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Extended microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	97	112
The proportion of patients with a favorable per-patient microbiological response at the late follow up (LFU) visit in the extended microbiologically evaluable (ME) analysis set. [units: Number of patients]
Favorable	90	106
Unfavorable	7	6

No statistical analysis provided for The proportion of patients with a favorable per-patient microbiological response at the late follow up (LFU) visit in the extended microbiologically evaluable (ME) analysis set.

19. Secondary Outcome Measure: The proportion of patients with a favorable per-patient microbiological response at the end of treatment (EOT) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [ Time Frame: At the end of treatment (EOT) (within 24 hours after last IV dose) ]

Measure Type	Secondary
Measure Name	The proportion of patients with a favorable per-patient microbiological response at the end of treatment (EOT) visit in the microbiological modified intent-to-treat (mMITT) analysis set.
Measure Description	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame	At the end of treatment (EOT) (within 24 hours after last IV dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The microbiological modified intent-to-treat (mMITT) analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	143	152
The proportion of patients with a favorable per-patient microbiological response at the end of treatment (EOT) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [units: Number of patients]
Favorable	126	140
Unfavorable	6	7
Indeterminate	11	5

20. Secondary Outcome Measure: The proportion of patients with a favorable per-patient microbiological response at the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [ Time Frame: At the test of cure (TOC) (Day 28 to 35) ]

Measure Type	Secondary
Measure Name	The proportion of patients with a favorable per-patient microbiological response at the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) analysis set.
Measure Description	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame	At the test of cure (TOC) (Day 28 to 35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The microbiological modified intent-to-treat (mMITT) analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	143	152
The proportion of patients with a favorable per-patient microbiological response at the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [units: Number of patients]
Favorable	119	135
Unfavorable	10	9
Indeterminate	14	8

No statistical analysis provided for The proportion of patients with a favorable per-patient microbiological response at the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) analysis set.

21. Secondary Outcome Measure: The proportion of patients with a favorable per-patient microbiological response at the late follow up (LFU) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [ Time Frame: At the late follow up (LFU) (Day 42 to 49) ]

Measure Type	Secondary
Measure Name	The proportion of patients with a favorable per-patient microbiological response at the late follow up (LFU) visit in the microbiological modified intent-to-treat (mMITT) analysis set.
Measure Description	Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Time Frame	At the late follow up (LFU) (Day 42 to 49)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The microbiological modified intent-to-treat (mMITT) analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	143	152
The proportion of patients with a favorable per-patient microbiological response at the late follow up (LFU) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [units: Number of patients]
Favorable	116	132
Unfavorable	10	9
Indeterminate	17	11

22. Secondary Outcome Measure: The proportion of favorable per-pathogen microbiological response at the end of treatment (EOT) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [ Time Frame: At the end of treatment (EOT) (within 24 hours after last IV dose) ]

Measure Type	Secondary
Measure Name	The proportion of favorable per-pathogen microbiological response at the end of treatment (EOT) visit in the microbiological modified intent-to-treat (mMITT) analysis set.
Measure Description	The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time Frame	At the end of treatment (EOT) (within 24 hours after last IV dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	143	152
The proportion of favorable per-pathogen microbiological response at the end of treatment (EOT) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [units: Participants with favorable responses]
Escherichia coli (n=84, 89)	77	86
Klebsiella oxytoca (n=5, 5)	5	5
Klebsiella pneumoniae (n=28,35)	22	32
Pseudomonas aeruginosa (n=17, 20)	15	17
Streptococcus anginosus grou (n=8, 7)	7	6
Streptococcus mitis group (n=6, 5)	6	5
Enterococcus faecalis (n=6, 6)	5	5
Enterococcus faecium (n=4, 7)	4	5

No statistical analysis provided for The proportion of favorable per-pathogen microbiological response at the end of treatment (EOT) visit in the microbiological modified intent-to-treat (mMITT) analysis set.

