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

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00249873
First received: November 4, 2005
Last updated: March 31, 2010
Last verified: March 2010
  Purpose

The purpose of this study is to determine if the combination of clopidogrel 75mg once daily (od) plus aspirin 100mg daily (recommended dose) is better than aspirin alone (100mg daily recommended dose) for preventing vascular events such as stroke and heart attack during approximately three years of follow-up in patients with atrial fibrillation associated with at least one major risk factor of vascular event such as elderly, blood pressure increase, history of stroke or transient ischemic attack or left ventricular dysfunction etc. The study will also accept patients with atrial fibrillation and unwilling to take oral anticoagulant therapy.


Condition Intervention Phase
Atrial Fibrillation
Vascular Risk
Drug: clopidogrel (SR25990C)
Drug: placebo
Phase 3

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


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • First Occurence of Any Component of the Composite of Stroke, Non-Central Nervous System (Non-CNS) Systemic Embolism, Myocardial Infarction or Vascular Death as Per Adjudication [ Time Frame: expected median follow-up of approximately 3 years ] [ Designated as safety issue: No ]

    The primary event is the first occurence of any adjudicated component of the following cluster over the duration of follow-up :

    • stroke (nonfatal or fatal)
    • myocardial infarction (nonfatal or fatal)
    • non-CNS systemic embolism
    • vascular death

    The primary efficacy analysis is performed on the time from randomization to this primary event. Numbers of patients with the composite event over the duration of the follow-up are presented by arm group.



Secondary Outcome Measures:
  • Occurrence of Stroke [ Time Frame: expected median follow-up of approximately 3 years ] [ Designated as safety issue: No ]
    The event is the occurence of stroke (nonfatal or fatal, ischemic, hemorrhagic or of uncertain type) after validation of the Event Adjudication Committee . The analysis is performed on the time from randomization to the occurrence of this event. Numbers of patients with the event over the duration of the follow-up are presented by arm group.

  • Death From Any Cause (Cardiovascular and Noncardiovascular) [ Time Frame: expected median follow-up of approximately 3 years ] [ Designated as safety issue: No ]
    The considered event is death from any cause. The analysis is performed on the time from randomization to this event. Numbers of patients with the event over the duration of the follow-up are presented by arm group.

  • Adjudicated Major Bleedings [ Time Frame: expected median follow-up of approximately 3 years ] [ Designated as safety issue: Yes ]
    The number of participants with at least one major bleeding, validated by the Event Adjudication Committee are counted over the duration of the follow-up (including after permanent discontinuation of the study drug).


Enrollment: 7554
Study Start Date: June 2003
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clopidogrel + ASA
Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)
Drug: clopidogrel (SR25990C)
oral administration (tablets)
Other Name: Plavix®
Placebo Comparator: Placebo + ASA
Matching placebo of clopidogrel 75 mg od plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)
Drug: placebo
oral administration (tablets)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be eligible for ACTIVE A patients must have in same time the three following conditions :

  • Evidence of atrial fibrillation either on one current Electrocardiogram (ECG) or two ECGs recorded at two weeks a part during 6 months prior to study enrollment.
  • Evidence of high risk of vascular events : at least one of the following risk criteria must be present :

    • are 75 years greater;
    • on treatment for systemic hypertension;
    • prior stroke, Transient Ischemic Attack (TIA) or non-Central Nervous System (non-CNS) systemic embolus;
    • left ventricular dysfunction with left ventricular ejection fraction (EF) estimated by echocardiogram or angiogram (radionuclide or contrast) to be < 45%;
    • peripheral vascular disease (previous peripheral artery revascularization, limb and foot amputation, or the combination of current intermittent claudication and ankle arm systolic blood pressure ratio < 0.9);
    • age 55 to 74 years and either; f1) diabetes mellitus requiring drug therapy, or f2) documented previous myocardial infarction or documented coronary artery disease.
  • To have either a contraindication to use an oral anticoagulant treatment or they are unwilling to take an oral anticoagulant treatment.

Exclusion Criteria:

Patients will be excluded from ACTIVE 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 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;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00249873

  Show 30 Study Locations
Sponsors and Collaborators
Sanofi
Bristol-Myers Squibb
Investigators
Study Chair: Philippe YUSUF, Prof. Hamilton Health Sciences Corporation
  More Information

No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: International Clinical Development Study Director, Sanofi-aventis
ClinicalTrials.gov Identifier: NCT00249873     History of Changes
Other Study ID Numbers: EFC4912 A
Study First Received: November 4, 2005
Results First Received: March 8, 2010
Last Updated: March 31, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Atrial fibrillation
Anticoagulant therapy
Thromboembolic prevention

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Clopidogrel
Ticlopidine
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014