Study of Heart and Renal Protection

• Status: Completed
• Trial end date: 2010-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Oxford
• Collaborators: British Heart Foundation; Medical Research Council; Merck Sharp & Dohme Corp.; National Health and Medical Research Council, Australia; Schering-Plough
• Treatments: Ezetimibe; Simvastatin

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)