23. Secondary Outcome Measure: The proportion of favorable per-pathogen microbiological response in the microbiological response at the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [ Time Frame: At the test of cure (TOC) (Day 28 to 35) ]

Measure Type	Secondary
Measure Name	The proportion of favorable per-pathogen microbiological response in the microbiological response at the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) analysis set.
Measure Description	The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time Frame	At the test of cure (TOC) (Day 28 to 35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	143	152
The proportion of favorable per-pathogen microbiological response in the microbiological response at the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [units: Participants with favorable responses]
Escherichia coli (n=84, 89)	70	84
Klebsiella oxytoca (n=5, 5)	5	5
Klebsiella pneumoniae (n=28,35)	23	31
Pseudomonas aeruginosa (n=17, 20)	14	17
Streptococcus anginosus group (n=8, 7)	7	5
Streptococcus mitis group (n=6, 5)	6	5
Enterococcus faecalis (n=6, 6)	6	4
Enterococcus faecium (n=4, 7)	4	5

No statistical analysis provided for The proportion of favorable per-pathogen microbiological response in the microbiological response at the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) analysis set.

24. Secondary Outcome Measure: The proportion of favorable per-pathogen microbiological response in the microbiological response at the late follow up (LFU) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [ Time Frame: At the late follow up (LFU) (Day 42 to 49) ]

Measure Type	Secondary
Measure Name	The proportion of favorable per-pathogen microbiological response in the microbiological response at the late follow up (LFU) visit in the microbiological modified intent-to-treat (mMITT) analysis set.
Measure Description	The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time Frame	At the late follow up (LFU) (Day 42 to 49)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	143	152
The proportion of favorable per-pathogen microbiological response in the microbiological response at the late follow up (LFU) visit in the microbiological modified intent-to-treat (mMITT) analysis set. [units: Participants with favorable responses]
Escherichia coli (n=84, 89)	70	82
Klebsiella pneumoniae (n=28, 35)	22	31
Pseudomonas aeruginosa (n=17, 20)	14	17
Klebsiella oxytoca (n=5, 5)	4	5
Enterococcus faecalis (n=6, 6)	4	4
Enterococcus faecium (n=4, 7)	3	5
Streptococcus anginosus group (n=8, 7)	7	5
Streptococcus mitis group (n=6, 5)	6	5

No statistical analysis provided for The proportion of favorable per-pathogen microbiological response in the microbiological response at the late follow up (LFU) visit in the microbiological modified intent-to-treat (mMITT) analysis set.

25. Secondary Outcome Measure: The proportion of favorable per-pathogen microbiological response at the end of treatment (EOT) visit in the microbiologically evaluable (ME) analysis set. [ Time Frame: At the end of treatment (EOT) (within 24 hours after last IV dose) ]

Measure Type	Secondary
Measure Name	The proportion of favorable per-pathogen microbiological response at the end of treatment (EOT) visit in the microbiologically evaluable (ME) analysis set.
Measure Description	The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time Frame	At the end of treatment (EOT) (within 24 hours after last IV dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	99	113
The proportion of favorable per-pathogen microbiological response at the end of treatment (EOT) visit in the microbiologically evaluable (ME) analysis set. [units: Participants with favorable responses]
Escherichia coli (n=69, 77)	68	75
Klebsiella oxytoca (n=5, 5)	5	5
Klebsiella pneumoniae (n=22, 29)	21	28
Pseudomonas aeruginosa (n=14, 16)	14	14

No statistical analysis provided for The proportion of favorable per-pathogen microbiological response at the end of treatment (EOT) visit in the microbiologically evaluable (ME) analysis set.

26. Secondary Outcome Measure: The proportion of favorable per-pathogen microbiological response at the test of cure (TOC) visit in the microbiologically evaluable (ME) analysis set. [ Time Frame: At the test of cure (TOC) (Day 28 to 35) ]

Measure Type	Secondary
Measure Name	The proportion of favorable per-pathogen microbiological response at the test of cure (TOC) visit in the microbiologically evaluable (ME) analysis set.
Measure Description	The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time Frame	At the test of cure (TOC) (Day 28 to 35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	99	113
The proportion of favorable per-pathogen microbiological response at the test of cure (TOC) visit in the microbiologically evaluable (ME) analysis set. [units: Participants with favorable responses]
Escherichia coli (n=69, 77)	64	74
Klebsiella oxytoca (n=5, 5)	5	5
Klebsiella pneumoniae (n=22, 29)	21	28
Pseudomonas aeruginosa (n=14, 16)	13	14

No statistical analysis provided for The proportion of favorable per-pathogen microbiological response at the test of cure (TOC) visit in the microbiologically evaluable (ME) analysis set.

