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

• ClinicalTrials.gov Identifier: NCT00249795
• Recruitment Status: Completed
• First Posted: November 7, 2005
• Results First Posted: October 15, 2010
• Last Update Posted: October 15, 2010
• Sponsor: Sanofi
• Collaborator: Bristol-Myers Squibb
• Information provided by: Sanofi

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation; Cardiovascular Disease	Drug: Irbesartan; Drug: placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9016 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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 Start Date: June 2003
• Actual Primary Completion Date: August 2009
• Actual Study Completion Date: August 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Irbesartan; 150 mg for 2 weeks, then up-titrated to 300 mg up to final follow-up visit	Drug: Irbesartan; oral administration (tablets) once daily; Other Name: Aprovel®
Placebo Comparator: Placebo; Matching placebo up to final follow-up visit	Drug: placebo; oral administration (tablets) once daily

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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).
2. 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 ]
   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.

Secondary Outcome Measures :

1. First Occurrence of Stroke [ Time Frame: Median follow-up of 4.5 years ]
   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.
2. Death From Any Cause [ Time Frame: Median follow-up of 4.5 years ]
   The considered event is the death over the duration of the follow-up whatever the cause, cardiovascular or non-cardiovascular.
3. First Occurrence of Any Heart Failure (HF) Episode [ Time Frame: Median follow-up of 4.5 years ]
   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).
4. First Hospitalisation for Heart Failure (HF) [ Time Frame: Median follow-up of 4.5 years ]
   The considered event is the first overnight hospital stay for HF over the duration of the follow-up, after validation by the EAC.
5. First Hospitalisation for Other Cardiovascular (CV) Cause [ Time Frame: Median follow-up of 4.5 years ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New Jersey

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States, 08807

Argentina

Sanofi-Aventis Administrative Office

Buenos Aires, Argentina

Australia

Sanofi-Aventis Administrative Office

Macquarie Park, Australia

Austria

Sanofi-Aventis Administrative Office

Wien, Austria

Belgium

Sanofi-Aventis Administrative Office

Diegem, Belgium

Brazil

Sanofi-Aventis Administrative Office

Sao Paulo, Brazil

Canada

Sanofi-Aventis Administrative Office

Laval, Canada

Chile

Sanofi-Aventis Administrative Office

Santiago, Chile

Czech Republic

Sanofi-Aventis Administrative Office

Praha, Czech Republic

Denmark

Sanofi-Aventis Administrative Office

Horsholm, Denmark

Finland

Sanofi-Aventis Administrative Office

Helsinki, Finland

France

Sanofi-Aventis Administrative Office

Paris, France

Germany

Sanofi-Aventis Administrative Office

Berlin, Germany

Greece

Sanofi-Aventis Administrative Office

Athens, Greece

Hong Kong

Sanofi-Aventis Administrative Office

Causeway Bay, Hong Kong

Hungary

Sanofi-Aventis Administrative Office

Budapest, Hungary

Italy

Sanofi-Aventis Administrative Office

Milano, Italy

Malaysia

Sanofi-Aventis Administrative Office

Kuala Lumpur, Malaysia

Mexico

Sanofi-Aventis Administrative Office

Mexico, Mexico

Netherlands

Sanofi-Aventis Administrative Office

Gouda, Netherlands

Norway

Sanofi-Aventis Administrative Office

Lysaker, Norway

Poland

Sanofi-Aventis Administrative Office

Warszawa, Poland

Portugal

Sanofi-Aventis Administrative Office

Porto Salvo, Portugal

Singapore

Sanofi-Aventis Administrative Office

Singapore, Singapore

South Africa

Sanofi-Aventis Administrative Office

Midrand, South Africa

Spain

Sanofi-Aventis Administrative Office

Barcelona, Spain

Sweden

Sanofi-Aventis Administrative Office

Bromma, Sweden

Switzerland

Sanofi-Aventis Administrative Office

Geneva, Switzerland

Taiwan

Sanofi-Aventis Administrative Office

Taipei, Taiwan

United Kingdom

Sanofi-Aventis Administrative Office

Guildford Surrey, United Kingdom

Sponsors and Collaborators

Sanofi

Bristol-Myers Squibb

Investigators

• Study Chair: Salim YUSUF, Prof.; Hamilton Health Sciences Corporation

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: ICD Study Director, Sanofi-aventis
• ClinicalTrials.gov Identifier: NCT00249795
• Other Study ID Numbers: EFC4912 I; Clopidogrel (SR25990)
• First Posted: November 7, 2005
• Results First Posted: October 15, 2010
• Last Update Posted: October 15, 2010
• Last Verified: September 2010

Keywords provided by Sanofi:

Atrial fibrillation; Cardiovascular disease; angiotensin II blocker

Additional relevant MeSH terms:

Atrial Fibrillation; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Irbesartan; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action