Randomized evaluation of the effects of anacetrapib through lipid-modificatio

Phase 3

• Conditions: Atherosclerotic cardiovascular disease; Circulatory System; Heart disease

• Registration Number: ISRCTN48678192
• Lead Sponsor: niversity of Oxford (UK)

Brief Summary

2017 Other publications in https://www.ncbi.nlm.nih.gov/pubmed/28454801 design, recruitment, and baseline characteristics 2017 Results article in https://www.ncbi.nlm.nih.gov/pubmed/28847206 results 2019 Results article in https://www.ncbi.nlm.nih.gov/pubmed/31331193 results (added 25/07/2019) 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/34910136/ longer-term follow-up results (added 01/02/2022) 2023 Results article in https://pubmed.ncbi.nlm.nih.gov/37750555/ Immediate- and longer-term impacts of new vascular and nonvascular events on QoL and hospital costs (added 27/09/2023)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-11-18
• Last Update Posted: 9 October 2023
• Study Completion: 2037-01-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 30449

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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.