Candesartan Effectiveness study in Pro-B Type Natriuretic Peptides (BNP)

Study identifier:D2452L00012

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A multicenter, non-comparative, phase IV study to evaluate the effect of candesartan based therapy in the percent change of proBNP level after 24 week treatment in the patients with hypertension with left ventricular hypertrophy

Medical condition

hypertension

Phase

Phase 4

Healthy volunteers

Study drug

Candesartan, Felodipine

Sex

All

Actual Enrollment

315

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 01 Jun 2006

Primary Completion Date: 01 Jun 2008

Study Completion Date: 01 Jun 2008

Study design

Allocation: Non-randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2012 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

DaeGu, Republic of Korea

Location

Research Site

BuSan, Republic of Korea

Location

Research Site

KwangJu, Republic of Korea

Location

Research Site

JeonJu, Republic of Korea

Location

Research Site

DaeJeon, Republic of Korea

Location

Research Site

CheonAn, Republic of Korea

Location

Research Site

CheongJu, Republic of Korea

Location

Research Site

Chunbuk, Republic of Korea

Arms	Assigned Interventions
Experimental: Candesartan Subjects were treated for 24 weeks with Candesartan 16mg once daily as initial dose. Subjects were modified investigational product dose to Candesartan 32mg, Candesartan 32mg + Felodipine 5mg, Candesartan 32mg + Felodipine 10mg, sequentially according to their blood pressures.	Drug: Candesartan 16 mg once daily in oral tablet form Other Name: Atacand Drug: Candesartan 32 mg once daily in oral tablet form Other Name: Antacand Drug: Felodipine 5 mg once daily in oral tablet form Drug: Felodipine 10 mg once daily in oral tablet form

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Milestone date: 15 June 2006 (FSI) ~ 05 June 2008 (LSLV) Type of location: General Hospital; 333 subjects enrolled, but 18 subjects failed to be randomized, 315 subjects were randomized to study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screening period: Laboratory test (Creatinine, potassium, ALT, etc)

Reporting Groups

	Description
Candesartan	Subjects were treated for 24 weeks with Candesartan 16mg once daily as initial dose. Subjects were modified investigational product dose to Candesartan 32mg, Candesartan 32mg + Felodipine 5mg, Candesartan 32mg + Felodipine 10mg, sequentially according to their blood pressures.

Participant Flow: Overall Study

	Candesartan
STARTED	315
COMPLETED	249
NOT COMPLETED	66
Withdrawal by Subject	45
Adverse Event	5
Protocol Violation	6
Lost to Follow-up	2
Multiple Reasons	8

Baseline Characteristics

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

Reporting Groups

	Description
Candesartan

Baseline Measures

	Candesartan
Number of Participants [units: Participants]	315
Age Continuous [units: years] Mean ± Standard Deviation	49.90 ± 11.9
GenderNIH [units: Participants]
Female	81
Male	234

Outcome Measures

1. Primary Outcome Measure: Percent Change of B Type Natriuretic Peptides (BNP) Level [ Time Frame: At Baseline and 24 weeks ]

Measure Type	Primary
Measure Name	Percent Change of B Type Natriuretic Peptides (BNP) Level
Measure Description	Change of B Type Natriuretic Peptides Level of the Subjects With Hypertension and Left Ventricular Hypertrophy (LVH) Treated With Candesartan Based Therapy for 24 Weeks was calculated just as the later time point minus the earlier time point. No specific calculation was used.
Time Frame	At Baseline and 24 weeks
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.
Followed Intent-to-treat analysis

Reporting Groups

	Description
Candesartan	Subjects were treated for 24 weeks with Candesartan 16mg once daily as initial dose. Subjects were modified investigational product dose to Candesartan 32mg, Candesartan 32mg + Felodipine 5mg, Candesartan 32mg + Felodipine 10mg, sequentially according to their blood pressures.

