Kidney Disease, ChronicPhase 4SHARPNCT00125593

Study of Heart and Renal Protection

A Phase 4 study testing Simvastatin 20 mg and Ezetimibe 10mg in people with Kidney Disease, Chronic, run by University of Oxford at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The chief aim of SHARP was to determine whether lowering blood LDL cholesterol with simvastatin (20mg) plus ezetimibe (10mg) daily could safely reduce the risk of coronary heart disease, non-hemorrhagic stroke and the need for revascularization procedures in patients with chronic kidney disease (CKD). Read more about this study

Who is it for?: Ages 40 years and older
Conditions the study is for: Kidney Disease, Chronic
What is being tested?: Simvastatin 20 mg and Ezetimibe 10mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 9,438 participants
Where: 1 siteUnited Kingdom
Study dates: Jun 2003to Aug 2010
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

History of chronic kidney disease (CKD): either patients who are pre-dialysis (with a plasma or serum creatinine greater than or equal to 150 micromol/l [greater than or equal to 1.7 mg/dl] in men, or greater than or equal to 130 micromol/l [greater than or equal to 1.5 mg/dl] in women); or patients on dialysis (hemodialysis or peritoneal dialysis)
Men or women aged greater than or equal to 40 years

Who cannot join

Definite history of myocardial infarction or coronary revascularization procedure
Functioning renal transplant, or living donor-related transplant planned
Less than 2 months since presentation as an acute uraemic emergency (but could be entered later, if appropriate)
Definite history of chronic liver disease, or abnormal liver function (i.e. alanine aminotransferase [ALT] greater than 1.5 x upper limit of normal [ULN] or, if ALT not available, aspartate aminotransferase [AST] greater than 1.5 x ULN). (Note: Patients with a history of hepatitis were eligible provided these limits were not exceeded.)
Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or creatine kinase (CK) greater than 3 x ULN
Definite previous adverse reaction to a statin or to ezetimibe

Show all 10Show fewer

Concurrent treatment with a contraindicated drug. (Note: Patients who were temporarily taking such drugs could have been re-screened for participation in the study when they discontinued them, if appropriate.) These contraindicated drugs included: HMG-CoA reductase inhibitor ("statin"); fibric acid derivative ("fibrate"); nicotinic acid; macrolide antibiotic (erythromycin, clarithromycin); systemic use of imidazole or triazole antifungals (e.g. itraconazole, ketoconazole); protease-inhibitors (e.g. antiretroviral drugs for HIV infection); nefazodone; ciclosporin
Child-bearing potential (i.e. premenopausal woman who was not using a reliable method of contraception)
Known to be poorly compliant with clinic visits or prescribed medication
Medical history that might have limited 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)

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford
Oxford, OX3 7LF

Other trials in United Kingdom

About this study

Official title: Study of Heart and Renal Protection (SHARP): The Effects of Lowering LDL-cholesterol With Simvastatin 20mg Plus Ezetimibe 10mg in Patients With Chronic Kidney Disease: a Randomized Placebo-controlled Trial

Read the detailed description

The SHARP (Study of Heart and Renal Protection) was a double-blind placebo-controlled trial which aimed to assess the safety and efficacy of reducing LDL cholesterol in more than 9,000 patients with chronic kidney disease (about 3,000 of whom were on dialysis at randomization).

Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo (a subset of these patients had previously received simvastatin 20mg only and were then randomly re-assigned to receive simvastatin 20mg plus ezetimibe 10mg or placebo at one year). Details of the SHARP trial design and methods have been reported previously (reference: Am Heart J 2010; 160:785-94.).

SHARP was overseen by an independent Steering Committee that included nephrologists, cardiologists, clinical trialists, and statisticians, with 2 non-voting observers from the main funder (Merck/Schering-Plough Pharmaceuticals). The independent sponsor was the University of Oxford, and the trial was funded by Merck/Schering-Plough Pharmaceuticals, the Australian National Health and Medical Research Council, the British Heart Foundation and the UK Medical Research Council.

