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

Atrial Fibrillation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00249873
• Other study ID #: EFC4912 A
• Status: Completed
• Phase: Phase 3
• First received: November 4, 2005
• Last updated: May 20, 2015
• Start date: June 2003
• Est. completion date: March 2009

Study information

• Verified date: May 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7554
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrial Fibrillation
• Vascular Risk

Intervention

Drug:
• clopidogrel (SR25990C)
oral administration (tablets)
• placebo
oral administration (tablets)

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Administrative Office	Buenos Aires
Australia	Sanofi-Aventis Administrative Office	Macquarie Park
Austria	Sanofi-Aventis	Wien
Belgium	Sanofi-aventis Administrative Office	Diegem
Brazil	Sanofi-Aventis Administrative Office	Sao Paulo
Canada	Sanofi-Aventis Administrative Office	Laval
Chile	Sanofi-Aventis Administrative Office	Santiago
Czech Republic	Sanofi-Aventis Administrative Office	Praha
Denmark	Sanofi-Aventis Administrative Office	Horsholm
Finland	Sanofi-Aventis Administrative Office	Helsinki
France	Sanofi-Aventis Administrative Office	Paris
Germany	Sanofi-Aventis Administrative Office	Berlin
Greece	Sanofi-Aventis Administrative Office	Athens
Hong Kong	Sanofi-Aventis Administrative Office	Causeway Bay
Hungary	Sanofi-Aventis Administrative Office	Budapest
Italy	Sanofi-Aventis Administrative Office	Milano
Malaysia	Sanofi-Aventis Administrative Office	Kuala Lumpur
Mexico	Sanofi-Aventis Administrative Office	Mexico
Netherlands	Sanofi-Aventis Administrative Office	Gouda
Norway	Sanofi-Aventis Administrative Office	Lysaker
Poland	Sanofi-Aventis Administrative Office	Warszawa
Portugal	Sanofi-Aventis Administrative Office	Porto Salvo
Singapore	Sanofi-Aventis Administrative Office	Singapore
South Africa	Sanofi-Aventis Administrative Office	Midrand
Spain	Sanofi-Aventis Administrative Office	Barcelona
Sweden	Sanofi-Aventis Administrative Office	Bromma
Switzerland	Sanofi-Aventis Administrative Office	Geneva
Taiwan	Sanofi-Aventis Administrative Office	Taipei
United Kingdom	Sanofi-Aventis Administrative Office	Guildford Surrey
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Italy,  Malaysia,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Singapore,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Occurrence of Stroke	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.	expected median follow-up of approximately 3 years	No
Secondary	Death From Any Cause (Cardiovascular and Noncardiovascular)	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.	expected median follow-up of approximately 3 years	No
Secondary	Adjudicated Major Bleedings	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).	expected median follow-up of approximately 3 years	Yes