Atrial FibrillationPhase 3NCT00249873
Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE A)
A Phase 3 study testing clopidogrel (SR25990C) in people with Atrial Fibrillation and Vascular Risk, run by Sanofi at 30 sites in 30 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Vascular Risk
- What is being tested?
- clopidogrel (SR25990C)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7,554 participants
- Where
- 30 sitesin 30 countries
- Study dates
- Jun 2003to Mar 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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;
Trial locations and contacts
30 sites in 30 countries.
30 sites in 30 countries
United States1 site
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, 08807
United Kingdom1 site
Sanofi-Aventis Administrative Office
Guildford Surrey
About this study
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
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
- Being tested
- clopidogrel (SR25990C), placebo
- Keywords
- Atrial fibrillation, Anticoagulant therapy, Thromboembolic prevention
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clopidogrel (SR25990C)Drug
Also called Plavix®
oral administration (tablets)
placeboDrug
oral administration (tablets)
| Study group | Role | What they receive |
|---|---|---|
| Clopidogrel + ASA | Experimental | Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion) Receives: 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) Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: expected median follow-up of approximately 3 years
Secondary outcomes (3)
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.
Measured: expected median follow-up of approximately 3 years
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.
Measured: expected median follow-up of approximately 3 years
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).
Measured: expected median follow-up of approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2005 (estimated)
- Study startJun 2003
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 7,554 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Philippe YUSUF, Prof., Study chair, Hamilton Health Sciences Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00249873
- Sponsor's protocol ID
- EFC4912 A
- Status last verified
- May 2015
- First submitted
- 4 Nov 2005
- Last updated
- 15 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 19336502Pare 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.
PubMed 20979470
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00249873
- Acronym / sponsor ID
- EFC4912 A
- Conditions
- Atrial Fibrillation, Vascular Risk
- Keywords
- Atrial fibrillation, Anticoagulant therapy, Thromboembolic prevention
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7,554 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- Jun 2003
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 7 Nov 2005 (estimated)
- Results
- Posted 26 Mar 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clopidogrel + ASA | Experimental | Drug: clopidogrel (SR25990C)Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion) |
| Placebo + ASA | Placebo comparator | Drug: placeboMatching placebo of clopidogrel 75 mg od plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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 :
- To have either a contraindication to use an oral anticoagulant treatment or they are unwilling to take an oral anticoagulant treatment.
Key exclusion criteria (13 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| clopidogrel (SR25990C)Also: Plavix®oral administration (tablets) | Drug | Clopidogrel + ASA |
| placebooral administration (tablets) | Drug | Placebo + ASA |
Primary outcome
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
Time frame: expected median follow-up of approximately 3 years
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.
3 secondary outcomes
Occurrence of Stroke
Time frame: expected median follow-up of approximately 3 years
Death From Any Cause (Cardiovascular and Noncardiovascular)
Time frame: expected median follow-up of approximately 3 years
Adjudicated Major Bleedings
Time frame: expected median follow-up of approximately 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19336502ACTIVE 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.
- Derived from this study: PubMed 20979470Pare 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philippe YUSUF, Prof. study chair
Hamilton Health Sciences Corporation
30 sites in 30 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing clopidogrel (SR25990C) in people with Atrial Fibrillation and Vascular Risk, run by Sanofi at 30 sites in 30 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Argentina, Australia, Austria, Belgium and 25 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: expected median follow-up of approximately 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00249873, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2015.