In October 2009, the Steering Committee decided (blind to the effects of study treatment on clinical outcomes) to change the original protocol-specified primary outcome to a revised key outcome of major atherosclerotic events, defined as the combination of non-fatal myocardial infarction, coronary death, ischemic stroke, or any revascularization procedure (i.e. exclusion of non-coronary cardiac deaths and strokes confirmed to be hemorrhagic from the original major vascular event outcome). These and other changes are described in the revised statistical analysis plan for SHARP (reference: Am Heart J 2010; 160:785-94.). Accordingly, the chief emphasis of the published results (reference: Lancet 2011; 377:2181-92) is on the revised pre-specified key outcome of first major atherosclerotic events.

Conditions: Kidney Disease, Chronic
Being tested: Simvastatin 20 mg, Ezetimibe 10mg, Placebo
Keywords: Kidney Disease, Chronic, LDL cholesterol, simvastatin, ezetimibe, cardiovascular disease, atherosclerosis
Medical subject headings: Renal Insufficiency, Chronic, Cardiovascular Diseases, Atherosclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Simvastatin 20 mgDrug
Also called Zocor
Once daily
Ezetimibe 10mgDrug
Also called Ezetrol, Zetia, Vytorin (simvastatin plus ezetimibe)
Once daily
PlaceboDrug
Once daily

Study groups in NCT00125593
Study group	Role	What they receive
Placebo	Placebo comparator	Placebo = Arm 1. A double-dummy method ensured that patients and study staff were unaware of the treatment allocation, with all Arm 1 patients taking 2 tablets (placebo simvastatin plus ezetimibe tablet with a placebo simvastatin tablet) during the first year. After the first year, all Arm 1 patients took one tablet (placebo simvastatin plus ezetimibe tablet). Receives: Drug: Placebo
Simvastatin 20mg plus Ezetimibe 10mg	Active comparator	Simvastatin 20mg plus ezetimibe 10mg = Arm 2. A double-dummy method ensured that patients and study staff were unaware of the treatment allocation, with all Arm 2 patients taking 2 tablets during the first year (active simvastatin plus ezetimibe tablet with a placebo simvastatin tablet). After the first year, all Arm 2 patients took one tablet (active simvastatin 20mg plus ezetimibe 10mg tablet). Receives: Drug: Simvastatin 20 mg; Drug: Ezetimibe 10mg
Simvastatin 20mg	Other	Simvastatin 20mg alone = Arm 3. After 1 year, those initially allocated to Arm 3 were re-randomized to simvastatin 20mg plus ezetimibe 10mg (Arm 3b) daily or placebo (Arm 3a). A double-dummy method ensured that patients and study staff were unaware of the treatment allocation, with Arm 3 patients taking 2 tablets (a placebo simvastatin plus ezetimibe tablet with an active simvastatin tablet) during the first year. After the first year, all Arm 3a and Arm 3b patients took one tablet (active or placebo simvastatin plus ezetimibe tablet). Receives: Drug: Simvastatin 20 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

Key Outcome as Per Statistical Analysis Plan = Major Atherosclerotic Events Among All Patients Ever Randomized to Simvastatin Plus Ezetimibe Versus All Patients Allocated to Placebo
Major atherosclerotic events defined as non-fatal myocardial infarction or coronary death, non-hemorrhagic stroke, or any arterial revascularization procedure (excluding dialysis access procedures). Numbers provided = number of patients with events.
Measured: Median follow-up 4.9 years

Secondary outcomes (6)

