Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE I)

Official Title: “A Parallel Randomized Controlled Evaluation of Clopidogrel Plus Aspirin, With Factorial Evaluation of Irbesartan, for the Prevention of Vascular Events, in Patients With Atrial Fibrillation”

The purpose of this study was to determine if Irbesartan compared to Placebo would reduce the risk of vascular events such as heart attack, stroke, non-cerebral thromboembolic event and death in patients with Atrial Fibrillation (AF) and with at least one major risk of vascular events.

ACTIVE I was one of the 3 separate but related trials of the ACTIVE program conducted in AF patients at risk of vascular events.

Patients were enrolled first into one of the 2 parallel trials of the ACTIVE program evaluating Clopidogrel: - ACTIVE A comparing clopidogrel + acetylsalicylic acid (ASA) and ASA alone - ACTIVE W comparing clopidogrel + ASA and oral anticoagulant (OAC).

Then those satisfying additional criteria related to blood pressure and angiotensin receptor blocking agents were re-randomized in the two ACTIVE I arms according to a separate randomization list.

Intervention(s) in this Clinical Trial

• Drug: Irbesartan
  • oral administration (tablets) once daily
• Drug: placebo
  • oral administration (tablets) once daily

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Irbesartan
  • 150 mg for 2 weeks, then up-titrated to 300 mg up to final follow-up visit
• Placebo Comparator: Placebo
  • Matching placebo up to final follow-up visit

Primary Measures

• First Occurence of Any Component of the Composite of Myocardial Infarction, Stroke or Vascular Death as Per Adjudication
  • Time Frame: Median follow-up of 4.5 years
    Safety Issue?: No
• First Occurence of Any Component of the Composite of Myocardial Infarction, Stroke, Vascular Death or Hospitalization for Heart Failure as Per Adjudication
  • Time Frame: Median follow-up of 4.5 years
    Safety Issue?: No

Secondary Measures

• First Occurrence of Stroke
  • Time Frame: Median follow-up of 4.5 years
    Safety Issue?: No
• Death From Any Cause
  • Time Frame: Median follow-up of 4.5 years
    Safety Issue?: No
• First Occurrence of Any Heart Failure (HF) Episode
  • Time Frame: Median follow-up of 4.5 years
    Safety Issue?: No
• First Hospitalisation for Heart Failure (HF)
  • Time Frame: Median follow-up of 4.5 years
    Safety Issue?: No
• First Hospitalisation for Other Cardiovascular (CV) Cause
  • Time Frame: Median follow-up of 4.5 years
    Safety Issue?: No

Inclusion Criteria:

Should fulfill the eligibility criteria for ACTIVE A or ACTIVE W trial and:

• have a systolic blood pressure of at least 110 mmHg
• not already receiving an angiotensin receptor blocking agent, unless they are willing and able to be changed to another antihypertensive agent
• no previous intolerance to angiotensin receptor blocking agents
• no proven indication for angiotensin receptor blocking agents, unless an Angiotensin
• Converting Enzyme (ACE) inhibitor can be substituted

Exclusion Criteria:

Patients will be excluded from ACTIVE study if any of the following are present:

• requirement for clopidogrel (such as recent coronary stent procedure)
• requirement for oral anticoagulant (such as prosthetic mechanical heart valve)
• prior intolerance to acetylsalicyclic acid (ASA) or clopidogrel
• documented peptic ulcer disease within the previous 6 months
• prior intracerebral hemorrhage
• significant thrombocytopenia (platelet count <50 x 10(9)/L)
• psychosocial reason making study participation impractical
• geographic reason making study participation impractical
• ongoing alcohol abuse
• mitral stenosis
• pregnant or nursing woman or woman of child bearing potential and not on effective birth control for at least one month prior to start of study or not willing to continue on birth control for duration of study
• severe comorbid condition such that the patient is not expected to survive 6 months
• patient currently receiving an investigational pharmacologic agent
• requirement for chronic (> 3 months) non-cyclooxygenase-2 (non-COX-2) inhibitor nonsteroidal anti-inflammatory drug (NSAID) therapy unless willing enrolled in ACTIVE
A

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Sanofi-Aventis Industry

Overall Clinical Trial Officials and Contacts

Salim YUSUF, Prof. Study Chair Hamilton Health Sciences Corporation  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00249795

Study ID Number: EFC4912 I

ClinicalTrials.gov Identifier: NCT00249795

Health Authority: United States: Food and Drug Administration