Clinical trial NCT00249873: Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE A)
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
Vascular Risk
Keywords: Atrial fibrillation
Anticoagulant therapy
Thromboembolic prevention
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2005-11-07
Enrollment: 7554
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 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.


Eligibility 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;

Primary outcomes:
measure: 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
timeFrame: expected median follow-up of approximately 3 years
Secondary outcomes:
measure: Occurrence of Stroke
timeFrame: expected median follow-up of approximately 3 years
measure: Death From Any Cause (Cardiovascular and Noncardiovascular)
timeFrame: expected median follow-up of approximately 3 years
measure: Adjudicated Major Bleedings
timeFrame: expected median follow-up of approximately 3 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
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: Philippe YUSUF, Prof.
role: STUDY_CHAIR
References:
citation: 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.
citation: Pare 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.