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REVEAL: Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL)

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ClinicalTrials.gov Identifier: NCT01252953
Recruitment Status : Active, not recruiting
First Posted : December 3, 2010
Results First Posted : May 4, 2018
Last Update Posted : March 18, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Oxford

Tracking Information
First Submitted Date  ICMJE November 24, 2010
First Posted Date  ICMJE December 3, 2010
Results First Submitted Date February 1, 2018
Results First Posted Date May 4, 2018
Last Update Posted Date March 18, 2019
Study Start Date  ICMJE June 2011
Actual Primary Completion Date January 31, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 6, 2018)
Number of Participants With Major Coronary Event [ Time Frame: Randomized treatment phase during median follow-up period of 4.1years ]
Primary assessment involves an intention-to-treat comparison among all randomized participants of the effects of allocation to anacetrapib versus placebo on major coronary events (defined as the occurrence of coronary death, myocardial infarction or coronary revascularization procedure) during the scheduled treatment period. Data reported is for the first major coronary event.
Original Primary Outcome Measures  ICMJE
 (submitted: December 1, 2010)
Major coronary events (defined as coronary death, myocardial infarction or coronary revascularization procedure) [ Time Frame: Median follow-up of 4 years ]
Primary assessment will involve an intention-to-treat comparison among all randomized participants of the effects of allocation to anacetrapib versus placebo on major coronary events (defined as the occurrence of coronary death, myocardial infarction or coronary revascularization procedure) during the scheduled treatment period.
Change History Complete list of historical versions of study NCT01252953 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 6, 2018)
  • Number of Participants With Major Atherosclerotic Event [ Time Frame: Randomized treatment phase during median follow-up period of 4.1years ]
    Major atherosclerotic events (defined as coronary death, myocardial infarction or presumed ischaemic stroke; the key secondary outcome). Secondary assessments involve intention-to-treat comparisons among all randomized participants of the effects of allocation to anacetrapib versus placebo during the scheduled treatment period.
  • Number of Participants With Presumed Ischaemic Stroke [ Time Frame: Randomized treatment phase during median follow-up period of 4.1years ]
    Presumed ischaemic stroke (i.e. not known to be haemorrhagic). Secondary assessments involve intention-to-treat comparisons among all randomized participants of the effects of allocation to anacetrapib versus placebo during the scheduled treatment period.
  • Number of Participants With Major Vascular Event [ Time Frame: Randomized treatment phase during median follow-up period of 4.1years ]
    Major vascular events (defined as coronary death, myocardial infarction, coronary revascularization or presumed ischaemic stroke). Secondary assessments involve intention-to-treat comparisons among all randomized participants of the effects of allocation to anacetrapib versus placebo during the scheduled treatment period
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE REVEAL: Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification
Official Title  ICMJE REVEAL: Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification. A Large-scale, Randomized Placebo-controlled Trial of the Clinical Effects of Anacetrapib Among People With Established Vascular Disease
Brief Summary The Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) trial aims to determine whether lipid modification with anacetrapib 100mg daily reduces the risk of coronary death, myocardial infarction (MI) or coronary revascularization (collectively known as major coronary events) in patients with circulatory problems who have their Low-density Lipoprotein (LDL) cholesterol level treated with a statin.
Detailed Description

Sub-study: Does anacetrapib as a CETP inhibitor lead to mobilization of stem cells and enhance myocardial function via neoangiogenesis and tissue regeneration?

Following the main on-treatment part of the study, there will be a further period of at least 2 years during which participants will be followed-up by telephone, off treatment.

Study Type  ICMJE Interventional
Study Phase Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Atherosclerotic Cardiovascular Disease
Intervention  ICMJE
  • Drug: Anacetrapib
    tablet, 100mg daily
  • Drug: Placebo anacetrapib
    tablet, 1 tablet daily
Study Arms
  • Experimental: Anacetrapib
    Intervention: Drug: Anacetrapib
  • Placebo Comparator: Placebo anacetrapib
    Intervention: Drug: Placebo anacetrapib
Publications *

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 6, 2018)
30449
Original Estimated Enrollment  ICMJE
 (submitted: December 1, 2010)
30000
Estimated Study Completion Date April 2019
Actual Primary Completion Date January 31, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must be aged at least 50 at the time of initial invitation, and at least one of the following inclusion criteria must be satisfied:

    • History of MI; or
    • Cerebrovascular atherosclerotic disease (i.e. history of presumed ischaemic stroke or carotid revascularization); or
    • Peripheral arterial disease (i.e. history of non-coronary revascularization, including aortic aneurysm repair or graft); or
    • Diabetes mellitus with other evidence of symptomatic coronary heart disease (i.e. treatment or hospitalization for angina, or a history of coronary revascularization or acute coronary syndrome).

