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 - REVEA

Phase 1

• Conditions: Atherosclerotic cardiovascular disease; MedDRA version: 13.1 Level: LLT Classification code 10051615 Term: Atherosclerotic cardiovascular disease System Organ Class: 10047065 - Vascular disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2010-023467-18-FI
• Lead Sponsor: niversity of Oxford

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-06-14
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 30449

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 noncoronary
revascularization, including aortic aneurysm repair or graft); or
• Diabetes mellitus with other evidence of symptomatic coronary heart disease (i.e. treatment or hospitalisation for
angina, or a history of coronary revascularization or acute coronary syndrome).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15000

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 Runin (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. ALT >2x 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, dialysis or functioning renal transplant);
• Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or 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;
(ii) fibric acid derivative (fibrate, including gemfibrozil); or
(iii) niacin (nicotinic acid) at doses above 100mg daily;
• Concurrent treatment with a medication that is contraindicated with anacetrapib or atorvastatin:
(i) any potent CYP3A4 inhibitor, such as:
(a) macrolide antibiotics (erythromycin, clarithromycin, telithromycin);
(b) daptomycin
(c) systemic imidazole or triazole antifungals (e.g. itraconazole, posaconazole);
(d) protease inhibitors (e.g. atazanavir);
(e) nefazodone
(ii) ciclosporin
(iii) systemic use of fusidic acid
Note: Individuals who are taking such drugs temporarily may be rescreened 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 nonmelanoma skin cancer; or recent history of alcohol or substance misuse);
• Women of childbearing 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 on the highest atorvastatin dose (80 mg daily).

In addition, individuals will be excluded at the Randomization visit if any of the following are true:
• Total cholesterol (on desktop analyser) above 4 mmol/L
• Noncompliant with run-in treatment (<90% scheduled run-in medication taken)
• Individual is no longer willing to be randomized into the 45 year trial
• The individual’s doctor is of the view that their patient should not be randomized.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): Unrefuted major coronary event ;Timepoint(s) of evaluation of this end point: After a median follow-up of at least 4 years;Main Objective: The primary objective is to assess the effect of lipid modification using anacetrapib 100mg daily versus placebo on the time to first major coronary event (defined as the occurrence of coronary death, myocardial infarction or coronary revascularization procedure) during the scheduled treatment period.;<br> Secondary Objective: Secondary objectives include assessment of the effects of allocation to anacetrapib versus placebo on:<br> (i) Coronary death or myocardial infarction (key secondary outcome);<br> (ii) Coronary revascularization procedure;<br> (iii) Presumed ischaemic stroke (i.e. not known to be haemorrhagic); and<br> (iv) Death from all cardiovascular causes.<br>

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): Coronary death<br> Myocardial infarction<br> Coronary revasculazation procedure<br> Presumed ischaemic stroke (i.e. not known to be haemorrhagic)<br> Death from all cardiovascular causes<br> ;Timepoint(s) of evaluation of this end point: After a median follow-up of at least 4 years