Measured Values

	Candesartan
Number of Participants Analyzed [units:participants]	292
Percent Change of B Type Natriuretic Peptides (BNP) Level [units: Percent Change] Median (Full Range)	-29.2 (-35.3 to -16.7)

No statistical analysis provided for Percent Change of B Type Natriuretic Peptides (BNP) Level

2. Secondary Outcome Measure: LVH(Left Ventricular Hypertrophy) regression by echocardiac parameter, left ventricular mass index [ Time Frame: At Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	LVH(Left Ventricular Hypertrophy) regression by echocardiac parameter, left ventricular mass index
Measure Description	Change of Left Ventricular Hypertrophy(LVH) by Echocardiac Parameter, Left Ventricular mass Index (LVMI) was calculated and collected through the way of Last Observational carried forward. LVH/Index was calculated like this: Divide LV mass with Body Surface Area.
Time Frame	At Baseline and 24 weeks
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.
Only 245 patients who have reliable Echocardiac data were analyzed.

Reporting Groups

	Description
Candesartan	Subjects were treated for 24 weeks with Candesartan 16mg once daily as initial dose. Subjects were modified investigational product dose to Candesartan 32mg, Candesartan 32mg + Felodipine 5mg, Candesartan 32mg + Felodipine 10mg, sequentially according to their blood pressures.

Measured Values

	Candesartan
Number of Participants Analyzed [units:participants]	245
LVH(Left Ventricular Hypertrophy) regression by echocardiac parameter, left ventricular mass index [units: g/m^2] Median (Full Range)	-10.90 (-14.00 to -7.0)

No statistical analysis provided for LVH(Left Ventricular Hypertrophy) regression by echocardiac parameter, left ventricular mass index

3. Secondary Outcome Measure: Change of Systolic Blood Pressure (SBP) [ Time Frame: At Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	Change of Systolic Blood Pressure (SBP)
Measure Description	Change of Systolic Blood Pressure was calculated and collected through the way of Last Observational carried forward.
Time Frame	At Baseline and 24 weeks
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.
Only who has systolic blood pressure data both baseline and follow up was analyzed. Most of patient who enrolled, 302 have a data.

Reporting Groups

	Description
Candesartan	Subjects were treated for 24 weeks with Candesartan 16mg once daily as initial dose. Subjects were modified investigational product dose to Candesartan 32mg, Candesartan 32mg + Felodipine 5mg, Candesartan 32mg + Felodipine 10mg, sequentially according to their blood pressures.

Measured Values

	Candesartan
Number of Participants Analyzed [units:participants]	302
Change of Systolic Blood Pressure (SBP) [units: mmHg] Median (Full Range)	-32.0 (-35.0 to -30.0)

No statistical analysis provided for Change of Systolic Blood Pressure (SBP)

4. Secondary Outcome Measure: Change of Diastolic Blood Pressure (DBP) [ Time Frame: At Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	Change of Diastolic Blood Pressure (DBP)
Measure Description	Change of Diastolic Blood Pressure was calculated and collected through the way of Last Observational carried forward. Only who has diastolic blood pressure data both baseline and follow up was analyzed. Most of patient who enrolled, 302 have a data.
Time Frame	At Baseline and 24 weeks
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.
Last Observational carried forward

Reporting Groups

	Description
Candesartan	Subjects were treated for 24 weeks with Candesartan 16mg once daily as initial dose. Subjects were modified investigational product dose to Candesartan 32mg, Candesartan 32mg + Felodipine 5mg, Candesartan 32mg + Felodipine 10mg, sequentially according to their blood pressures.

Measured Values

	Candesartan
Number of Participants Analyzed [units:participants]	302
Change of Diastolic Blood Pressure (DBP) [units: mmHg] Median (Full Range)	-20.0 (-20.0 to -18.0)

No statistical analysis provided for Change of Diastolic Blood Pressure (DBP)

5. Secondary Outcome Measure: Percent Change of proBNP(B type Natriuretic Peptides) in Patients Treated With Candesartan Only [ Time Frame: At Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	Percent Change of proBNP(B type Natriuretic Peptides) in Patients Treated With Candesartan Only
Measure Description	Percent change of proBNP(B type Natriuretic Peptides) was calculated and collected through the way of Last Observational carried forward.
Time Frame	At Baseline and 24 weeks
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.
Only 201 patients are available for analysis.

