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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Atrial Fibrillation, Cardiovascular Disease

Intervention / Treatment
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* Drug: Irbesartan
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Irbesartan<br>150 mg for 2 weeks, then up-titrated to 300 mg up to final follow-up visit | Drug: Irbesartan<br>* oral administration (tablets) once daily<br>* Other names: Aprovel®;|
| Placebo Comparator: Placebo<br>Matching placebo up to final follow-up visit | Drug: placebo<br>* oral administration (tablets) once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First Occurence of Any Component of the Composite of Myocardial Infarction, Stroke or Vascular Death as Per Adjudication | The first co-primary event is the first occurence of any component of the following cluster over the duration of follow-up: myocardial infarction (nonfatal or fatal), stroke (nonfatal or fatal) or vascular death - after validation by the Event Adjudication Committee (EAC). | Median follow-up of 4.5 years | 
| First Occurence of Any Component of the Composite of Myocardial Infarction, Stroke, Vascular Death or Hospitalization for Heart Failure as Per Adjudication | The second co-primary event is the first occurence of any component of the following cluster over the duration of follow-up: myocardial infarction (nonfatal or fatal), stroke (nonfatal or fatal), vascular death or hospitalization for heart failure - after validation by the EAC. | Median follow-up of 4.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First Occurrence of Stroke | The considered event is the first occurrence of stroke (nonfatal or fatal, ischemic, hemorrhagic or of uncertain type) over the duration of follow-up, after validation by the EAC. | Median follow-up of 4.5 years | 
| Death From Any Cause | The considered event is the death over the duration of the follow-up whatever the cause, cardiovascular or non-cardiovascular. | Median follow-up of 4.5 years | 
| First Occurrence of Any Heart Failure (HF) Episode | The considered event is the first occurence of any HF episode defined as evidence of signs and symptoms of HF with or without hospitalization over the duration of follow-up, as reported by the investigator (i.e. not validated by the Event Adjudication Committee). | Median follow-up of 4.5 years | 
| First Hospitalisation for Heart Failure (HF) | The considered event is the first overnight hospital stay for HF over the duration of the follow-up, after validation by the EAC. | Median follow-up of 4.5 years | 
| First Hospitalisation for Other Cardiovascular (CV) Cause | The considered event is the overnight hospital stay for any CV cause other than Heart Failure over the duration of follow-up, as reported by the investigator (i.e. not validated by the Event Adjudication Committee). | Median follow-up of 4.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial fibrillation, Cardiovascular disease, angiotensin II blocker