Contact information
Type
Scientific
Primary contact
Prof Colin Baigent
ORCID ID
Contact details
CTSU
Richard Doll Building
Old Road Campus
Roosevelt Drive
Oxford
OX3 7LF
United Kingdom
+44 (0)1865 743 743
sharpclinical@ctsu.ox.ac.uk
Additional identifiers
EudraCT number
2004-001156-37
ClinicalTrials.gov number
NCT00125593
Protocol/serial number
CTSU SHARP 1
Study information
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
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
Ethics approval
Thames Valley MREC (Multicentre Research Ethics Committee), 25/04/2003, ref: 02/12/022
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Prevention
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Prevention of vascular disease in chronic kidney disease patients
Intervention
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.
Intervention type
Drug
Phase
Not Applicable
Drug names
Ezetimibe, simvastatin
Primary outcome measure
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 measures
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
Overall trial start date
01/06/2003
Overall trial end date
02/09/2010
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
9000 (actual number recruited: 9438; last patient visit on 19/08/2010)
Participant 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)
Recruitment start date
01/06/2003
Recruitment end date
02/09/2010
Locations
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
Trial participating centre
CTSU
Oxford
OX3 7LF
United Kingdom
Sponsor information
Organisation
University of Oxford (UK)
Sponsor details
University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom
-
sharp@ctsu.ox.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Industry
Funder name
Merck Schering-Plough (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
See https://clinicaltrials.gov/ct2/show/results/NCT00125593
Publication list
2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/21095263
2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/21663949
2017 results in: http://www.ncbi.nlm.nih.gov/pubmed/28460629
Publication citations
-
Results
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, 160, 5, 785-794.e10, doi: 10.1016/j.ahj.2010.08.012.
-
Results
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, Holdaas H, Tesar V, Wiecek A, Grobbee D, de Zeeuw D, Grönhagen-Riska C, Dasgupta T, Lewis D, Herrington W, Mafham M, Majoni W, Wallendszus K, Grimm R, Pedersen T, Tobert J, Armitage J, Baxter A, Bray C, Chen Y, Chen Z, Hill M, Knott C, Parish S, Simpson D, Sleight P, Young A, Collins R, , 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, 377, 9784, 2181-2192, doi: 10.1016/S0140-6736(11)60739-3.