Reporting Groups

	Description
Candesartan	Subjects were treated for 24 weeks with Candesartan 16mg once daily as initial dose. Subjects were modified investigational product dose to Candesartan 32mg, Candesartan 32mg + Felodipine 5mg, Candesartan 32mg + Felodipine 10mg, sequentially according to their blood pressures.

Measured Values

	Candesartan
Number of Participants Analyzed [units:participants]	201
Percent Change of proBNP(B type Natriuretic Peptides) in Patients Treated With Candesartan Only [units: percent change] Median (Full Range)	-18.9 (-33.0 to -6.6)

No statistical analysis provided for Percent Change of proBNP(B type Natriuretic Peptides) in Patients Treated With Candesartan Only

6. Secondary Outcome Measure: Percent Change of proBNP(B type natriuretic peptides) in Patients With Candesartan Plus Felodipine [ Time Frame: At Baseline and 24 weeks ]

Measure Type	Secondary
Measure Name	Percent Change of proBNP(B type natriuretic peptides) in Patients With Candesartan Plus Felodipine
Measure Description	Percent change of proBNP(B type Natriuretic Peptides) was calculated and collected through the way of Last Observational carried forward.
Time Frame	At Baseline and 24 weeks
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.
Only 91 patients are available for analysis

Reporting Groups

	Description
Candesartan	Subjects were treated for 24 weeks with Candesartan 16mg once daily as initial dose. Subjects were modified investigational product dose to Candesartan 32mg, Candesartan 32mg + Felodipine 5mg, Candesartan 32mg + Felodipine 10mg, sequentially according to their blood pressures.

Measured Values

	Candesartan
Number of Participants Analyzed [units:participants]	91
Percent Change of proBNP(B type natriuretic peptides) in Patients With Candesartan Plus Felodipine [units: percent change] Median (Full Range)	-36.1 (-57.9 to -24.3)

No statistical analysis provided for Percent Change of proBNP(B type natriuretic peptides) in Patients With Candesartan Plus Felodipine

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Candesartan	No text entered.

Serious Adverse Events

Candesartan

Total, serious adverse events

# participants affected / at risk

8/---

Gastrointestinal disorders

Left paraduodenal hernia¹,^†

# participants affected / at risk

1/---

Gastrointestinal disorders

Rectal prolapse aggravated¹,^†

# participants affected / at risk

1/---

Vascular disorders

Cerebral infarction¹,^†

# participants affected / at risk

1/---

Renal and urinary disorders

Uterine myoma aggravated¹,^†

# participants affected / at risk

1/---

General disorders

Cervical disc herniation aggravated¹,^†

# participants affected / at risk

1/---

Respiratory, thoracic and mediastinal disorders

Pneumonia with effusion in the right chest¹,^†

# participants affected / at risk

1/---

Skin and subcutaneous tissue disorders

Granuloma inguinale¹,^†

# participants affected / at risk

1/---

Cardiac disorders

Acute myocardial infarction¹,^†

# participants affected / at risk

1/---

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Candesartan	No text entered.

Other Adverse Events

Candesartan

Total, other (not including serious) adverse events

# participants affected / at risk

37/---

Nervous system disorders

Headache¹,^†

# participants affected / at risk

23/---

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

16/---

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	Term from vocabulary,

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:

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:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=305&filename=CSR-D2452L00012.pdf
Download
CSR-D2452L00012.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Korea Clinical Study Information

+ 82 2 2188 0872

nayoung.lee@astrazeneca.com

Investigators

Principal Investigator

JeeWoong Son

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=305&filename=CSR-D2452L00012.pdf

CSR-D2452L00012.pdf

Trial Results Summaries