27. Secondary Outcome Measure: The proportion of favorable per-pathogen microbiological response at the late follow up (LFU) visit in the microbiologically evaluable (ME) analysis set. [ Time Frame: At the late follow up (LFU) (Day 42 to 49) ]

Measure Type	Secondary
Measure Name	The proportion of favorable per-pathogen microbiological response at the late follow up (LFU) visit in the microbiologically evaluable (ME) analysis set.
Measure Description	The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time Frame	At the late follow up (LFU) (Day 42 to 49)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	99	113
The proportion of favorable per-pathogen microbiological response at the late follow up (LFU) visit in the microbiologically evaluable (ME) analysis set. [units: Participants with favorable responses]
Escherichia coli (n=69, 77)	63	72
Klebsiella oxytoca (n=5, 5)	4	5
Klebsiella pneumoniae (n=22, 29)	21	27
Pseudomonas aeruginosa (n=14, 16)	13	14

No statistical analysis provided for The proportion of favorable per-pathogen microbiological response at the late follow up (LFU) visit in the microbiologically evaluable (ME) analysis set.

28. Secondary Outcome Measure: The proportion of favorable per-pathogen microbiological response at the end of treatment (EOT) visit in the extended microbiologically evaluable (ME) analysis set. [ Time Frame: At the end of treatment (EOT) (within 24 hours after last IV dose) ]

Measure Type	Secondary
Measure Name	The proportion of favorable per-pathogen microbiological response at the end of treatment (EOT) visit in the extended microbiologically evaluable (ME) analysis set.
Measure Description	The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time Frame	At the end of treatment (EOT) (within 24 hours after last IV dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Extended microbiologically evaluable(ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	100	119
The proportion of favorable per-pathogen microbiological response at the end of treatment (EOT) visit in the extended microbiologically evaluable (ME) analysis set. [units: Participants with favorable responses]
Escherichia coli (n=70, 80)	69	78
Klebsiella oxytoca (n=5, 5)	5	5
Klebsiella pneumoniae (n=22, 30)	21	29
Pseudomonas aeruginosa (n=14, 18)	14	16

No statistical analysis provided for The proportion of favorable per-pathogen microbiological response at the end of treatment (EOT) visit in the extended microbiologically evaluable (ME) analysis set.

29. Secondary Outcome Measure: The proportion of favorable per-pathogen microbiological response at the test of cure (TOC) visit in the extended microbiologically evaluable(ME) analysis set. [ Time Frame: At the test of cure (TOC) (Day 28 to 35) ]

Measure Type	Secondary
Measure Name	The proportion of favorable per-pathogen microbiological response at the test of cure (TOC) visit in the extended microbiologically evaluable(ME) analysis set.
Measure Description	The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time Frame	At the test of cure (TOC) (Day 28 to 35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Extended microbiologically evaluable(ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	100	119
The proportion of favorable per-pathogen microbiological response at the test of cure (TOC) visit in the extended microbiologically evaluable(ME) analysis set. [units: Participants with favorable responses]
Escherichia coli (n=70, 80)	65	77
Klebsiella oxytoca (n=5, 5)	5	5
Klebsiella pneumoniae (n=22, 30)	21	29
Pseudomonas aeruginosa (n=14, 18)	13	16

No statistical analysis provided for The proportion of favorable per-pathogen microbiological response at the test of cure (TOC) visit in the extended microbiologically evaluable(ME) analysis set.

30. Secondary Outcome Measure: The proportion of favorable per-pathogen microbiological response at the late follow up (LFU) visit in the extended microbiologically evaluable (ME) analysis set. [ Time Frame: At the late follow up (LFU) (Day 42 to 49) ]

Measure Type	Secondary
Measure Name	The proportion of favorable per-pathogen microbiological response at the late follow up (LFU) visit in the extended microbiologically evaluable (ME) analysis set.
Measure Description	The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time Frame	At the late follow up (LFU) (Day 42 to 49)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Extended microbiologically evaluable(ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion (summary only shows pathogens where N>/=10)
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	100	119
The proportion of favorable per-pathogen microbiological response at the late follow up (LFU) visit in the extended microbiologically evaluable (ME) analysis set. [units: Participants with favorable responses]
Escherichia coli (n=70, 80)	64	75
Klebsiella oxytoca (n=5, 5)	4	5
Klebsiella pneumoniae (n=22, 30)	21	28
Pseudomonas aeruginosa (n=14, 18)	13	16

No statistical analysis provided for The proportion of favorable per-pathogen microbiological response at the late follow up (LFU) visit in the extended microbiologically evaluable (ME) analysis set.

