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

Atrial Fibrillation Clinical Trial

— ACTIVE I  

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: NCT00249795
• Other study ID #: EFC4912 I
• Secondary ID: Clopidogrel (SR2
• Status: Completed
• Phase: Phase 3
• First received: November 4, 2005
• Last updated: September 29, 2010
• Start date: June 2003
• Est. completion date: August 2009

Study information

• Verified date: September 2010
• 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 was to determine if Irbesartan compared to Placebo would reduce the risk of vascular events such as heart attack, stroke, non-cerebral thromboembolic event and death in patients with Atrial Fibrillation (AF) and with at least one major risk of vascular events.

Description:

ACTIVE I was one of the 3 separate but related trials of the ACTIVE program conducted in AF patients at risk of vascular events.

Patients were enrolled first into one of the 2 parallel trials of the ACTIVE program evaluating Clopidogrel:

• ACTIVE A comparing clopidogrel + acetylsalicylic acid (ASA) and ASA alone

• ACTIVE W comparing clopidogrel + ASA and oral anticoagulant (OAC).

Then those satisfying additional criteria related to blood pressure and angiotensin receptor blocking agents were re-randomized in the two ACTIVE I arms according to a separate randomization list.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9016
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Should fulfill the eligibility criteria for ACTIVE A or ACTIVE W trial and:

• have a systolic blood pressure of at least 110 mmHg

• not already receiving an angiotensin receptor blocking agent, unless they are willing and able to be changed to another antihypertensive agent

• no previous intolerance to angiotensin receptor blocking agents

• no proven indication for angiotensin receptor blocking agents, unless an Angiotensin Converting Enzyme (ACE) inhibitor can be substituted

Exclusion Criteria:

Patients will be excluded from ACTIVE study 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 acetylsalicyclic acid (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

• requirement for chronic (> 3 months) non-cyclooxygenase-2 (non-COX-2) inhibitor nonsteroidal anti-inflammatory drug (NSAID) therapy unless willing enrolled in ACTIVE A

Study Design

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• Irbesartan
oral administration (tablets) once daily
• placebo
oral administration (tablets) once daily

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Administrative Office	Buenos Aires
Australia	Sanofi-Aventis Administrative Office	Macquarie Park
Austria	Sanofi-Aventis Administrative Office	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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First Occurence of Any Component of the Composite of Myocardial Infarction, Stroke or Vascular Death as Per Adjudication	The first co-primary event is the first occurence of any component of the following cluster over the duration of follow-up: myocardial infarction (nonfatal or fatal), stroke (nonfatal or fatal) or vascular death - after validation by the Event Adjudication Committee (EAC).	Median follow-up of 4.5 years	No
Primary	First Occurence of Any Component of the Composite of Myocardial Infarction, Stroke, Vascular Death or Hospitalization for Heart Failure as Per Adjudication	The second co-primary event is the first occurence of any component of the following cluster over the duration of follow-up: myocardial infarction (nonfatal or fatal), stroke (nonfatal or fatal), vascular death or hospitalization for heart failure - after validation by the EAC.	Median follow-up of 4.5 years	No
Secondary	First Occurrence of Stroke	The considered event is the first occurrence of stroke (nonfatal or fatal, ischemic, hemorrhagic or of uncertain type) over the duration of follow-up, after validation by the EAC.	Median follow-up of 4.5 years	No
Secondary	Death From Any Cause	The considered event is the death over the duration of the follow-up whatever the cause, cardiovascular or non-cardiovascular.	Median follow-up of 4.5 years	No
Secondary	First Occurrence of Any Heart Failure (HF) Episode	The considered event is the first occurence of any HF episode defined as evidence of signs and symptoms of HF with or without hospitalization over the duration of follow-up, as reported by the investigator (i.e. not validated by the Event Adjudication Committee).	Median follow-up of 4.5 years	No
Secondary	First Hospitalisation for Heart Failure (HF)	The considered event is the first overnight hospital stay for HF over the duration of the follow-up, after validation by the EAC.	Median follow-up of 4.5 years	No
Secondary	First Hospitalisation for Other Cardiovascular (CV) Cause	The considered event is the overnight hospital stay for any CV cause other than Heart Failure over the duration of follow-up, as reported by the investigator (i.e. not validated by the Event Adjudication Committee).	Median follow-up of 4.5 years	No