Major Vascular Events Analyzed Among All Patients Ever Randomized to Simvastatin Plus Ezetimibe Versus All Patients Allocated to Placebo
Major vascular events defined as non-fatal myocardial infarction or cardiac death, any stroke, or any arterial revascularization procedure (excluding dialysis access procedures). Numbers provided = number of patients with events.
Measured: Median follow-up 4.9 years
Major Vascular Events Analyzed Amongst Patients Initially Randomized to Simvastatin Plus Ezetimibe Versus Placebo (Original Protocol-defined Primary Outcome)
Major vascular events defined as non-fatal myocardial infarction or cardiac death, any stroke, or any arterial revascularization procedure (excluding dialysis access procedures). Numbers provided = number of patients with events.
Measured: Median follow-up 4.9 years
Major Coronary Events Among All Patients Ever Randomized to Simvastatin Plus Ezetimibe Versus All Patients Allocated to Placebo
Major coronary events defined as coronary death or non-fatal myocardial infarction. Myocardial infarction adjudicated based on the presence of serial changes in cardiac biomarkers (e.g. troponin, creatine kinase), typical ECG changes and typical cardiac symptoms. If myocardial infarction was fatal and post-mortem examination findings were available, this information was also assessed. All potential coronary events were adjudicated, using pre-specified objective criteria, by clinicians blinded to study treatment allocation and lipid levels. Numbers provided = number of patients with events.
Measured: Median follow-up 4.9 years
Non-hemorrhagic Stroke Among All of Patients Ever Randomized to Simvastatin Plus Ezetimibe Versus All Patients Allocated to Placebo
Stroke was defined as rapid onset of focal or global neurological deficit, with duration greater than 24 hours. Clinical notes and brain imaging were sought to determine the stroke etiology, and if the stroke was fatal and post-mortem examination findings were available, this information was also assessed. All potential stroke events (including transient ischemic attack and intracerebral hemorrhage) were adjudicated, using pre-specified objective criteria, by clinicians blinded to study treatment allocation and lipid levels. Numbers provided = number of patients with events.
Measured: Median follow-up 4.9 years
Coronary or Non-coronary Revascularization Among All Patients Ever Randomized to Simvastatin Plus Ezetimibe Versus All Patients Allocated to Placebo
Revascularization included any arterial revascularization procedure, whether surgical or percutaneous, but excluded revascularization performed for hemodialysis vascular access (e.g. fistuloplasty) or to the donor kidney transplant artery. Revascularization included amputations for vascular disease (rather than for trauma or infection). All potential revascularization events (including angiography) were adjudicated, using pre-specified objective criteria, by clinicians blinded to study treatment allocation and lipid levels. Numbers provided = number of patients with events.
Measured: Median follow-up 4.9 years
End-stage Renal Disease Among All Patients Not on Dialysis at the Time of Randomization to Simvastatin Plus Ezetimibe Versus Placebo
End-stage renal disease was defined as initiation of maintenance dialysis or renal transplantation. Temporary dialysis was excluded. All potential dialysis and transplant events were adjudicated, using pre-specified objective criteria, by clinicians blinded to study treatment allocation and lipid levels. Numbers provided = number of patients with events.
Measured: Median follow-up 4.9 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2003Aug 2010

