SHARP, 2010 trial summary

A randomised clinical trial investigating the effect of ezetimibe+simvastatin versus placebo in patients with established chronic kidney disease (dialysis or pre-dialysis)

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NCT00125593    Lancet 2011 Jun 25;377:2181-2192  



Studied treatment Simvastatin 20mg/Ezetimibe 10mg
Control treatment placebo

3 arms: Simvastatin 20 mg, Simvastatin 20mg/Ezetimibe 10mg and placebo



Patients patients with established chronic kidney disease (dialysis or pre-dialysis)
Group sizes4193 / 4191
Inclusion criteriahistory 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 (haemodialysis or peritoneal dialysis); men or women aged greater than or equal to 40 years
Exclusion criteriadefinite history of myocardial infarction or coronary revascularisation procedure; functioning renal transplant, or living donor-related transplant planned; less than 2 months since presentation as an acute uraemic emergency; definite history of chronic liver disease, or abnormal liver function (i.e. alanine aminotransferase [ALT] > 1.5 x upper limit of normal [ULN] or, if ALT not available, aspartate aminotransferase [AST] > 1.5 x ULN); evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or creatinine kinase (CK) >3 x ULN; definite previous adverse reaction to a statin or to ezetimibe; concurrent treatment with a contraindicated drug (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; 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 other than non-melanoma skin cancer, or recent history of alcohol or substance misuse)



Blindness double-blind Inclusion period
Follow-up duration 4.9 years Centers 300
Lost to FU geographical localisation 20 countries
Primary endpoint vascular events: cardiac death, MI, any stroke, or any revascularization Design Parallel groups
HypotheseSuperiority

There is a certain incertitude concerning the primary endpoint (apparently changed by the Steering committe before the trial ended but this change was not endorsed by the sponsor) Statistical analysis plan is not clear too, with or without the inclusion of patients initially allocated to simvastatin alone and re-randomized to either combination or placebo for the remainder of the study period



EndpointX1N1X0N0TE95% CI fatal stroke 68 4650 78 4620 0,87[0,62; 1,20] Death from cardiovascular causes - 4193 - 4191 no data all cause death or CV event - 4193 - 4191 no data Major coronary event 213 4650 230 4620 0,92[0,76; 1,11] End-stage renal disease (ESRD) 1057 4650 1084 4620 0,97[0,88; 1,07] Death from coronary heart disease - 4193 - 4191 no data all cause mortality 1142 4650 1115 4620 1,02[0,93; 1,12] Any incident cancer 438 4650 439 4620 0,99[0,86; 1,14] stroke - 4193 - 4191 no data CV events (fatal and non fatal) 710 4650 814 4620 0,87[0,78; 0,97] cancer 438 4650 439 4620 0,99[0,86; 1,14]0,22,01,0

Sharp Collaborative Group Study of Heart and Renal Protection (SHARP): Randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease. Am Heart J 2010 Nov;160:785-794.e10     [PMID: 21095263]   link to pdf   add to Mendeley  

Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, Wanner C, Krane V, Cass A, Craig J, Neal B, Jiang L, Hooi LS, Levin A, Agodoa L, Gaziano M, Kasiske B, Walker R, Massy ZA, Feldt-Rasmussen B, Krairittichai U, Ophascharoensuk V, Fellström B The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011 Jun 25;377:2181-2192     [PMID: 21663949]   link to pdf   add to Mendeley  

Links

The Heart

ClinicalTrial.gov record NCT00125593



Registering number NCT00125593 (see trial on clinicaltrials.gov)
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