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11 February 2012
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| [ Print-friendly version ] |
| Study of Heart And Renal Protection |
| ISRCTN | ISRCTN54137607 |
| ClinicalTrials.gov identifier | NCT00125593 |
| Public title | Study of Heart And Renal Protection |
| Scientific title | A randomised controlled trial of ezetimibe and simvastatin versus placebo to reduce low density lipoprotein cholesterol in patients with chronic kidney disease |
| Acronym | SHARP |
| Serial number at source | CTSU SHARP 1 |
| Study hypothesis |
Reducing low density lipoprotein (LDL) cholesterol will reduce the risk of major vascular events in patients with chronic kidney disease and may delay progression to end-stage renal disease.
Protocol can be found at: http://www.ctsu.ox.ac.uk/~sharp/download_protocol_en_v5.pdf Please note that as of 10/02/2009 this record was updated to include an amended anticipated end date of 31/08/2010. The initial anticipated end date was 31/07/2010. As of 28/09/2010 the anticipated end date was once again extended (see relevant field). |
| Lay summary | http://www.ctsu.ox.ac.uk/~sharp/QandA_background.htm |
| Ethics approval | Added 10/02/2009: Thames Valley MREC (Multicentre Research Ethics Committee) gave approval on 25th April 2003 (ref: 02/12/022) |
| Study design | Randomised controlled trial |
| Countries of recruitment | Australia, Austria, Canada, China, Czech Republic, Denmark, Finland, France, Germany, Malaysia, Netherlands, New Zealand, Norway, Poland, Sweden, Thailand, United Kingdom, United States of America |
| Disease/condition/study domain | Prevention of vascular disease in chronic kidney disease patients |
| Participants - inclusion criteria |
1. History of chronic kidney disease (CKD): either patients who are pre-dialysis (with a plasma or serum creatinine greater than or equal to 150 µ/l [greater than or equal to 1.7 mg/dl] in men, or greater than or equal to 130 µ/l [greater than or equal to 1.5 mg/dl] in women); or patients on dialysis (haemodialysis or peritoneal dialysis)
2. Men or women aged greater than or equal to 40 years |
| Participants - exclusion criteria |
1. Definite history of myocardial infarction or coronary revascularisation procedure
2. Functioning renal transplant, or living donor-related transplant planned 3. Less than 2 months since presentation as an acute uraemic emergency (but may be entered later, if appropriate) 4. 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). (Note: Patients with a history of hepatitis are eligible provided these limits are not exceeded). 5. Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or creatine kinase (CK) >3 x ULN 6. Definite previous adverse reaction to a statin or to ezetimibe 7. Concurrent treatment with a contraindicated drug (Note: Patients who are temporarily taking such drugs may be re-screened for participation in the study when they discontinue them, if appropriate). These contraindicated drugs include: a. HMG-CoA reductase inhibitor ('statin') b. Fibric acid derivative ('fibrate') c. Nicotinic acid d. Macrolide antibiotic (erythromycin, clarithromycin) e. Systemic use of imidazole or triazole antifungals (e.g. itraconazole, ketoconazole) f. Protease-inhibitors (e.g. antiretroviral drugs for human immunodeficiency virus [HIV] infection) g. Nefazodone h. Ciclosporin 8. Child-bearing potential (i.e. premenopausal woman who is not using a reliable method of contraception) 9. Known to be poorly compliant with clinic visits or prescribed medication 10. 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) |
| Anticipated start date | 01/06/2003 |
| Anticipated end date | 02/09/2010 |
| Status of trial | Completed |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | 9000 (Actual number recruited: 9438; last patient visit on 19/08/2010). |
| Interventions |
Following a 6-week run-in phase, participants are initially randomised to:
Arm 1: placebo, OR Arm 2: Ezetimibe 10 mg + simvastatin 20 mg daily, OR Arm 3: Simvastatin 20 mg daily (1 year only of treatment with simvastatin, then re-randomisation of Arm 3 participants to placebo [Arm 3a] or ezetimibe + simvastatin [Arm 3b] Follow-up is scheduled to continue until all participants have been followed up for at least 4 years, regardless of whether they are continuing to take study treatment. |
| Primary outcome measure(s) |
Major vascular events (defined as non-fatal myocardial infarction or cardiac death, non-fatal or fatal stroke, or revascularisation) at end of study
Please note, in October 2009, the Steering Committee decided to change the primary outcome to major atherosclerotic events, defined as the combination of MI, coronary death, ischaemic stroke, or any revascularization procedure (ie, exclusion of non-coronary cardiac deaths and strokes confirmed to be haemorrhagic from the original major vascular event outcome). The independent sponsor (University of Oxford) was required by its contract with the main funder (Merck/Schering-Plough) to seek its formal agreement to any protocol change, but the funder declined to approve the changes agreed by the Steering Committee. Although it was therefore not possible to revise the protocol accordingly, the Steering Committee was free to change the statistical analysis plan as it considered appropriate whilst it remained blind to the effects of treatment on efficacy end points. The ‘key outcome’ was therefore changed to ‘Major Atherosclerotic Events’ by the Steering Committee whilst still blind to the effects of treatment on clinical outcomes. This is described in the following paper: SHARP Collaborative Group. Study of Heart and Real 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; 160: 785-94 (http://www.ncbi.nlm.nih.gov/pubmed/21095263). |
| Secondary outcome measure(s) |
1. Major vascular events at end of study
2. Major cardiac events (non-fatal myocardial infarction [MI] or cardiac death) at end of study 3. Stroke (fatal or non-fatal) at end of study 4. Coronary or non-coronary revascularisation at end of study 5. Mortality, both overall and within particular categories at end of study 6. Hospital admission for angina at end of study 7. End-stage renal disease (need for long-term dialysis or transplantation) at end of study 8. End-stage renal disease or death from any cause at end of study |
| Sources of funding | Merck Schering-Plough (UK) |
| Trial website | http://www.ctsu.ox.ac.uk/~sharp/ |
| Publications |
1. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/21095263
2. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21663949 |
| Contact name | Prof Colin Baigent |
| Address |
CTSU
Richard Doll Building Old Road Campus Roosevelt Drive |
| City/town | Oxford |
| Zip/Postcode | OX3 7LF |
| Country | United Kingdom |
| Tel | +44 (0)1865 743 743 |
| Fax | +44 (0)1865 743985 |
| sharpclinical@ctsu.ox.ac.uk | |
| Sponsor | University of Oxford (UK) |
| Address |
University Offices
Wellington Square |
| City/town | Oxford |
| Zip/Postcode | OX1 2JD |
| Country | United Kingdom |
| sharp@ctsu.ox.ac.uk | |
| Sponsor website: | http://www.ox.ac.uk/ |
| Date applied | 20/12/2004 |
| Last edited | 06/09/2011 |
| Date ISRCTN assigned | 31/01/2005 |
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| © 2012 ISRCTN unless otherwise stated. | |
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