Clinical trial NCT00249795: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atrial Fibrillation
Cardiovascular Disease
Keywords: Atrial fibrillation
Cardiovascular disease
angiotensin II blocker
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2005-11-07
Enrollment: 9016
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: First Occurence of Any Component of the Composite of Myocardial Infarction, Stroke or Vascular Death as Per Adjudication
timeFrame: Median follow-up of 4.5 years
measure: First Occurence of Any Component of the Composite of Myocardial Infarction, Stroke, Vascular Death or Hospitalization for Heart Failure as Per Adjudication
timeFrame: Median follow-up of 4.5 years
Secondary outcomes:
measure: First Occurrence of Stroke
timeFrame: Median follow-up of 4.5 years
measure: Death From Any Cause
timeFrame: Median follow-up of 4.5 years
measure: First Occurrence of Any Heart Failure (HF) Episode
timeFrame: Median follow-up of 4.5 years
measure: First Hospitalisation for Heart Failure (HF)
timeFrame: Median follow-up of 4.5 years
measure: First Hospitalisation for Other Cardiovascular (CV) Cause
timeFrame: Median follow-up of 4.5 years
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Buenos Aires
country: Argentina
facility: Sanofi-Aventis Administrative Office
city: Macquarie Park
country: Australia
facility: Sanofi-Aventis Administrative Office
city: Wien
country: Austria
facility: Sanofi-Aventis Administrative Office
city: Diegem
country: Belgium
facility: Sanofi-Aventis Administrative Office
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Santiago
country: Chile
facility: Sanofi-Aventis Administrative Office
city: Praha
country: Czech Republic
facility: Sanofi-Aventis Administrative Office
city: Horsholm
country: Denmark
facility: Sanofi-Aventis Administrative Office
city: Helsinki
country: Finland
facility: Sanofi-Aventis Administrative Office
city: Paris
country: France
facility: Sanofi-Aventis Administrative Office
city: Berlin
country: Germany
facility: Sanofi-Aventis Administrative Office
city: Athens
country: Greece
facility: Sanofi-Aventis Administrative Office
city: Causeway Bay
country: Hong Kong
facility: Sanofi-Aventis Administrative Office
city: Budapest
country: Hungary
facility: Sanofi-Aventis Administrative Office
city: Milano
country: Italy
facility: Sanofi-Aventis Administrative Office
city: Kuala Lumpur
country: Malaysia
facility: Sanofi-Aventis Administrative Office
city: Mexico
country: Mexico
facility: Sanofi-Aventis Administrative Office
city: Gouda
country: Netherlands
facility: Sanofi-Aventis Administrative Office
city: Lysaker
country: Norway
facility: Sanofi-Aventis Administrative Office
city: Warszawa
country: Poland
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Singapore
country: Singapore
facility: Sanofi-Aventis Administrative Office
city: Midrand
country: South Africa
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Bromma
country: Sweden
facility: Sanofi-Aventis Administrative Office
city: Geneva
country: Switzerland
facility: Sanofi-Aventis Administrative Office
city: Taipei
country: Taiwan
facility: Sanofi-Aventis Administrative Office
city: Guildford Surrey
country: United Kingdom
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Hamilton Health Sciences Corporation
name: Salim YUSUF, Prof.
role: STUDY_CHAIR
References:
citation: ACTIVE I Investigators; Yusuf S, Healey JS, Pogue J, Chrolavicius S, Flather M, Hart RG, Hohnloser SH, Joyner CD, Pfeffer MA, Connolly SJ. Irbesartan in patients with atrial fibrillation. N Engl J Med. 2011 Mar 10;364(10):928-38. doi: 10.1056/NEJMoa1008816.