E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary aim of SHARP is to assess the effects of lowering LDL-cholesterol with combined simvastatin 20 mg and ezetimibe 10 mg daily (denoted "ezetimibe/simvastatin") versus placebo on the time to a first “major vascular event”. A "major vascular event" is defined as: • non-fatal myocardial infarction (MI) or cardiac death; • non-fatal or fatal stroke; or • revascularisation, including coronary or non-coronary angioplasty or grafting, and non-traumatic amputation (but excluding vascular access surgery for dialysis).
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E.2.2 | Secondary objectives of the trial |
Secondary aims of the study include an assessment of the effects of ezetimibe/simvastatin on: progression to end-stage renal disease (among pre-dialysis patients); various causes of death; major cardiac events (defined as non-fatal MI or cardiac death); stroke; and hospitalisation for angina. The effects on major vascular events will also be examined among particular subgroups of patients.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• 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 (haemodialysis or peritoneal dialysis) • Men or women aged greater than or equal to 40 years
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E.4 | Principal exclusion criteria |
• Definite history of myocardial infarction or coronary revascularisation procedure • Functioning renal transplant, or living donor-related transplant planned • Less than 2 months since presentation as an acute uraemic emergency (but may be entered later, if appropriate); • 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); • Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or creatine kinase (CK) >3 x ULN; • Definite previous adverse reaction to a statin or to ezetimibe • 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: -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 is not using a reliable method of contraception.) • Known to be poorly compliant with clinic visits or prescribed medication • 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)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary aim of SHARP is to assess the effects of lowering LDL-cholesterol with combined simvastatin 20 mg and ezetimibe 10 mg daily(denoted "ezetimibe/simvastatin") versus placebo on the time to a first “major vascular event”. A "major vascular event" is defined as: • non-fatal myocardial infarction or cardiac death; • non-fatal or fatal stroke; or • revascularisation, including coronary or non-coronary angioplasty or grafting, and non-traumatic amputation (but excluding vascular access surgery for dialysis).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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SHARP is scheduled to continue until all patients have been followed for at least 4 years and at least 1100 major vascular events have occurred. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |