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

NCT00249873 | Completed Phase 3 Results DMC

• 1 other identifier: EFC4912 A
• Study Type: interventional
• Target: 7,554
• Locations: 29 countries
• Sites: 29

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.

Conditions

Atrial Fibrillation; Vascular Risk

Keywords

Atrial fibrillation; Anticoagulant therapy; Thromboembolic prevention

Outcome Measures

Primary Outcomes (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

  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.

  expected median follow-up of approximately 3 years

Secondary Outcomes (3)

• Occurrence of Stroke

  expected median follow-up of approximately 3 years

• Death From Any Cause (Cardiovascular and Noncardiovascular)

  expected median follow-up of approximately 3 years

• Adjudicated Major Bleedings

  expected median follow-up of approximately 3 years

Study Arms (2)

Clopidogrel + ASA

EXPERIMENTAL

Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)

Drug: clopidogrel (SR25990C)

Placebo + ASA

PLACEBO COMPARATOR

Matching placebo of clopidogrel 75 mg od plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)

Drug: placebo

Interventions

clopidogrel (SR25990C) DRUG

oral administration (tablets)

Also known as: Plavix®

Clopidogrel + ASA

placebo DRUG

oral administration (tablets)

Placebo + ASA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Sanofi: lead
• Bristol-Myers Squibb: collaborator

Study Sites (30)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, 08807, United States

Location

Sanofi-Aventis Administrative Office

Buenos Aires, Argentina

Location

Sanofi-Aventis Administrative Office

Macquarie Park, Australia

Location

Sanofi-Aventis

Vienna, Austria

Location

Sanofi-aventis Administrative Office

Diegem, Belgium

Location

Sanofi-Aventis Administrative Office

São Paulo, Brazil

Location

Sanofi-Aventis Administrative Office

Laval, Canada

Location

Sanofi-Aventis Administrative Office

Santiago, Chile

Location

Sanofi-Aventis Administrative Office

Prague, Czechia

Location

Sanofi-Aventis Administrative Office

Hørsholm, Denmark

Location

Sanofi-Aventis Administrative Office

Helsinki, Finland

Location

Sanofi-Aventis Administrative Office

Paris, France

Location

Sanofi-Aventis Administrative Office

Berlin, Germany

Location

Sanofi-Aventis Administrative Office

Athens, Greece

Location

Sanofi-Aventis Administrative Office

Causeway Bay, Hong Kong

Location

Sanofi-Aventis Administrative Office

Budapest, Hungary

Location

Sanofi-Aventis Administrative Office

Milan, Italy

Location

Sanofi-Aventis Administrative Office

Kuala Lumpur, Malaysia

Location

Sanofi-Aventis Administrative Office

México, Mexico

Location

Sanofi-Aventis Administrative Office

Gouda, Netherlands

Location

Sanofi-Aventis Administrative Office

Lysaker, Norway

Location

Sanofi-Aventis Administrative Office

Warsaw, Poland

Location

Sanofi-Aventis Administrative Office

Porto Salvo, Portugal

Location

Sanofi-Aventis Administrative Office

Singapore, Singapore

Location

Sanofi-Aventis Administrative Office

Midrand, South Africa

Location

Sanofi-Aventis Administrative Office

Barcelona, Spain

Location

Sanofi-Aventis Administrative Office

Bromma, Sweden

Location

Sanofi-Aventis Administrative Office

Geneva, Switzerland

Location

Sanofi-Aventis Administrative Office

Taipei, Taiwan

Location

Sanofi-Aventis Administrative Office

Guildford Surrey, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 19336502 RESULT

• 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.

  PMID: 20979470 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Clopidogrel

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: International Clinical Development, Clinical Study Director
• Organization: sanofi-aventis

GV-Contact-us@sanofi-aventis.com

Study Officials

• Philippe YUSUF, Prof.

  Hamilton Health Sciences Corporation

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2005
• First Posted: November 7, 2005
• Study Start: June 1, 2003
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: June 15, 2015
• Results First Posted: March 26, 2010

Record last verified: 2015-05

Locations

AU (1); FR (1); NO (1); CL (1); PT (1); CZ (1); DK (1); CA (1); GB (1); CH (1); BR (1); HU (1); TW (1); NL (1); IT (1); HK (1); DE (1); FI (1); MY (1); GR (1); ZA (1); BE (1); SE (1); AR (1); SG (1); ES (1); US (1); PL (1); ME (1)