31. Secondary Outcome Measure: The proportion of patients with a favorable per patient microbiological response at the test of cure (TOC) visit for patients infected with ceftazidime resistant pathogens in the microbiological modified intent-to-treat (mMITT) analysis set. [ Time Frame: At the test of cure (TOC) (Day 28 to 35) ]

Measure Type	Secondary
Measure Name	The proportion of patients with a favorable per patient microbiological response at the test of cure (TOC) visit for patients infected with ceftazidime resistant pathogens in the microbiological modified intent-to-treat (mMITT) analysis set.
Measure Description	The microbiological responses as per the protocoled criteria: responses other than “indeterminate” were classified as “favorable” or “unfavorable.” Favorable microbiological response assessments included “eradication” and “presumed eradication.” Unfavorable microbiological response assessments included “persistence,” “persistence with increasing minimum inhibitory concentration (MIC),” and “presumed persistence.” Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame	At the test of cure (TOC) (Day 28 to 35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The microbiological modified intent-to-treat (mMITT) analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	29	29
The proportion of patients with a favorable per patient microbiological response at the test of cure (TOC) visit for patients infected with ceftazidime resistant pathogens in the microbiological modified intent-to-treat (mMITT) analysis set. [units: Number of patients]
Favorable	24	27
Unfavorable	1	1
Indeterminate	4	1

No statistical analysis provided for The proportion of patients with a favorable per patient microbiological response at the test of cure (TOC) visit for patients infected with ceftazidime resistant pathogens in the microbiological modified intent-to-treat (mMITT) analysis set.

32. Secondary Outcome Measure: The proportion of patients with a favorable per patient microbiological response at the test of cure (TOC) visit for patients infected with ceftazidime resistant pathogens in the microbiologically evaluable (ME) analysis set. [ Time Frame: At the test of cure (TOC) (Day 28 to 35) ]

Measure Type	Secondary
Measure Name	The proportion of patients with a favorable per patient microbiological response at the test of cure (TOC) visit for patients infected with ceftazidime resistant pathogens in the microbiologically evaluable (ME) analysis set.
Measure Description	The microbiological responses as per the protocoled criteria: responses other than “indeterminate” were classified as “favorable” or “unfavorable.” Favorable microbiological response assessments included “eradication” and “presumed eradication.” Unfavorable microbiological response assessments included “persistence,” “persistence with increasing minimum inhibitory concentration (MIC),” and “presumed persistence.” Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame	At the test of cure (TOC) (Day 28 to 35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Microbiologically evaluable (ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture that was susceptible to both treatment groups.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	23	24
The proportion of patients with a favorable per patient microbiological response at the test of cure (TOC) visit for patients infected with ceftazidime resistant pathogens in the microbiologically evaluable (ME) analysis set. [units: Number of patients]
Favorable	22	23
Unfavorable	1	1

33. Secondary Outcome Measure: The proportion of patients with a favorable per patient microbiological response at the test of cure (TOC) visit for patients infected with ceftazidime resistant pathogens in the extended microbiologically evaluable (ME) analysis set. [ Time Frame: At the test of cure (TOC) (Day 28 to 35) ]

Measure Type	Secondary
Measure Name	The proportion of patients with a favorable per patient microbiological response at the test of cure (TOC) visit for patients infected with ceftazidime resistant pathogens in the extended microbiologically evaluable (ME) analysis set.
Measure Description	The microbiological responses as per the protocoled criteria: responses other than “indeterminate” were classified as “favorable” or “unfavorable.” Favorable microbiological response assessments included “eradication” and “presumed eradication.” Unfavorable microbiological response assessments included “persistence,” “persistence with increasing minimum inhibitory concentration (MIC),” and “presumed persistence.” Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time Frame	At the test of cure (TOC) (Day 28 to 35)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Extended microbiologically evaluable(ME) analysis set defined as all patients included in the clinically evaluable (CE) set with at least 1 Gram-negative aerobic pathogen in the initial/prestudy culture regardless of susceptibility.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	23	26
The proportion of patients with a favorable per patient microbiological response at the test of cure (TOC) visit for patients infected with ceftazidime resistant pathogens in the extended microbiologically evaluable (ME) analysis set. [units: Number of patients]
Favorable	22	25
Unfavorable	1	1

No statistical analysis provided for The proportion of patients with a favorable per patient microbiological response at the test of cure (TOC) visit for patients infected with ceftazidime resistant pathogens in the extended microbiologically evaluable (ME) analysis set.