First posted1 Aug 2005 (estimated)
Study startJun 2003
Primary completionAug 2010
Study completionAug 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (12)Papers the sponsor has linked to this study.
Other trials for Kidney Disease, ChronicStudies of the same condition, open and under way.
More trials run by University of OxfordThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 9,438 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00125593
Sponsor's protocol ID: CTSUSHARP1
Other IDs: ISRCTN54137607, EudraCT - 2004-001156-37, UK CRN 2542
Acronym: SHARP
Status last verified: Jan 2012
First submitted: 29 Jul 2005
Last updated: 1 Feb 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Baigent C, Landray M, Leaper C, Altmann P, Armitage J, Baxter A, Cairns HS, Collins R, Foley RN, Frighi V, Kourellias K, Ratcliffe PJ, Rogerson M, Scoble JE, Tomson CR, Warwick G, Wheeler DC. First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease. Am J Kidney Dis. 2005 Mar;45(3):473-84. doi: 10.1053/j.ajkd.2004.11.015.
PubMed 15754269
Landray M, Baigent C, Leaper C, Adu D, Altmann P, Armitage J, Ball S, Baxter A, Blackwell L, Cairns HS, Carr S, Collins R, Kourellias K, Rogerson M, Scoble JE, Tomson CR, Warwick G, Wheeler DC. The second United Kingdom Heart and Renal Protection (UK-HARP-II) Study: a randomized controlled study of the biochemical safety and efficacy of adding ezetimibe to simvastatin as initial therapy among patients with CKD. Am J Kidney Dis. 2006 Mar;47(3):385-95. doi: 10.1053/j.ajkd.2005.11.018.
PubMed 16490616
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 Nov;160(5):785-794.e10. doi: 10.1016/j.ahj.2010.08.012. Epub 2010 Sep 18.
PubMed 21095263
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, Fellstrom B, Holdaas H, Tesar V, Wiecek A, Grobbee D, de Zeeuw D, Gronhagen-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; SHARP Investigators. 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 Jun 25;377(9784):2181-92. doi: 10.1016/S0140-6736(11)60739-3. Epub 2011 Jun 12.
PubMed 21663949
Tunnicliffe DJ, Palmer SC, Cashmore BA, Saglimbene VM, Krishnasamy R, Lambert K, Johnson DW, Craig JC, Strippoli GF. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2023 Nov 29;11(11):CD007784. doi: 10.1002/14651858.CD007784.pub3.
PubMed 38018702
Sukkar L, Talbot B, Jun M, Dempsey E, Walker R, Hooi L, Cass A, Jardine M, Gallagher M. Protocol for the Study of Heart and Renal Protection-Extended Review: Additional 5-Year Follow-up of the Australian, New Zealand, and Malaysian SHARP Cohort. Can J Kidney Health Dis. 2019 Oct 14;6:2054358119879896. doi: 10.1177/2054358119879896. eCollection 2019.
PubMed 31662874
Schlackow I, Kent S, Herrington W, Emberson J, Haynes R, Reith C, Collins R, Landray MJ, Gray A, Baigent C, Mihaylova B; SHARP Collaborative Group. Cost-effectiveness of lipid lowering with statins and ezetimibe in chronic kidney disease. Kidney Int. 2019 Jul;96(1):170-179. doi: 10.1016/j.kint.2019.01.028. Epub 2019 Mar 12.
PubMed 31005271
Schlackow I, Kent S, Herrington W, Emberson J, Haynes R, Reith C, Wanner C, Fellstrom B, Gray A, Landray MJ, Baigent C, Mihaylova B; SHARP Collaborative Group. A policy model of cardiovascular disease in moderate-to-advanced chronic kidney disease. Heart. 2017 Dec;103(23):1880-1890. doi: 10.1136/heartjnl-2016-310970. Epub 2017 Aug 5.
PubMed 28780579
Reith C, Staplin N, Herrington WG, Stevens W, Emberson J, Haynes R, Mafham M, Armitage J, Cass A, Craig JC, Jiang L, Pedersen T, Baigent C, Landray MJ; SHARP Collaborative Group. Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection. BMC Nephrol. 2017 May 1;18(1):147. doi: 10.1186/s12882-017-0545-2.
PubMed 28460629
Herrington W, Staplin N, Judge PK, Mafham M, Emberson J, Haynes R, Wheeler DC, Walker R, Tomson C, Agodoa L, Wiecek A, Lewington S, Reith CA, Landray MJ, Baigent C; SHARP Collaborative Group. Evidence for Reverse Causality in the Association Between Blood Pressure and Cardiovascular Risk in Patients With Chronic Kidney Disease. Hypertension. 2017 Feb;69(2):314-322. doi: 10.1161/HYPERTENSIONAHA.116.08386. Epub 2016 Dec 27.
PubMed 28028192
Morton RL, Schlackow I, Staplin N, Gray A, Cass A, Haynes R, Emberson J, Herrington W, Landray MJ, Baigent C, Mihaylova B; SHARP Collaborative Group. Impact of Educational Attainment on Health Outcomes in Moderate to Severe CKD. Am J Kidney Dis. 2016 Jan;67(1):31-9. doi: 10.1053/j.ajkd.2015.07.021. Epub 2015 Sep 16.
PubMed 26385817
Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R. Analyses of cancer data from three ezetimibe trials. N Engl J Med. 2008 Sep 25;359(13):1357-66. doi: 10.1056/NEJMsa0806603. Epub 2008 Sep 2.
PubMed 18765432

