ISRCTN ISRCTN54137607
DOI https://doi.org/10.1186/ISRCTN54137607
EudraCT/CTIS number 2004-001156-37
ClinicalTrials.gov number NCT00125593
Secondary identifying numbers CTSU SHARP 1
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

Study website

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

Study designRandomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typePrevention
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleA randomised controlled trial of ezetimibe and simvastatin versus placebo to reduce low density lipoprotein cholesterol in patients with chronic kidney disease
Study acronymSHARP
Study objectivesReducing 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) studiedPrevention of vascular disease in chronic kidney disease patients
InterventionFollowing 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Ezetimibe, simvastatin
Primary outcome measureMajor 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 measures1. 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 study start date01/06/2003
Completion date02/09/2010

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants9000 (actual number recruited: 9438; last patient visit on 19/08/2010)
Key inclusion criteria1. 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 criteria1. 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 enrolment01/06/2003
Date of final enrolment02/09/2010

Locations

Countries of recruitment

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

Study participating centre

CTSU
Oxford
OX3 7LF
United Kingdom

Sponsor information

University of Oxford (UK)
University/education

University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom

Email sharp@ctsu.ox.ac.uk
Website http://www.ox.ac.uk/
ROR logo "ROR" https://ror.org/052gg0110

Funders

Funder type

Industry

Merck Schering-Plough (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Basic results No No
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

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.