Study of Heart and Renal Protection
Condition: Kidney Disease, Chronic
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Chronic Disease
Intervention: Simvastatin 20 mg; Ezetimibe 10mg; Placebo
Intervention description: Once daily; Once daily; Once daily
Intervention MeSH terms: Simvastatin; Ezetimibe
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 9438.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Kidney Disease, Chronic; LDL cholesterol; simvastatin; ezetimibe; cardiovascular disease; atherosclerosis

Summary:

      The chief aim of SHARP was to determine whether lowering blood LDL cholesterol with
      simvastatin (20mg) plus ezetimibe (10mg) daily could safely reduce the risk of coronary heart
      disease, non-hemorrhagic stroke and the need for revascularization procedures in patients
      with chronic kidney disease (CKD). It also aimed to assess whether lowering LDL cholesterol
      reduced the rate of loss of renal function in people with CKD who had not commenced dialysis
      treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  History of chronic kidney disease (CKD): either patients who are pre-dialysis (with a
             plasma or serum creatinine greater than or equal to 150 micromol/l [greater than or
             equal to 1.7 mg/dl] in men, or greater than or equal to 130 micromol/l [greater than
             or equal to 1.5 mg/dl] in women); or patients on dialysis (hemodialysis or peritoneal
             dialysis)

          -  Men or women aged greater than or equal to 40 years

        Exclusion Criteria:

          -  Definite history of myocardial infarction or coronary revascularization procedure

          -  Functioning renal transplant, or living donor-related transplant planned

          -  Less than 2 months since presentation as an acute uraemic emergency (but could be
             entered later, if appropriate)

          -  Definite history of chronic liver disease, or abnormal liver function (i.e. alanine
             aminotransferase [ALT] greater than 1.5 x upper limit of normal [ULN] or, if ALT not
             available, aspartate aminotransferase [AST] greater than 1.5 x ULN). (Note: Patients
             with a history of hepatitis were eligible provided these limits were not exceeded.)

          -  Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis),
             or creatine kinase (CK) greater than 3 x ULN

          -  Definite previous adverse reaction to a statin or to ezetimibe

          -  Concurrent treatment with a contraindicated drug. (Note: Patients who were temporarily
             taking such drugs could have been re-screened for participation in the study when they
             discontinued them, if appropriate.) These contraindicated drugs included: HMG-CoA
             reductase inhibitor ("statin"); fibric acid derivative ("fibrate"); nicotinic acid;
             macrolide antibiotic (erythromycin, clarithromycin); systemic use of imidazole or
             triazole antifungals (e.g. itraconazole, ketoconazole); protease-inhibitors (e.g.
             antiretroviral drugs for HIV infection); nefazodone; ciclosporin

          -  Child-bearing potential (i.e. premenopausal woman who was not using a reliable method
             of contraception)

          -  Known to be poorly compliant with clinic visits or prescribed medication

          -  Medical history that might have limited the individual's ability to take trial
             treatments for the duration of the study (e.g. severe respiratory disease, history of
             cancer other than non-melanoma skin cancer, or recent history of alcohol or substance
             misuse)