Atrial FibrillationPhase 3ACTIVE INCT00249795
Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE I)
A Phase 3 study testing Irbesartan in people with Atrial Fibrillation and Cardiovascular Disease, run by Sanofi at 30 sites in 30 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Cardiovascular Disease
- What is being tested?
- Irbesartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9,016 participants
- Where
- 30 sitesin 30 countries
- Study dates
- Jun 2003to Aug 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
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
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 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.
Read the 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.
- Conditions
- Atrial Fibrillation, Cardiovascular Disease
- Being tested
- Irbesartan, placebo
- Keywords
- Atrial fibrillation, Cardiovascular disease, angiotensin II blocker
- Medical subject headings
- Atrial Fibrillation, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IrbesartanDrug
Also called Aprovel®
oral administration (tablets) once daily
placeboDrug
oral administration (tablets) once daily
| Study group | Role | What they receive |
|---|---|---|
| Irbesartan | Experimental | 150 mg for 2 weeks, then up-titrated to 300 mg up to final follow-up visit Receives: Drug: Irbesartan |
| Placebo | Placebo comparator | Matching placebo up to final follow-up visit 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 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).
Measured: Median follow-up of 4.5 years
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.
Measured: Median follow-up of 4.5 years
Secondary outcomes (5)
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.
Measured: Median follow-up of 4.5 years
Death From Any Cause
The considered event is the death over the duration of the follow-up whatever the cause, cardiovascular or non-cardiovascular.
Measured: Median follow-up of 4.5 years
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).
Measured: Median follow-up of 4.5 years
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.
Measured: Median follow-up of 4.5 years
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).
Measured: Median follow-up of 4.5 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 completionAug 2009
- Study completionAug 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 (1)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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 9,016 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Investigators
- Salim YUSUF, Prof., Study chair, Hamilton Health Sciences Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00249795
- Sponsor's protocol ID
- EFC4912 I
- Other IDs
- Clopidogrel (SR25990)
- Acronym
- ACTIVE I
- Status last verified
- Sep 2010
- First submitted
- 4 Nov 2005
- Last updated
- 15 Oct 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 21388310
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2010. 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
- NCT00249795
- Acronym / sponsor ID
- ACTIVE I / EFC4912 I
- Conditions
- Atrial Fibrillation, Cardiovascular Disease
- Keywords
- Atrial fibrillation, Cardiovascular disease, angiotensin II blocker
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9,016 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- Jun 2003
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 7 Nov 2005 (estimated)
- Results
- Posted 15 Oct 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 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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Irbesartan | Experimental | Drug: Irbesartan150 mg for 2 weeks, then up-titrated to 300 mg up to final follow-up visit |
| Placebo | Placebo comparator | Drug: placeboMatching placebo up to final follow-up visit |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (15 listed)
- 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
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 |
|---|---|---|
| IrbesartanAlso: Aprovel®oral administration (tablets) once daily | Drug | Irbesartan |
| placebooral administration (tablets) once daily | Drug | Placebo |
Primary outcome
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.
5 secondary outcomes
First Occurrence of Stroke
Time frame: Median follow-up of 4.5 years
Death From Any Cause
Time frame: Median follow-up of 4.5 years
First Occurrence of Any Heart Failure (HF) Episode
Time frame: Median follow-up of 4.5 years
First Hospitalisation for Heart Failure (HF)
Time frame: Median follow-up of 4.5 years
First Hospitalisation for Other Cardiovascular (CV) Cause
Time frame: Median follow-up of 4.5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21388310ACTIVE 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.
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Atrial Fibrillation (AF)
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.
Salim 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 Irbesartan in people with Atrial Fibrillation and Cardiovascular Disease, 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 5 inclusion and 15 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 Oct 2010. 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 15 Oct 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 Myocardial Infarction, Stroke or Vascular Death as Per Adjudication (time frame: Median follow-up of 4.5 years). The study lists 2 primary outcomes in all. 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 NCT00249795, which also lists 1 linked publication.
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 Oct 2010.