Treatment of HDL to Reduce the Incidence of Vascular Events HPS2-THRIVE
Condition: Cardiovascular Disease; Peripheral Arterial Disease; Diabetes Mellitus; Coronary Heart Disease
MeSH terms: Cardiovascular Diseases; Heart Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Diabetes Mellitus
Intervention: ER niacin/laropiprant; simvastatin; ezetimibe/simvastatin
Intervention description: 40 mg simvastatin tablet orally per day as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level; 10 mg ezetimibe plus 40 mg simvastatin in single tablet taken once daily as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level
Intervention MeSH terms: Niacin; Simvastatin; Ezetimibe; Ezetimibe, Simvastatin Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 25673.0
Sex: All
Minimum age: 50 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: coronary heart disease; cardiovascular disease; stroke; peripheral arterial disease; diabetes mellitus; cholesterol; HDL cholesterol; simvastatin; ezetimibe; ER niacin; laropiprant

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.
    

Eligibility 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)