34. Secondary Outcome Measure: The time to first defervescence in the clinically evaluable (CE) analysis set for patients who have fever at study entry. [ Time Frame: while on study therapy (from Day 1 to Day 14) ]

Measure Type	Secondary
Measure Name	The time to first defervescence in the clinically evaluable (CE) analysis set for patients who have fever at study entry.
Measure Description	Time to first defervescence was calculated for patients with a fever (>38ºC) at baseline. Defervescence (≤37.8ºC) was defined as the absence of fever based on the highest temperature recorded on each study day. Time to first defervescence while on IV study therapy in the CE analysis set at TOC for patients who had fever at study entry is defined as time (in days) from the first dose of IV study therapy to first absence of fever.
Time Frame	while on study therapy (from Day 1 to Day 14)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Clinically evaluable (CE) with fever, defined as >38ºC at study entry. No participants were censored at the time of last observation.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	17	26
The time to first defervescence in the clinically evaluable (CE) analysis set for patients who have fever at study entry. [units: Days] Median (Full Range)	1 (1 to 5)	1.5 (1 to 4)

Statistical Analysis 1 for The time to first defervescence in the clinically evaluable (CE) analysis set for patients who have fever at study entry.

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Log Rank
P-Value^[4]	0.773
Other^[5]	0.5

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

35. Secondary Outcome Measure: The time to first defervescence in the microbiological modified intent-to-treat (mMITT) analysis set for patients who have fever at study entry. [ Time Frame: while on study therapy (from Day 1 to Day 14) ]

Measure Type	Secondary
Measure Name	The time to first defervescence in the microbiological modified intent-to-treat (mMITT) analysis set for patients who have fever at study entry.
Measure Description	Time to first defervescence was calculated for patients with a fever (>38ºC) at baseline. Defervescence (≤37.8ºC) was defined as the absence of fever based on the highest temperature recorded on each study day. Time to first defervescence while on IV study therapy in the CE analysis set at TOC for patients who had fever at study entry is defined as time (in days) from the first dose of IV study therapy to first absence of fever.
Time Frame	while on study therapy (from Day 1 to Day 14)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
microbiological modified intent-to-treat (mMITT) with fever, defined as >38ºC at study entry. No participants were censored at the time of last observation.

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	16	26
The time to first defervescence in the microbiological modified intent-to-treat (mMITT) analysis set for patients who have fever at study entry. [units: Days] Median (Full Range)	1 (1 to 5)	2 (1 to 4)

Statistical Analysis 1 for The time to first defervescence in the microbiological modified intent-to-treat (mMITT) analysis set for patients who have fever at study entry.

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Log Rank
P-Value^[4]	0.598
Other^[5]	1

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

36. Secondary Outcome Measure: Safety and tolerability by incidence and severity of adverse events and serious adverse events and mortality. [ Time Frame: study duration (from screening to Day 49 LFU visit) ]

Measure Type	Secondary
Measure Name	Safety and tolerability by incidence and severity of adverse events and serious adverse events and mortality.
Measure Description	Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42).
Time Frame	study duration (from screening to Day 49 LFU visit)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set: all patients who received at least 1 dose of IP

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	215	217
Safety and tolerability by incidence and severity of adverse events and serious adverse events and mortality. [units: Number of patients]
Any AE	82	83
Any SAE	9	11
Any AE leading to discontinuation of IP	7	3
Any AE of severe intensity	5	5
Total number of deaths	2	1
Deaths due to disease progression	2	0
Any AE with outcome=death	0	1

No statistical analysis provided for Safety and tolerability by incidence and severity of adverse events and serious adverse events and mortality.

