Atherosclerotic cardiovascular disease Circulatory System Heart disease
Conditions
Interventions
Current interventions as of 19/05/2017:
Anacetrapib 100 mg daily or matching placebo. All participants receive background LDL-lowering with
atorvastatin. Both treatment
Sponsors
University of Oxford (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must be aged at least 50 at the time of initial invitation 2. At least one of the following inclusion criteria must be satisfied: 2.1. History of Myocardial Infarction (MI) 2.2. Cerebrovascular atherosclerotic disease (i.e. history of presumed ischaemic stroke or carotid revascularization) 2.3. Peripheral arterial disease (i.e. history of non-coronary revascularization, including aortic aneurysm repair or graft) 2.4. 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
Exclusion criteria: 1. 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) 2. Planned coronary revascularization procedure within the next 6 months (such individuals may be entered later, if appropriate) 3. 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 4. Severe renal insufficiency (i.e. creatinine >200 µmol/L [2.3 mg/dL], dialysis or functioning renal transplant) 5. Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or CK >3x ULN 6. Previous significant adverse reaction to a statin or anacetrapib 7. Current treatment with any of the following lipid-lowering treatments: 7.1. 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 7.2. Fibric acid derivative ('fibrate', including gemfibrozil) 7.3. Niacin (nicotinic acid) at doses above 100 mg daily 8. Concurrent treatment with a medication that is contraindicated with anacetrapib or atorvastatin: 8.1. Any potent CYP3A4 inhibitor, such as: 8.1.1. Macrolide antibiotics (erythromycin, clarithromycin, telithromycin) 8.1.2. Daptomycin 8.1.3. Systemic imidazole or triazole antifungals (e.g. itraconazole, posaconazole) 8.1.4. Protease inhibitors (e.g. atazanavir) 8.1.5. Nefazodone 8.2. Ciclosporin 8.3. Systemic use of fusidic acid 9. Known to be poorly compliant with clinic visits or prescribed medication 10. 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) 11. Women of child-bearing potential (unless using adequate contraception) 12. Current participation in a clinical trial with an unlicensed drug or device 13. 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). 14. In addition, individuals will be excluded at the Randomization visit if any of the following are true: 14.1. Total cholesterol above 4 mmol/L [155 mg/dL] 14.2. Non-compliant with run-in treatment (<90% scheduled run-in medication taken) 14.3. Individual is no longer willing to be randomized into the 4-5 year trial 14.4. The individual?s doctor is of the view that their patient should not be randomized
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 05/07/2016: Intention-to-treat comparisons among all randomized participants of the effects of allocation to anacetrapib versus placebo during the scheduled treatment period on: 1. Major atherosclerotic events (defined as coronary death, myocardial infarction or presumed ischaemic stroke; the key secondary outcome) 2. Presumed ischaemic stroke (i.e. not known to be haemorrhagic) 3. Major vascular events (defined as coronary death, myocardial infarction, coronary revascularization or presumed ischaemic stroke) In addition, each of the individual components of the primary outcome (i.e. coronary death; myocardial infarction; and coronary revascularization) will be tested separately. Previous secondary outcome measures: Intention-to-treat comparisons among all randomized participants of the effects of allocation to anacetrapib versus placebo during the scheduled treatment period on: 1. Coronary death or myocardial infarction (key secondary outcome) 2. Coronary revascularization procedure 3. Presumed ischaemic stroke (i.e. not known to be haemorrhagic) 4. Death from all cardiovascular causes | — |
Countries
Canada, China, Denmark, England, Finland, Germany, Italy, Norway, Sweden, United Kingdom, United States of America
Outcome results
None listed