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| ID | Type | Description | Link |
|---|---|---|---|
| ISRCTN54137607 | Other Identifier | ISRCTN (Current Controlled Trials) | |
| EudraCT - 2004-001156-37 | Other Identifier | European Union | |
| UK CRN 2542 | Other Identifier | United Kingdom Clinical Research Network |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
| Schering-Plough | INDUSTRY |
| National Health and Medical Research Council, Australia | OTHER |
| British Heart Foundation |
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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). It also aimed to assess whether lowering LDL cholesterol reduced the rate of loss of renal function in people with CKD who had not commenced dialysis treatment.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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). |
|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Simvastatin 20 mg | Drug | Once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Median follow-up 4.9 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Median follow-up 4.9 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Colin Baigent, FRCP, FFPH | Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford | Principal Investigator |
| Martin J Landray, PhD, FRCP | Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford | Oxford | OX3 7LF | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15754269 | Background | 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. | |
| 16490616 |
| Label | URL |
|---|---|
| SHARP homepage | View source |
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Run-in period between screening and randomization of ~ 6 weeks duration. 11792 patients screened and 9438 randomized to the initial 3 arms. Overall 9270 patients were randomly assigned to simvastatin plus ezetimibe (4650 patients, 4193 initially plus 457 after first year) versus placebo (4620 patients, 4191 initially plus 429 after first year).
SHARP was conducted in 380 centres in 18 countries: Austria, Australia, Canada, China, The Czech Republic, Denmark, Finland, France, Germany, Malaysia, The Netherlands, New Zealand, Norway, Poland, Sweden, Thailand, the United Kingdom and the United States of America. Recruitment occurred between 2003 and 2006.
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| ID | Title | Description |
|---|---|---|
| FG000 | Simvastatin 20mg Plus Ezetimibe 10mg | A double-dummy method ensured that patients and study staff were unaware of the treatment allocation, with all patients taking 2 tablets during the first year (active simvastatin plus ezetimibe tablet with a placebo simvastatin tablet). After the first year, all patients took one tablet (active simvastatin 20mg plus ezetimibe 10mg tablet). |
| FG001 | Placebo | A double-dummy method ensured that patients and study staff were unaware of the treatment allocation, with all patients taking 2 tablets (placebo simvastatin plus ezetimibe tablet with a placebo simvastatin tablet) during the first year. After the first year, all patients took one tablet (placebo simvastatin plus ezetimibe tablet). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Simvastatin Plus Ezetimibe | Once daily tablet |
| BG001 | Placebo | Once daily tablet |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Number | participants | Median follow-up 4.9 years |
|
Median follow-up 4.9 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Simvastatin Plus Ezetimibe | Once daily tablet |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vascular death | Vascular disorders | Custom vocabulary | Systematic Assessment | Note that the sum total of vascular deaths, non-vascular deaths and unknown causes of death equates to all cause mortality |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Muscle pain | Musculoskeletal and connective tissue disorders | Custom vocabulary | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Colin Baigent | Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford | +44 1865 743743 | colin.baigent@ctsu.ox.ac.uk |
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| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D002318 | Cardiovascular Diseases |
| D050197 | Atherosclerosis |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D019821 | Simvastatin |
| D000069438 | Ezetimibe |
| D000069499 | Ezetimibe, Simvastatin Drug Combination |
| ID | Term |
|---|---|
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| OTHER |
| Medical Research Council | OTHER_GOV |
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| Ezetimibe 10mg | Drug | Once daily |
|
|
| Placebo | Drug | Once daily |
|
| 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. | 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. | 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. | 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. | 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. | Median follow-up 4.9 years |
| Background |
| 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. |
| 21095263 | Background | 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. |
| 21663949 | Result | 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. |
| 38018702 | Derived | 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. |
| 31662874 | Derived | 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. |
| 31005271 | Derived | 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. |
| 28780579 | Derived | 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. |
| 28460629 | Derived | 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. |
| 28028192 | Derived | 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. |
| 26385817 | Derived | 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. |
| 18765432 | Derived | 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. |
| BG002 |
| Total |
Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Renal status | Number | Participants |
|
| OG001 |
| Placebo |
A double-dummy method ensured that patients and study staff were unaware of the treatment allocation, with all patients taking 2 tablets (placebo simvastatin plus ezetimibe tablet with a placebo simvastatin tablet) during the first year. After the first year, all patients took one tablet (placebo simvastatin plus ezetimibe tablet). |
|
|
|
| Secondary | 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. | Posted | Number | participants | Median follow-up 4.9 years |
|
|
|
|
| Secondary | 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. | Includes only those patients initially randomized to simvastatin plus ezetimibe versus placebo (as opposed to all patients ever randomized to simvastatin plus ezetimibe versus all patients allocated placebo) | Posted | Number | participants | Median follow-up 4.9 years |
|
|
|
|
| Secondary | 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. | Posted | Number | participants | Median follow-up 4.9 years |
|
|
|
|
| Secondary | 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. | Posted | Number | participants | Median follow-up 4.9 years |
|
|
|
|
| Secondary | 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. | Posted | Number | participants | Median follow-up 4.9 years |
|
|
|
|
| Secondary | 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. | Posted | Number | participants | Median follow-up 4.9 years |
|
|
|
|
| 1,142 |
| 4,650 |
| 992 |
| 4,650 |
| EG001 | Placebo | Once daily tablet | 1,115 | 4,620 | 960 | 4,620 |
|
| Non-vascular deaths | General disorders | Custom vocabulary | Systematic Assessment | Note that the sum total of vascular deaths, non-vascular deaths and unknown causes of death equates to all cause mortality |
|
| Unknown causes of death | General disorders | Custom vocabulary | Systematic Assessment | Note that the sum total of vascular deaths, non-vascular deaths and unknown causes of death equates to all cause mortality |
|
Not provided
Not provided
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| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D001384 | Azetidines |
| D001385 | Azetines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |