Study of Heart And Renal Protection

ISRCTN	ISRCTN54137607
DOI	https://doi.org/10.1186/ISRCTN54137607
ClinicalTrials.gov (NCT)	NCT00125593
Clinical Trials Information System (CTIS)	2004-001156-37
Protocol serial number	CTSU SHARP 1
Sponsor	University of Oxford (UK)
Funder	Merck Schering-Plough (UK)

Submission date: 20/12/2004
Registration date: 31/01/2005
Last edited: 31/10/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.ctsu.ox.ac.uk/~sharp/QandA_background.htm

Contact information

Prof Colin Baigent
Scientific

CTSU
Richard Doll Building
Old Road Campus
Roosevelt Drive
Oxford
OX3 7LF
United Kingdom

Phone	+44 (0)1865 743 743
Email	sharpclinical@ctsu.ox.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A randomised controlled trial of ezetimibe and simvastatin versus placebo to reduce low density lipoprotein cholesterol in patients with chronic kidney disease
Study acronym	SHARP
Study objectives	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(s)	Thames Valley MREC (Multicentre Research Ethics Committee), 25/04/2003, ref: 02/12/022
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Ezetimibe, simvastatin
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).
Key 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
Completion date	02/09/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	9000
Key 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
Key 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)
Date of first enrolment	01/06/2003
Date of final enrolment	02/09/2010

Locations

Countries of recruitment

United Kingdom
England
Australia
Austria
Canada
China
Czech Republic
Denmark
Finland
France
Germany
Malaysia
Netherlands
New Zealand
Norway
Poland
Sweden
Thailand
United States of America

Study participating centre

CTSU

Oxford
OX3 7LF
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/11/2010		Yes	No
Results article	results	25/06/2011		Yes	No
Results article	results	01/05/2017		Yes	No
Protocol article	protocol for 5-year follow-up study	14/10/2019	31/10/2019	Yes	No
Basic results				No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

31/10/2019: Publication reference added.
04/05/2017: Publication reference added.
28/09/2010: The overall trial end date was changed from 31/08/2010 to 02/09/2010.
10/02/2009: The overall trial end date was changed from 31/07/2010 to 31/08/2010.