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

• ClinicalTrials.gov Identifier: NCT00249873
• Recruitment Status: Completed
• First Posted: November 7, 2005
• Results First Posted: March 26, 2010
• Last Update Posted: June 15, 2015
• Sponsor: Sanofi
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Atrial Fibrillation; Vascular Risk	Drug: clopidogrel (SR25990C); Drug: placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7554 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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
• Study Start Date: June 2003
• Actual Primary Completion Date: March 2009
• Actual Study Completion Date: March 2009

Arms and Interventions

Arm	Intervention/treatment
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)

Outcome Measures

Primary Outcome Measures :

1. 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 ]

   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 :

1. Occurrence of Stroke [ Time Frame: expected median follow-up of approximately 3 years ]
   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.
2. Death From Any Cause (Cardiovascular and Noncardiovascular) [ Time Frame: expected median follow-up of approximately 3 years ]
   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.
3. Adjudicated Major Bleedings [ Time Frame: expected median follow-up of approximately 3 years ]
   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).

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:

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

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

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: Philippe YUSUF, Prof.; Hamilton Health Sciences Corporation

More Information

Publications of Results:

ACTIVE Investigators, Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M, Chrolavicius S, Yusuf S. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med. 2009 May 14;360(20):2066-78. doi: 10.1056/NEJMoa0901301. Epub 2009 Mar 31.

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

Paré G, Mehta SR, Yusuf S, Anand SS, Connolly SJ, Hirsh J, Simonsen K, Bhatt DL, Fox KA, Eikelboom JW. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med. 2010 Oct 28;363(18):1704-14. doi: 10.1056/NEJMoa1008410. Epub 2010 Aug 29.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT00249873
• Other Study ID Numbers: EFC4912 A
• First Posted: November 7, 2005
• Results First Posted: March 26, 2010
• Last Update Posted: June 15, 2015
• Last Verified: May 2015

Keywords provided by Sanofi:

Atrial fibrillation; Anticoagulant therapy; Thromboembolic prevention

Additional relevant MeSH terms:

Atrial Fibrillation; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Clopidogrel; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs