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

June 11, 2024 updated by: University of Oxford

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 was a further period of at least 2 years during which participants were followed-up by telephone, off treatment.

All participants stopped study treatment prior to February 2017 (results for the main-trial have been reported) and direct participant follow-up was completed in April 2019.

In the UK we will continue to collect information on health outcomes via central data registries and NHS sources for many years.

Study Type

Interventional

Enrollment (Actual)

30449

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 7LF
        • CTSU, University of Oxford

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anacetrapib
Drug: Anacetrapib
tablet, 100mg daily
Placebo Comparator: Placebo anacetrapib
Drug: Placebo anacetrapib
tablet, 1 tablet daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Randomized treatment phase during median follow-up period of 4.1years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Randomized treatment phase during median follow-up period of 4.1years
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.
Randomized treatment phase during median follow-up period of 4.1years
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
Randomized treatment phase during median follow-up period of 4.1years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Louise Bowman, University of Oxford
  • Principal Investigator: Martin Landray, University of Oxford

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2011

Primary Completion (Actual)

January 31, 2017

Study Completion (Estimated)

January 31, 2037

Study Registration Dates

First Submitted

November 24, 2010

First Submitted That Met QC Criteria

December 1, 2010

First Posted (Estimated)

December 3, 2010

Study Record Updates

Last Update Posted (Actual)

June 25, 2024

Last Update Submitted That Met QC Criteria

June 11, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTSUREVEAL1
  • 48678192 (Registry Identifier: ISRCTN)
  • 2010-023467-18 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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/data-access.

IPD Sharing Access Criteria

See URL

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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