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Study of Heart and Renal Protection (SHARP): The Effects of Lowering LDL-cholesterol With Simvastatin 20mg Plus Ezetimibe 10mg in Patients With Chronic Kidney Disease: a Randomized Placebo-controlled Trial
ClinicalTrials.gov ID: NCT00125593
Acronym / sponsor ID: SHARP / CTSUSHARP1
Conditions: Kidney Disease, Chronic
Keywords: Kidney Disease, Chronic, LDL cholesterol, simvastatin, ezetimibe, cardiovascular disease, atherosclerosis
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 9,438 participants (actual)
Lead sponsor: University of OxfordUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC, Schering-Plough, National Health and Medical Research Council, Australia, British Heart Foundation, Medical Research Council
Study start: Jun 2003
Primary completion: Aug 2010 (actual)
Study completion: Aug 2010 (actual)
First posted: 1 Aug 2005 (estimated)
Results: Posted 1 Feb 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboPlacebo = Arm 1. A double-dummy method ensured that patients and study staff were unaware of the treatment allocation, with all Arm 1 patients taking 2 tablets (placebo simvastatin plus ezetimibe tablet with a placebo simvastatin tablet) during the first year. After the first year, all Arm 1 patients took one tablet (placebo simvastatin plus ezetimibe tablet).
Simvastatin 20mg plus Ezetimibe 10mg	Active comparator	Drug: Simvastatin 20 mg, Drug: Ezetimibe 10mgSimvastatin 20mg plus ezetimibe 10mg = Arm 2. A double-dummy method ensured that patients and study staff were unaware of the treatment allocation, with all Arm 2 patients taking 2 tablets during the first year (active simvastatin plus ezetimibe tablet with a placebo simvastatin tablet). After the first year, all Arm 2 patients took one tablet (active simvastatin 20mg plus ezetimibe 10mg tablet).
Simvastatin 20mg	Other	Drug: Simvastatin 20 mgSimvastatin 20mg alone = Arm 3. After 1 year, those initially allocated to Arm 3 were re-randomized to simvastatin 20mg plus ezetimibe 10mg (Arm 3b) daily or placebo (Arm 3a). A double-dummy method ensured that patients and study staff were unaware of the treatment allocation, with Arm 3 patients taking 2 tablets (a placebo simvastatin plus ezetimibe tablet with an active simvastatin tablet) during the first year. After the first year, all Arm 3a and Arm 3b patients took one tablet (active or placebo simvastatin plus ezetimibe tablet).

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

History of chronic kidney disease (CKD): either patients who are pre-dialysis (with a plasma or serum creatinine greater than or equal to 150 micromol/l [greater than or equal to 1.7 mg/dl] in men, or greater than or equal to 130 micromol/l [greater than or equal to 1.5 mg/dl] in women); or patients on dialysis (hemodialysis or peritoneal dialysis)
Men or women aged greater than or equal to 40 years

Key exclusion criteria (10 listed)

Definite history of myocardial infarction or coronary revascularization procedure
Functioning renal transplant, or living donor-related transplant planned
Less than 2 months since presentation as an acute uraemic emergency (but could be entered later, if appropriate)
Definite history of chronic liver disease, or abnormal liver function (i.e. alanine aminotransferase [ALT] greater than 1.5 x upper limit of normal [ULN] or, if ALT not available, aspartate aminotransferase [AST] greater than 1.5 x ULN). (Note: Patients with a history of hepatitis were eligible provided these limits were not exceeded.)
Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or creatine kinase (CK) greater than 3 x ULN

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Simvastatin 20 mgAlso: ZocorOnce daily	Drug	Simvastatin 20mg, Simvastatin 20mg plus Ezetimibe 10mg
Ezetimibe 10mgAlso: Ezetrol, Zetia, Vytorin (simvastatin plus ezetimibe)Once daily	Drug	Simvastatin 20mg plus Ezetimibe 10mg
PlaceboOnce daily	Drug	Placebo

Primary outcome

Key Outcome as Per Statistical Analysis Plan = Major Atherosclerotic Events Among All Patients Ever Randomized to Simvastatin Plus Ezetimibe Versus All Patients Allocated to Placebo
Time frame: Median follow-up 4.9 years
Major atherosclerotic events defined as non-fatal myocardial infarction or coronary death, non-hemorrhagic stroke, or any arterial revascularization procedure (excluding dialysis access procedures). Numbers provided = number of patients with events.