Exclusion Criteria:

  • None of the following must be satisfied:

    • Acute MI, acute coronary syndrome or stroke within 4 weeks prior to Screening Visit or during Run-in (but such individuals may be entered later, if appropriate);
    • Planned coronary revascularization procedure within the next 6 months (such individuals may be entered later, if appropriate);
    • Definite history of chronic liver disease, or abnormal liver function (i.e. alanine transaminase (ALT) >2x the upper limit of normal (ULN)). Note: Individuals with a history of acute hepatitis are eligible provided this ALT limit is not exceeded;
    • Severe renal insufficiency (i.e. creatinine >200 µmol/L [2.3 mg/dL], dialysis or functioning renal transplant);
    • Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or creatine kinase (CK) >3x ULN;
    • Previous significant adverse reaction to a statin or anacetrapib;
    • Current treatment with any of the following lipid-lowering treatments:

      (i) a regimen considered to produce substantially greater LDL cholesterol reduction than atorvastatin 80 mg daily for individuals in non-Asian countries or 20 mg daily for those in North East Asia; or (ii) fibric acid derivative ("fibrate", including gemfibrozil); or (iii) niacin (nicotinic acid) at doses above 100 mg daily

    • Concurrent treatment with a medication that is contraindicated with anacetrapib or atorvastatin:

      (i) any potent CYP3A4 inhibitor, such as:

      1. macrolide antibiotics (erythromycin, clarithromycin, telithromycin);
      2. systemic imidazole or triazole antifungals (e.g. itraconazole, posaconazole);
      3. protease inhibitors (e.g. atazanavir);
      4. nefazodone

        (ii) ciclosporin

        (iii) daptomycin

        (iv) systemic use of fusidic acid

        Note: Individuals who are taking such drugs temporarily may be re-screened when they discontinue them, if considered appropriate;

    • Known to be poorly compliant with clinic visits or prescribed medication;
    • Medical history that might limit the individual's ability to take trial treatments for the duration of the study (e.g. severe respiratory disease; history of cancer or evidence of spread within last 5 years, other than non-melanoma skin cancer; or recent history of alcohol or substance misuse);
    • Women of child-bearing potential (unless using adequate contraception);
    • Current participation in a clinical trial with an unlicensed drug or device.

Individuals will also be excluded at the Screening visit if it is considered unlikely that they will achieve total cholesterol <3.5 mmol/L (135 mg/dL) on the highest atorvastatin dose available in their region (atorvastatin 80 mg daily in non-Asian countries or 20 mg daily in North East Asia).

In addition, individuals will be excluded at the Randomization visit if any of the following are true:

  • Total cholesterol above 4 mmol/L [155 mg/dL]
  • Non-compliant with run-in treatment (<90% scheduled run-in medication taken)
  • Individual is no longer willing to be randomized into the 4-5 year trial
  • The individual's doctor is of the view that their patient should not be randomized.
Sex/Gender
Sexes Eligible for Study: All
Ages 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01252953
Other Study ID Numbers  ICMJE CTSUREVEAL1
48678192 ( Registry Identifier: ISRCTN )
2010-023467-18 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Yes
Plan Description: Proposals for substudies must be approved by the Steering Committee. Procedures for accessing the data for this study are available on: https://www.ndph.ox.ac.uk/about/data-access-policy.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Access Criteria: See URL.
URL: https://www.ndph.ox.ac.uk/about/data-access-policy
Responsible Party University of Oxford
Study Sponsor  ICMJE University of Oxford
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Martin Landray University of Oxford
Principal Investigator: Louise Bowman University of Oxford
PRS Account University of Oxford
Verification Date April 2018

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