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

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ClinicalTrials.gov Identifier: NCT00249795
Recruitment Status : Completed
First Posted : November 7, 2005
Results First Posted : October 15, 2010
Last Update Posted : October 15, 2010
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
Sanofi

Tracking Information
First Submitted Date  ICMJE November 4, 2005
First Posted Date  ICMJE November 7, 2005
Results First Submitted Date  ICMJE August 24, 2010
Results First Posted Date  ICMJE October 15, 2010
Last Update Posted Date October 15, 2010
Study Start Date  ICMJE June 2003
Actual Primary Completion Date August 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 29, 2010)
  • First Occurence of Any Component of the Composite of Myocardial Infarction, Stroke or Vascular Death as Per Adjudication [ Time Frame: Median follow-up of 4.5 years ]
    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).
  • First Occurence of Any Component of the Composite of Myocardial Infarction, Stroke, Vascular Death or Hospitalization for Heart Failure as Per Adjudication [ Time Frame: Median follow-up of 4.5 years ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 4, 2005)
  • The primary outcome of the study is: irbesartan, compared to placebo will reduce the risk of the first composite outcome of stroke, myocardial infarction or vascular death.
  • The second primary outcome of the study is irbesartan, compared to placebo will reduce the risk of the second composite outcome of stroke, myocardial infarction, vascular death or hospitalization for heart failure.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 29, 2010)
  • First Occurrence of Stroke [ Time Frame: Median follow-up of 4.5 years ]
    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.
  • Death From Any Cause [ Time Frame: Median follow-up of 4.5 years ]
    The considered event is the death over the duration of the follow-up whatever the cause, cardiovascular or non-cardiovascular.
  • First Occurrence of Any Heart Failure (HF) Episode [ Time Frame: Median follow-up of 4.5 years ]
    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).
  • First Hospitalisation for Heart Failure (HF) [ Time Frame: Median follow-up of 4.5 years ]
    The considered event is the first overnight hospital stay for HF over the duration of the follow-up, after validation by the EAC.
  • First Hospitalisation for Other Cardiovascular (CV) Cause [ Time Frame: Median follow-up of 4.5 years ]
    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).
Original Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2005)
The secondary outcomes are total mortality, stroke, hospitalization for heart failure and other heart failure episodes defined as evidence of symptoms or signs of heart failure (with or without hospitalization).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE I)
Official Title  ICMJE 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
Brief 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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Atrial Fibrillation
  • Cardiovascular Disease
Intervention  ICMJE
  • Drug: Irbesartan
    oral administration (tablets) once daily
    Other Name: Aprovel®
  • Drug: placebo
    oral administration (tablets) once daily
Study Arms  ICMJE
  • Experimental: Irbesartan
    150 mg for 2 weeks, then up-titrated to 300 mg up to final follow-up visit
    Intervention: Drug: Irbesartan
  • Placebo Comparator: Placebo
    Matching placebo up to final follow-up visit
    Intervention: Drug: placebo
Publications * ACTIVE I Investigators, Yusuf S, Healey JS, Pogue J, Chrolavicius S, Flather M, Hart RG, Hohnloser SH, Joyner CD, Pfeffer MA, Connolly SJ. Irbesartan in patients with atrial fibrillation. N Engl J Med. 2011 Mar 10;364(10):928-38. doi: 10.1056/NEJMoa1008816.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 29, 2010)
9016
Original Enrollment  ICMJE
 (submitted: November 4, 2005)
9000
Actual Study Completion Date  ICMJE August 2009
Actual Primary Completion Date August 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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,   United States
Removed Location Countries Israel,   Russian Federation,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT00249795
Other Study ID Numbers  ICMJE EFC4912 I
Clopidogrel (SR25990)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ICD Study Director, Sanofi-aventis
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Study Chair: Salim YUSUF, Prof. Hamilton Health Sciences Corporation
PRS Account Sanofi
Verification Date September 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP