AZD8601 study in CABG patients

Exclusion Criteria

• Patients should not enter the study if any of the following exclusion criteria are fulfilled:
• 1. Involvement in the planning and/or conduct of the study (applies to both
• AstraZeneca staff and/or staff at the study site)
• 2. Previous randomisation in the present study
• 3. Participation in another clinical study with an investigational product during the last
• 3 months
• 4. BMI > 35 kg/m2 OR poor image window for echocardiography
• 5. Need for CABG emergency operation. (Emergency operation is defined as
• significant symptom status worsening in CAD, such as crescendo angina, unstable angina or ACS requiring rescheduling the revascularization. CAD should be stable at least 3 months prior to Visit 3.)
• 6. History of ventricular arrhythmia (≥ Lown III) without Implantable Cardiac Defibrillator (ICD) History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the patient at risk because of participation in the study, or
• influence the results or the patient’s ability to participate in the study
• 8. Severe co-morbidities that can interfere with the execution of the study, interpretation of study results or affect the safety of the patient, in judgement of the investigator
• 9. eGFR ≤ 30 mL/min (derived from creatinine clearance, calculated by local lab)
• 10. For CFVR (Visit 1) and sMBF (Visit 2) measurement:
• - Known severe adverse reactions to adenosine
• - Known elevated intracranial pressure
• - AV block ≥ second degree and/or sick sinus syndrome in patient without pacemaker
• - Heart rate < 40 bpm (ECG verified)
• - Systolic blood pressure < 90 mmHg
• - Asthma or COPD with strong reactive component in judgement of investigator
• - Treatment with dipyridamole (e.g. Persantin or Asasantin), theophyllamine or fluvoxamine that cannot be paused
• 11. Inability to comply with the protocol
• 12. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar chemical structure or class as study drugs
• 13. Patients unable to give their consent or communicate reliably with the investigator or vulnerable patients e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order
• 14. Positive hepatitis C antibody hepatitis B virus surface antigen or hepatitis B virus core antibody or human immunodeficiency virus, at Visit 1
• 15. Known history of drug or alcohol abuse
• 16. Any concomitant medications that are known to be associated with Torsades de Pointes
• 17. History of QT prolongation associated with other medications that required discontinuation of that medication
• 18. Congenital long QT syndrome
• 19. History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3).
• 20. Current atrial fibrillation as well as paroxysmal atrial fibrillation.