E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary prevention of atherothrombotic cardiovascular disease |
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E.1.1.1 | Medical condition in easily understood language |
narrowing of the blood vessels |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051615 |
E.1.2 | Term | Atherosclerotic cardiovascular disease |
E.1.2 | System Organ Class | 100000004866 |
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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 principal aims of the study are: 1) To find out whether, in a wide range of middle aged or older people at moderate risk of cardiovascular disease, with average levels of cholesterol and blood pressure, 5 to 7 years of treatment with drugs to lower cholesterol, blood pressure or both, can reduce the risk of dying from cardiovascular disease or having a heart attack or stroke. 2) To find out whether lowering cholesterol, blood pressure or both in the study population, result in a reduction in the incidence of death from any cause, and of a composite outcome including death from cardiovascular causes, nonfatal heart attack, nonfatal stroke, resuscitated cardiac arrest, and coronary revascularisation with evidence of ischaemia or heart failure. Additional aims are to assess whether the study treatments affect the incidence or progression of kidney disease, the need for arterial revascularisation (of the heart, brain or limbs), the occurrence of newly diagnosed diabetes, cognitive fu |
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E.2.2 | Secondary objectives of the trial |
Secondary aims are to find out whether lowering cholesterol, blood pressure or both in the study population, result in a reduction in the incidence of death from any cause. Components of the primary outcomes. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Women aged ≥60 years with at least two additional risk factors and, women aged >65 years and men ≥55 years with at least one additional risk factor
• Suggested cardiovascular risk factors for trial eligibility: o Waist/hip ratio ≥0.90 in men and ≥0.85 in women o History of current or recent smoking (regular tobacco use within 5 years) o Low HDL cholesterol (for example, HDL cholesterol <1.0 mmol/L [40 mg/dl] in men and <1.3 mmol/L [50 mg/dl] in women) o Dysglycaemia (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] or uncomplicated diabetes treated by diet only) o Renal dysfunction - microalbuminuria - estimated GFR <60 ml/min/1.73 m2 or creatinine >124 μmol/L (1.4 mg/dL) (unless the participant has proteinuria or blood pressure >130/80 mmHg) o Family history of premature coronary heart disease or stroke in first-degree relatives (age <55 years in men or <65 years in women)
• Provision of informed consent |
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E.4 | Principal exclusion criteria |
• Documented clinically manifest atherothrombotic cardiovascular disease
• Clear indication for statin and/or ARB, or ACE inhibitor and/or thiazide diuretic therapy, as determined by the subject’s own local physician
• Clear contraindication for statin and/or ARB and/or thiazide diuretic therapy, as determined by the subject’s own local physician*
• Concurrent treatment with a statin or a fibrate (subjects on cholesterol-lowering diets or drugs other than statins or fibrates can still be included)
• Concurrent treatment with an angiotensin receptor blocker, ACE inhibitor, Direct Renin Inhibitor or a thiazide diuretic
• Symptomatic hypotension
• Chronic liver disease (i.e. cirrhosis or persistent hepatitis) or abnormal liver function, i.e. ALT or AST >3 x upper limit of normal [ULN]
• Inflammatory muscle disease (such as dermatomyositis or polymyositis) or creatine kinase (CK) >3 x ULN
* Subjects with persistently elevated blood pressure and who are considered by the local physician to require antihypertensive therapy can be entered in the trial after blood pressure control is attained with lifestyle interventions or with drugs other than an ARB, an ACE inhibitor, a Direct Renin Inhibitor or a thiazide diuretic. Subjects on lipid lowering therapy other than a statin or a fibrate can be entered in the trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) A composite of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. 2) The composite of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, heart failure or arterial revascularizations.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Blood samples to assess genetic markers of prognosis |
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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 | Yes |
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) | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 | No |
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 | Yes |
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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The trial has two phases. The first 'active' phase (during which participants receive the study drugs) will last for a maximum of seven years and the subsequent 'inactive' phase will comprise annual follow up for at least 10 years, during which participants will be contacted every year to identify major cardiovascular events. The end of trial is defined as the completion of data entry following the last visit of the last subject. |
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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 | 15 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 18 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 31 |