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See also:

  • All cardiovascular prevention clinical trials
  • All clinical trials of cholesterol lowering intervention
  • All clinical trials of ezetimibe+simvastatin
  •  
     SHARP study, 2010 TRC8081 
    [NCT00125593] download pdf: ezetimibe+simvastatin | cholesterol lowering intervention for cardiovascular prevention

    Treatments

    Studied treatment Simvastatin 20mg/Ezetimibe 10mg
    Control treatment placebo
    Remarks 3 arms: Simvastatin 20 mg, Simvastatin 20mg/Ezetimibe 10mg and placebo

    Patients

    Patients patients with established chronic kidney disease (dialysis or pre-dialysis)
    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 (haemodialysis or peritoneal dialysis); men or women aged greater than or equal to 40 years
    Exclusion criteria definite 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)

    Method and design

    Randomized effectives 4193 / 4191 (studied vs. control)
    Design Parallel groups
    Blinding double-blind
    Follow-up duration 4.9 years
    Number of centre 300
    Geographic area 20 countries
    Hypothesis Superiority
    Primary endpoint vascular events: cardiac death, MI, any stroke, or any revascularization
    Remarks 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


    Results

    Endpoint Studied treat.
    n/N
    Control treat.
    n/N
    Graph RR [95% CI]

    Coronary event

    213 / 4650
    230 / 4620
    0,92 [0,77;1,10]

    End stage renal disease

    1057 / 4650
    1084 / 4620
    0,97 [0,90;1,04]

    Fatal stroke

    68 / 4650
    78 / 4620
    0,87 [0,63;1,20]

    All cause death

    1142 / 4650
    1115 / 4620
    1,02 [0,95;1,09]

    Cancer

    438 / 4650
    439 / 4620
    0,99 [0,87;1,12]

    cardiovascular events

    710 / 4650
    814 / 4620
    0,87 [0,79;0,95]
    0 2 1.0

    Relative risks
    Endpoint Events (%) Relative Risk 95% CI Endpoint definition
    in the trial
    Ref
    Studied treat. Control treat.
    Coronary event 213 / 4650 (4,6%) 230 / 4620 (5,0%) 0,92 [0,77;1,10]  
    End stage renal disease 1057 / 4650 (22,7%) 1084 / 4620 (23,5%) 0,97 [0,90;1,04]  
    Fatal stroke 68 / 4650 (1,5%) 78 / 4620 (1,7%) 0,87 [0,63;1,20]  
    All cause death 1142 / 4650 (24,6%) 1115 / 4620 (24,1%) 1,02 [0,95;1,09]  
    Cancer 438 / 4650 (9,4%) 439 / 4620 (9,5%) 0,99 [0,87;1,12] Any incident cancer  
    cardiovascular events 710 / 4650 (15,3%) 814 / 4620 (17,6%) 0,87 [0,79;0,95] cardiac death, MI, any stroke, or any revascularization 
    The primary endpoint (if exists) appears in blod characters
    Reference(s) used for data extraction:

    Endpoint studied treat. control treat. mean diff

    Absolute risk reduction (for a follow-up of 4.9 years)
    Endpoint Events rate Absolute risk
    reduction (ARR)
    Studied treat. Control treat.
    Coronary event 4,58% 4,98% -0,40%
    End stage renal disease 22,73% 23,46% -0,73%
    Fatal stroke 1,46% 1,69% -0,23%
    All cause death 24,56% 24,13% 0,42%
    Cancer 9,42% 9,50% -0,08%
    cardiovascular events 15,27% 17,62% -2,35%

    Meta-analysis of all similar trials:

    cholesterol lowering intervention in cardiovascular prevention for all chronical situations

    cholesterol lowering intervention in cardiovascular prevention for patients with renal insufficiency (on hemodialysis or transplant)



    Reference(s)

    TrialResults-center ID TRC8081
    Trials register # NCT00125593
    Study web site link http://www.ctsu.ox.ac.uk/~sharp/
    • 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 - 10.1016/j.ahj.2010.08.012
      Pubmed | Hubmed | Fulltext
    • 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 - 10.1016/S0140-6736(11)60739-3
      Pubmed | Hubmed | Fulltext

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