REVEAL Trial

# 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

# Objective
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

# Sponsor
University of Oxford

# Timeline
The previous information was derived from ClinicalTrials.gov on 09/20/2013 using the identification number NCT01252953.

# Study Description
The previous information was derived from ClinicalTrials.gov on 09/20/2013 using the identification number NCT01252953.

# Eligibility Criteria

## 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).
- 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))
Individuals with a history of acute hepatitis are eligible provided this ALT limit is not exceeded
Severe renal insufficiency (i.e. creatinine >200 mol/L , 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
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
Fibric acid derivative ("fibrate", including gemfibrozil)
niacin (nicotinic acid) at doses above 100 mg daily
Concurrent treatment with a medication that is contraindicated with anacetrapib or atorvastatin
any potent CYP3A4 inhibitor, such as
macrolide antibiotics (erythromycin, clarithromycin, telithromycin)
systemic imidazole or triazole antifungals (e.g. itraconazole, posaconazole)
protease inhibitors (e.g. atazanavir)
nefazodone
ciclosporin
daptomycin
systemic use of fusidic acid (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
- 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))
- Individuals with a history of acute hepatitis are eligible provided this ALT limit is not exceeded
- Severe renal insufficiency (i.e. creatinine >200 mol/L , 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
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
Fibric acid derivative ("fibrate", including gemfibrozil)
niacin (nicotinic acid) at doses above 100 mg daily
- 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
- Fibric acid derivative ("fibrate", including gemfibrozil)
- niacin (nicotinic acid) at doses above 100 mg daily
- Concurrent treatment with a medication that is contraindicated with anacetrapib or atorvastatin
any potent CYP3A4 inhibitor, such as
macrolide antibiotics (erythromycin, clarithromycin, telithromycin)
systemic imidazole or triazole antifungals (e.g. itraconazole, posaconazole)
protease inhibitors (e.g. atazanavir)
nefazodone
ciclosporin
daptomycin
systemic use of fusidic acid (Individuals who are taking such drugs temporarily may be re-screened when they discontinue them, if considered appropriate)
- any potent CYP3A4 inhibitor, such as
macrolide antibiotics (erythromycin, clarithromycin, telithromycin)
systemic imidazole or triazole antifungals (e.g. itraconazole, posaconazole)
protease inhibitors (e.g. atazanavir)
nefazodone
ciclosporin
daptomycin
systemic use of fusidic acid (Individuals who are taking such drugs temporarily may be re-screened when they discontinue them, if considered appropriate)
- macrolide antibiotics (erythromycin, clarithromycin, telithromycin)
- systemic imidazole or triazole antifungals (e.g. itraconazole, posaconazole)
- protease inhibitors (e.g. atazanavir)
- nefazodone
- ciclosporin
- daptomycin
- systemic use of fusidic acid (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 
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
- Total cholesterol above 4 mmol/L 
- 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

# Outcomes

## Primary Outcomes
Major coronary events (defined as coronary death, myocardial infarction or coronary revascularization procedure)  
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.

## Secondary Outcomes
Not provided

# Publications

## Results
Pending

## Conclusion
Pending