37. Secondary Outcome Measure: Safety and tolerability by incidence: Extent of exposure. [ Time Frame: study duration (from screening to Day 49 LFU visit) ]

Measure Type	Secondary
Measure Name	Safety and tolerability by incidence: Extent of exposure.
Measure Description	Duration of exposure is calculated as the difference between the last study therapy date and the first study therapy date converted to days plus 1 day. Actual calculated duration could be shorter or longer than a full day.
Time Frame	study duration (from screening to Day 49 LFU visit)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set: all patients who received at least 1 dose of IP

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	215	217
Safety and tolerability by incidence: Extent of exposure. [units: Number of patients]
1 - 2 days	10	5
3 - 4 days	6	5
5 -10 days	175	181
11 - 14 days	24	26
>14 days	0	0

No statistical analysis provided for Safety and tolerability by incidence: Extent of exposure.

38. Secondary Outcome Measure: Safety and tolerability: Clinical laboratory evaluation hematology. [ Time Frame: study duration (from screening to Day 49 LFU visit) ]

Measure Type	Secondary
Measure Name	Safety and tolerability: Clinical laboratory evaluation hematology.
Measure Description	Potentially clinically significant (PCS) post Baseline hematology values up to LFU (Safety analysis set)
Time Frame	study duration (from screening to Day 49 LFU visit)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set: all patients who received at least 1 dose of IP

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	215	217
Safety and tolerability: Clinical laboratory evaluation hematology. [units: Number of patients]
Platelet count: PCS (Low)	1	1
Platelet count: PCS (High)	5	4
Red blood cell count: PCS (Low)	7	13
Red blood cell count: PCS (High)	0	0
White blood cell: PCS (Low)	1	1
White blood cell: PCS (High)	4	5
Hemoglobin: PCS (Low)	7	14
Hemoglobin: PCS (High)	0	0
Lymphocytes: PCS (Low)	1	1
Lymphocytes: PCS (High)	0	1
Neutrophils: PCS (Low)	4	2
Neutrophils: PCS (High)	9	8
Eosinophils: PCS (High)	0	0
Monocytes: PCS (High)	0	0
Basophils: PCS (High)	0	0
Direct Coombs test:- at Baseline, + post-Baseline	15	2
Hematocrit (ratio): PCS (Low)	5	8
Hematocrit (ratio): PCS (High)	0	0

No statistical analysis provided for Safety and tolerability: Clinical laboratory evaluation hematology.

39. Secondary Outcome Measure: Safety and tolerability: Clinical laboratory evaluation clinical chemistry. [ Time Frame: study duration (from screening to Day 49 LFU visit) ]

Measure Type	Secondary
Measure Name	Safety and tolerability: Clinical laboratory evaluation clinical chemistry.
Measure Description	Potentially clinically significant (PCS) post Baseline clinical chemistry values up to LFU (Safety analysis set)
Time Frame	study duration (from screening to Day 49 LFU visit)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set: all patients who received at least 1 dose of IP

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	215	217
Safety and tolerability: Clinical laboratory evaluation clinical chemistry. [units: Number of patients]
Alanine aminotransferase (μkat/L): PCS (High)	3	8
Alkaline phosphatase (μkat/L): PCS (Low)	0	0
Alkaline phosphatase (μkat/L): PCS (High)	2	3
Aspartate aminotransferase (μkat/L): PCS (High)	4	4
Bicarbonate (mmol/L) PCS (Low)	1	0
Bicarbonate (mmol/L): PCS (High)	0	0
Creatinine (μmol/L): PCS (High)	0	1
Glucose (non-fasting) (mmol/L): PCS (Low)	0	0
Glucose (non-fasting) (mmol/L): PCS (High)	1	1
Gamma-glutamyl transferase (μkat/L):PCS (High)	2	4
Inorganic phosphorus (mmol/L): PCS (Low)	3	7
Inorganic phosphorus (mmol/L): PCS (High)	0	0
Potassium (mmol/L): PCS (Low)	9	5
Potassium (mmol/L): PCS (High)	3	1
Total bilirubin (μmol/L): PCS (High)	0	1
Direct bilirubin (μmol/L): PCS (High)	1	1

No statistical analysis provided for Safety and tolerability: Clinical laboratory evaluation clinical chemistry.

