Treatment of HDL to Reduce the Incidence of Vascular Events HPS2-THRIVE

• Status: Completed
• Trial end date: 2012-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary aim is to assess the effects of raising HDL cholesterol (the good type) with extended release niacin/laropiprant 2g (previously known as MK-0524A) versus matching placebo on the risk of heart attack or coronary death, stroke, or the need for arterial bypass procedures (revascularisation) in people with a history of circulatory problems. The secondary aim is to assess the effects of extended release niacin/laropiprant 2g daily on heart attack, coronary death, stroke, and revascularisation separately and to assess the effects on mortality both overall and in various categories of causes of death, and of the effects on major cardiovascular events in people with a history of different diseases at the beginning of the study.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Oxford
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Niacin; Niacinamide; Nicotinic Acids; Simvastatin

Criteria

Inclusion Criteria:

• History of myocardial infarction; or

• Cerebrovascular atherosclerotic disease (history of presumed ischaemic stroke, transient ischaemic attack or carotid revascularisation)

• Peripheral arterial disease (i.e. intermittent claudication or history of revascularisation); or

• Diabetes mellitus with any of the above or with other evidence of symptomatic coronary heart disease (i.e. stable or unstable angina, or a history of coronary revascularisation or acute coronary syndrome).

Exclusion Criteria:

• Age <50 or >80 years at invitation to Screening;

• Less than 3 months since presentation with acute myocardial infarction, coronary syndrome or stroke (but such patients may be entered later, if appropriate);

• Planned revascularisation procedure within 3 months after randomization (but such patients may be entered later, if appropriate);

• Definite history of chronic liver disease, or abnormal liver function (i.e. Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN). (Note: Patients with a history of acute hepatitis are eligible provided this ALT limit is not exceeded);

• Breathlessness at rest for any reason;

• Severe renal insufficiency (i.e. creatinine >200 µmol/L);

• Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or Creatine kinase (CK) >3 times upper limit of normal (3xULN);

• Previous significant adverse reaction to a statin, ezetimibe, niacin or laropiprant;

• Active peptic ulcer disease;

• Concurrent treatment with:

• fibric acid derivative ("fibrate")

• niacin (nicotinic acid) at doses more than 100 mg daily

• ezetimibe in combination with either simvastatin 80 mg, or atorvastatin 20-80 mg, or rosuvastatin 10-40 mg daily

• any potent cytochrome P450 3A4 (CYP3A4) inhibitor, including: macrolide antibiotics (erythromycin, clarithromycin, telithromycin); systemic use of imidazole or triazole antifungals (e.g. itraconazole, ketoconazole); protease inhibitors (antiretroviral drugs for HIV infection); and nefazodone

• ciclosporin

• amiodarone

• verapamil

• danazol (Note: Patients who are temporarily taking such drugs 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)