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

Atherosclerotic Cardiovascular Disease Clinical Trial

— REVEAL  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01252953
• Other study ID #: CTSUREVEAL1
• Secondary ID: 486781922010-023
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 2011
• Est. completion date: January 31, 2037

Study information

• Verified date: May 2023
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30449
• Est. completion date: January 31, 2037
• Est. primary completion date: January 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerotic Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• Anacetrapib
tablet, 100mg daily
• Placebo anacetrapib
tablet, 1 tablet daily

Locations

Country	Name	City	State
United Kingdom	CTSU, University of Oxford	Oxford	Oxfordshire

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

Hopewell JC, Ibrahim M, Hill M, Shaw PM, Braunwald E, Blaustein RO, Bowman L, Landray MJ, Sabatine MS, Collins R; HPS3/TIMI55 - REVEAL Collaborative Group. Impact of ADCY9 Genotype on Response to Anacetrapib. Circulation. 2019 Jul 23;140(11):891-8. doi: 1 — View Citation

HPS3/TIMI55-REVEAL Collaborative Group; Bowman L, Hopewell JC, Chen F, Wallendszus K, Stevens W, Collins R, Wiviott SD, Cannon CP, Braunwald E, Sammons E, Landray MJ. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease. N Engl J Med. — View Citation

HPS3/TIMI55-REVEAL Collaborative Group; Writing Committee; Sammons E, Hopewell JC, Chen F, Stevens W, Wallendszus K, Valdes-Marquez E, Dayanandan R, Knott C, Murphy K, Wincott E, Baxter A, Goodenough R, Lay M, Hill M, Macdonnell S, Fabbri G, Lucci D, Faja — View Citation

REVEAL Collaborative Group; Bowman L, Chen F, Sammons E, Hopewell JC, Wallendszus K, Stevens W, Valdes- Marquez E, Wiviott S, Cannon CP, Braunwald E, Collins R, Landray MJ. Randomized Evaluation of the Effects of Anacetrapib through Lipid-modification (REVEAL)-A large-scale, randomized, placebo-controlled trial of the clinical effects of anacetrapib among people with established vascular disease: Trial design, recruitment, and baseline characteristics. Am Heart J. 2017 May;187:182-190. doi: 10.1016/j.ahj.2017.02.021. Epub 2017 Feb 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Major Coronary Event	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	Number of Participants With Major Atherosclerotic Event	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
Secondary	Number of Participants With Presumed Ischaemic Stroke	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
Secondary	Number of Participants With Major Vascular Event	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

External Links

•   REVEAL trial website