Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE I) - Full Text View

Sponsor:	Sanofi-Aventis
Collaborator:	Bristol-Myers Squibb
Information provided by:	Sanofi-Aventis
ClinicalTrials.gov Identifier:	NCT00249795

Purpose

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	Intervention	Phase
Atrial Fibrillation Cardiovascular Disease	Drug: Irbesartan Drug: placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, 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

Resource links provided by NLM:

Genetics Home Reference related topics: Brugada syndrome familial atrial fibrillation short QT syndrome

MedlinePlus related topics: Atrial Fibrillation Heart Attack Heart Failure

Drug Information available for: Clopidogrel Clopidogrel Bisulfate Irbesartan

U.S. FDA Resources

Further study details as provided by Sanofi-Aventis:

Primary Outcome 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 ] [ Designated as safety issue: No ]
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).
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 ] [ Designated as safety issue: No ]
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:

First Occurrence of Stroke [ Time Frame: Median follow-up of 4.5 years ] [ Designated as safety issue: No ]
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.
Death From Any Cause [ Time Frame: Median follow-up of 4.5 years ] [ Designated as safety issue: No ]
The considered event is the death over the duration of the follow-up whatever the cause, cardiovascular or non-cardiovascular.
First Occurrence of Any Heart Failure (HF) Episode [ Time Frame: Median follow-up of 4.5 years ] [ Designated as safety issue: No ]
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).
First Hospitalisation for Heart Failure (HF) [ Time Frame: Median follow-up of 4.5 years ] [ Designated as safety issue: No ]
The considered event is the first overnight hospital stay for HF over the duration of the follow-up, after validation by the EAC.
First Hospitalisation for Other Cardiovascular (CV) Cause [ Time Frame: Median follow-up of 4.5 years ] [ Designated as safety issue: No ]
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).

Enrollment:	9016
Study Start Date:	June 2003
Study Completion Date:	August 2009
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00249795

Show 30 Study Locations

Sponsors and Collaborators

Sanofi-Aventis

Bristol-Myers Squibb

Investigators

Study Chair:

Salim YUSUF, Prof.

Hamilton Health Sciences Corporation

More Information

No publications provided by Sanofi-Aventis

Additional 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.

Responsible Party:	ICD Study Director, Sanofi-aventis
ClinicalTrials.gov Identifier:	NCT00249795 History of Changes
Other Study ID Numbers:	EFC4912 I, Clopidogrel (SR25990)
Study First Received:	November 4, 2005
Results First Received:	August 24, 2010
Last Updated:	September 29, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Sanofi-Aventis:

Atrial fibrillation
Cardiovascular disease
angiotensin II blocker

Additional relevant MeSH terms:

Atrial Fibrillation
Cardiovascular Diseases
Arrhythmias, Cardiac
Heart Diseases
Pathologic Processes
Clopidogrel
Irbesartan
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Cardiovascular Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on February 09, 2012