40. Secondary Outcome Measure: Safety and tolerability:ECG , QTcB and QTcF intervals [ Time Frame: EOT visit/any observation on treatment ]

Measure Type	Secondary
Measure Name	Safety and tolerability:ECG , QTcB and QTcF intervals
Measure Description	Shifts in ECG interpretation and changes in QT, QTcB, and QTcF intervals , from baseline to post baseline.
Time Frame	EOT visit/any observation on treatment
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set: all patients who received at least 1 dose of IP

Reporting Groups

	Description
Ceftazidime-Avibactam plus metronidazole	Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg Plus Metronidazole 500mg/100ml solution for infusion
Meropenem	Meropenem powder for solution for infusion 1000mg

Measured Values

	Ceftazidime-Avibactam plus metronidazole	Meropenem
Number of Participants Analyzed [units:participants]	215	217
Safety and tolerability:ECG , QTcB and QTcF intervals [units: Number of patients]
Normal to Abnormal: EOT	17	14
Normal to Abnormal: Anytime up to EOT	34	30
Reaching a value in QT: ≥450 (ms)	9	10
Reaching a value in QT: ≥480 (ms)	2	1
Reaching a value in QT: ≥500 (ms)	0	0
QT: ≥500 and increase from Baseline ≥60(ms)	0	0
Increase in QT: ≥30 (ms)	115	114
Increase in QT: ≥60 (ms)	50	44
Decrease in QT: ≥30 (ms)	24	24
Decrease in QT: ≥60 (ms)	12	4
Reaching a value in QTcB: ≥450(ms)	57	63
Reaching a value in QTcB: ≥480(ms)	13	8
Reaching a value in QTcB: ≥500 (ms)	4	2
QTcB: ≥500 and increase from Baseline ≥60(ms)	2	1
Increase in QTcB: ≥30 (ms)	21	27
Increase in QTcB: ≥60 (ms)	2	1
Decrease in QTcB: ≥30 (ms)	42	26
Decrease in QTcB: ≥60 (ms)	6	4
Reaching a value in QTcF: ≥450 (ms)	19	18
Reaching a value in QTcF: ≥480 (ms)	4	0
Reaching a value in QTcF: ≥500 (ms)	1	0
QTcF: ≥500 and increase from Baseline ≥60 (ms)	0	0
Increase in QTcF: ≥30 (ms)	42	41
Increase in QTcF: ≥60 (ms)	4	3
Decrease QTcF: ≥30 (ms)	21	19
Decrease QTcF: ≥60 (ms)	7	1

No statistical analysis provided for Safety and tolerability:ECG , QTcB and QTcF intervals

41. Secondary Outcome Measure: Plasma concentrations for ceftazidime and avibactam [ Time Frame: At Day 3: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug. ]

Measure Type	Secondary
Measure Name	Plasma concentrations for ceftazidime and avibactam
Measure Description	Blood samples were taken from all patients on Day 3 for the pharmacokinetic evaluation of ceftazidime and avibactam plasma concentrations
Time Frame	At Day 3: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK analysis set

Reporting Groups

	Description
Ceftazidime(1)	15 minutes before or after
Avibactam(1)	15 minutes before or after
Ceftazidime(2)	30-90 minutes after
Avibactam(2)	30-90 minutes after
Ceftazidime(3)	300-360 minutes after
Avibactam(3)	300-360 minutes after

Measured Values

	Ceftazidime(1)	Avibactam(1)	Ceftazidime(2)	Avibactam(2)	Ceftazidime(3)	Avibactam(3)
Number of Participants Analyzed [units:participants]	195	195	193	193	192	192
Plasma concentrations for ceftazidime and avibactam [units: ng/mL] Geometric Mean (Full Range)	60300.4 (1390 to 1880000)	10126.9 (197 to 435000)	46473.9 (2080 to 210000)	7289.3 (229 to 36300)	9555.0 (1740 to 222000)	1207.2 (227 to 36300)

No statistical analysis provided for Plasma concentrations for ceftazidime and avibactam

Serious Adverse Events

Time Frame	Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary.
Additional Description	AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.