6 secondary outcomes

Major Vascular Events Analyzed Among All Patients Ever Randomized to Simvastatin Plus Ezetimibe Versus All Patients Allocated to Placebo
Time frame: Median follow-up 4.9 years
Major Vascular Events Analyzed Amongst Patients Initially Randomized to Simvastatin Plus Ezetimibe Versus Placebo (Original Protocol-defined Primary Outcome)
Time frame: Median follow-up 4.9 years
Major Coronary Events Among All Patients Ever Randomized to Simvastatin Plus Ezetimibe Versus All Patients Allocated to Placebo
Time frame: Median follow-up 4.9 years
Non-hemorrhagic Stroke Among All of Patients Ever Randomized to Simvastatin Plus Ezetimibe Versus All Patients Allocated to Placebo
Time frame: Median follow-up 4.9 years
Coronary or Non-coronary Revascularization Among All Patients Ever Randomized to Simvastatin Plus Ezetimibe Versus All Patients Allocated to Placebo
Time frame: Median follow-up 4.9 years
End-stage Renal Disease Among All Patients Not on Dialysis at the Time of Randomization to Simvastatin Plus Ezetimibe Versus Placebo
Time frame: Median follow-up 4.9 years

Results and safety

Results posted to the registry on 1 Feb 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Simvastatin 20mg Plus Ezetimibe 10mg	4,650	4,549
Placebo	4,620	4,517

Primary outcome: Key Outcome as Per Statistical Analysis Plan = Major Atherosclerotic Events Among All Patients Ever Randomized to Simvastatin Plus Ezetimibe Versus All Patients Allocated to Placebo

Time frame: Median follow-up 4.9 years. Number. Unit: participants

Measure	Simvastatin Plus Ezetimibe n = 4650	Placebo n = 4620
Value	526	619

Simvastatin Plus Ezetimibe vs Placebo: Risk Ratio (RR): 0.83 (95% CI 0.74 to 0.94), p = 0.0021, Log Rank

