Condition category
Circulatory System
Date applied
20/12/2004
Date assigned
31/01/2005
Last edited
23/10/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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 below 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 measures

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

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

http://www.ox.ac.uk/

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

Results - basic reporting

See https://clinicaltrials.gov/ct2/show/results/NCT00125593

Publication summary

1. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/21095263
2. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21663949

Publication citations

  1. 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.

  2. 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.

Additional files

Editorial Notes

Please note that as of 10/02/2009 this record was updated to include an amended overall trial end date of 31/08/2010. The initial overall trial end date was 31/07/2010. As of 28/09/2010 the overall trial end date was once again extended (see relevant field).