Reporting Groups

	Description
CAZ-AVI plus Metronidazole	No text entered.
Meropenem	Meropenem powder for solution for infusion 1000mg

Serious Adverse Events

CAZ-AVI plus Metronidazole

Meropenem

Total, serious adverse events

# participants affected / at risk

9/215 (4.19%)

11/217 (5.07%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

1/215 (0.47%)

0/217 (0.00%)

# events

Cardiac disorders

Arteriosclerosis coronary artery¹,^†

# participants affected / at risk

1/215 (0.47%)

0/217 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain lower¹,^†

# participants affected / at risk

1/215 (0.47%)

0/217 (0.00%)

# events

Gastrointestinal disorders

Gastric ulcer¹,^†

# participants affected / at risk

0/215 (0.00%)

1/217 (0.46%)

# events

Gastrointestinal disorders

Gastritis¹,^†

# participants affected / at risk

1/215 (0.47%)

0/217 (0.00%)

# events

Gastrointestinal disorders

Ileus¹,^†

# participants affected / at risk

0/215 (0.00%)

1/217 (0.46%)

# events

General disorders and administration site conditions

Impaired healing¹,^†

# participants affected / at risk

0/215 (0.00%)

1/217 (0.46%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

0/215 (0.00%)

1/217 (0.46%)

# events

Hepatobiliary disorders

Cholangitis acute¹,^†

# participants affected / at risk

1/215 (0.47%)

0/217 (0.00%)

# events

Hepatobiliary disorders

Hepatic function abnormal¹,^†

# participants affected / at risk

1/215 (0.47%)

0/217 (0.00%)

# events

Infections and infestations

Abdominal infection¹,^†

# participants affected / at risk

1/215 (0.47%)

0/217 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

0/215 (0.00%)

1/217 (0.46%)

# events

Infections and infestations

Postoperative wound infection¹,^†

# participants affected / at risk

1/215 (0.47%)

1/217 (0.46%)

# events

Injury, poisoning and procedural complications

Incision site complication¹,^†

# participants affected / at risk

0/215 (0.00%)

1/217 (0.46%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastasis¹,^†

# participants affected / at risk

1/215 (0.47%)

0/217 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-Hodgkin's lymphoma¹,^†

# participants affected / at risk

0/215 (0.00%)

1/217 (0.46%)

# events

Psychiatric disorders

Confusional state¹,^†

# participants affected / at risk

0/215 (0.00%)

1/217 (0.46%)

# events

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

1/215 (0.47%)

1/217 (0.46%)

# events

Respiratory, thoracic and mediastinal disorders

Acute respiratory distress syndrome¹,^†

# participants affected / at risk

1/215 (0.47%)

0/217 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Laryngeal disorder¹,^†

# participants affected / at risk

1/215 (0.47%)

0/217 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonia aspiration¹,^†

# participants affected / at risk

0/215 (0.00%)

1/217 (0.46%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 18.0

Other Adverse Events

Time Frame	Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42). FOR SAE's - only those reported by 2 or more patients in either group are shown in this summary.
Additional Description	AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.

Frequency Threshold

Threshold above which other adverse events are reported	2%

Reporting Groups

	Description
CAZ-AVI plus Metronidazole	No text entered.
Meropenem	Meropenem powder for solution for infusion 1000mg

Other Adverse Events

CAZ-AVI plus Metronidazole

Meropenem

Total, other (not including serious) adverse events

# participants affected / at risk

44/215 (20.47%)

47/217 (21.66%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

5/215 (2.33%)

3/217 (1.38%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

13/215 (6.05%)

16/217 (7.37%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

18/215 (8.37%)

4/217 (1.84%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

5/215 (2.33%)

4/217 (1.84%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

9/215 (4.19%)

12/217 (5.53%)

# events

Hepatobiliary disorders

Hepatic function abnormal¹,^†

# participants affected / at risk

0/215 (0.00%)

6/217 (2.76%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

3/215 (1.40%)

5/217 (2.30%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

3/215 (1.40%)

8/217 (3.69%)

# events

Respiratory, thoracic and mediastinal disorders

Productive cough¹,^†

# participants affected / at risk

5/215 (2.33%)

6/217 (2.76%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 18.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The investigator agrees not to use such Confidential study information and not to disclose them to any other third parties, except that the undersigned shall not be prevented from using or disclosing information: (a) which by written records was previously known; (b) which is now public knowledge, (c) which is lawfully obtained by the undersigned from sources who have a lawful right to disclose such information.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	David Wilson, Statistical Team Leader - Infection
Organization:	AstraZeneca
Phone	+44 1625 517830
E-mail:	[email protected]

Documents available

Protocol redacted
Download
Protocol Amendment 1 redacted
Download
Protocol Amendment 3 redacted
Download
Protocol Amendment 2 redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Paul A Newell

AstraZeneca LP

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site