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Median follow-up 4.9 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Simvastatin Plus Ezetimibe	1,142 of 4,650 (24.6%)	992 of 4,650 (21.3%)	Not reported
Placebo	1,115 of 4,620 (24.1%)	960 of 4,620 (20.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 15754269Baigent C, Landray M, Leaper C, Altmann P, Armitage J, Baxter A, Cairns HS, Collins R, Foley RN, Frighi V, Kourellias K, Ratcliffe PJ, Rogerson M, Scoble JE, Tomson CR, Warwick G, Wheeler DC. First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease. Am J Kidney Dis. 2005 Mar;45(3):473-84. doi: 10.1053/j.ajkd.2004.11.015.
Background: PubMed 16490616Landray M, Baigent C, Leaper C, Adu D, Altmann P, Armitage J, Ball S, Baxter A, Blackwell L, Cairns HS, Carr S, Collins R, Kourellias K, Rogerson M, Scoble JE, Tomson CR, Warwick G, Wheeler DC. The second United Kingdom Heart and Renal Protection (UK-HARP-II) Study: a randomized controlled study of the biochemical safety and efficacy of adding ezetimibe to simvastatin as initial therapy among patients with CKD. Am J Kidney Dis. 2006 Mar;47(3):385-95. doi: 10.1053/j.ajkd.2005.11.018.
Background: PubMed 21095263Sharp 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 Nov;160(5):785-794.e10. doi: 10.1016/j.ahj.2010.08.012. Epub 2010 Sep 18.
Results publication: PubMed 21663949Baigent 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, Fellstrom B, Holdaas H, Tesar V, Wiecek A, Grobbee D, de Zeeuw D, Gronhagen-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; SHARP Investigators. 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 Jun 25;377(9784):2181-92. doi: 10.1016/S0140-6736(11)60739-3. Epub 2011 Jun 12.
Derived from this study: PubMed 38018702Tunnicliffe DJ, Palmer SC, Cashmore BA, Saglimbene VM, Krishnasamy R, Lambert K, Johnson DW, Craig JC, Strippoli GF. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2023 Nov 29;11(11):CD007784. doi: 10.1002/14651858.CD007784.pub3.
Derived from this study: PubMed 31662874Sukkar L, Talbot B, Jun M, Dempsey E, Walker R, Hooi L, Cass A, Jardine M, Gallagher M. Protocol for the Study of Heart and Renal Protection-Extended Review: Additional 5-Year Follow-up of the Australian, New Zealand, and Malaysian SHARP Cohort. Can J Kidney Health Dis. 2019 Oct 14;6:2054358119879896. doi: 10.1177/2054358119879896. eCollection 2019.
Derived from this study: PubMed 31005271Schlackow I, Kent S, Herrington W, Emberson J, Haynes R, Reith C, Collins R, Landray MJ, Gray A, Baigent C, Mihaylova B; SHARP Collaborative Group. Cost-effectiveness of lipid lowering with statins and ezetimibe in chronic kidney disease. Kidney Int. 2019 Jul;96(1):170-179. doi: 10.1016/j.kint.2019.01.028. Epub 2019 Mar 12.
Derived from this study: PubMed 28780579Schlackow I, Kent S, Herrington W, Emberson J, Haynes R, Reith C, Wanner C, Fellstrom B, Gray A, Landray MJ, Baigent C, Mihaylova B; SHARP Collaborative Group. A policy model of cardiovascular disease in moderate-to-advanced chronic kidney disease. Heart. 2017 Dec;103(23):1880-1890. doi: 10.1136/heartjnl-2016-310970. Epub 2017 Aug 5.
Derived from this study: PubMed 28460629Reith C, Staplin N, Herrington WG, Stevens W, Emberson J, Haynes R, Mafham M, Armitage J, Cass A, Craig JC, Jiang L, Pedersen T, Baigent C, Landray MJ; SHARP Collaborative Group. Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection. BMC Nephrol. 2017 May 1;18(1):147. doi: 10.1186/s12882-017-0545-2.
Derived from this study: PubMed 28028192Herrington W, Staplin N, Judge PK, Mafham M, Emberson J, Haynes R, Wheeler DC, Walker R, Tomson C, Agodoa L, Wiecek A, Lewington S, Reith CA, Landray MJ, Baigent C; SHARP Collaborative Group. Evidence for Reverse Causality in the Association Between Blood Pressure and Cardiovascular Risk in Patients With Chronic Kidney Disease. Hypertension. 2017 Feb;69(2):314-322. doi: 10.1161/HYPERTENSIONAHA.116.08386. Epub 2016 Dec 27.
Derived from this study: PubMed 26385817Morton RL, Schlackow I, Staplin N, Gray A, Cass A, Haynes R, Emberson J, Herrington W, Landray MJ, Baigent C, Mihaylova B; SHARP Collaborative Group. Impact of Educational Attainment on Health Outcomes in Moderate to Severe CKD. Am J Kidney Dis. 2016 Jan;67(1):31-9. doi: 10.1053/j.ajkd.2015.07.021. Epub 2015 Sep 16.
Derived from this study: PubMed 18765432Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R. Analyses of cancer data from three ezetimibe trials. N Engl J Med. 2008 Sep 25;359(13):1357-66. doi: 10.1056/NEJMsa0806603. Epub 2008 Sep 2.
SHARP homepageLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Colin Baigent, FRCP, FFPH principal investigator

Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford

Martin J Landray, PhD, FRCP principal investigator

Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Simvastatin 20 mg and Ezetimibe 10mg in people with Kidney Disease, Chronic, run by University of Oxford at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Feb 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Key Outcome as Per Statistical Analysis Plan = Major Atherosclerotic Events Among All Patients Ever Randomized to Simvastatin Plus Ezetimibe Versus All Patients Allocated to Placebo (time frame: Median follow-up 4.9 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00125593, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2012.