E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy individuals at average risk, without a clear indication or contraindication to lipid lowering or blood pressure lowering with any of the study drugs. Women aged >65 and men aged >55, with one additonal CV risk factor (for details: see Protocol), are eligible in the absence of documented clinically manifest atherothrombotic CVD, or other major illness(es) expected to interfere with study paricipation. |
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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 |
To evaluate the effecs of lipid modification with rosuvastatin and blood pressure lowering with candesartan/hydrochlorothiazid and a combination of both in awide range of middle aged peaople, who are at average risk for vascular events.
(a) To evaluate the effects of lipid modification (LDL cholesterol lowering and HDL cholesterol raising) with rosuvastatin 10 mg daily on major CV events.
(b) To evaluate the effects of blood pressure lowering with combined candesartan 16 mg/HCT 12.5 mg daily on major CV events.
(c) To evaluate the impact of combined lipid modification with rosuvastatin 10 mg/day and blood pressure lowering with candesartan 16 mg/HCT 12.5 mg daily on major CV events.
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E.2.2 | Secondary objectives of the trial |
To evaluate the effects of rosuvastatin and of candesartan/hydrochlorothiazide and of their combination on: 1. Total mortality 2. CV mortality 3. Coronary heart disease events 4. Cerebrovascular disease events 5. Heart failure 6. Revascularization procedures 7. Angina pectoris 8. Progression of renal disease 9. New diagnosis of diabetes
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Women aged ³ 65 years and men ³ 55 years -One additional CV risk factor Suggested CV 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 Dysglycemia (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] or uncomplicated diabetes treated by diet only or at most one oral hypoglycaemic drug) o Renal dysfunction -Microalbuminuria -estimated GFR <60 ml/min or creatinine > 124 µmol/L (1.4 mg/dL) o Family history of premature CHD 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 CVD -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 or ACE inhibitor and/or thiazide diuretic therapy, as determined by the subject’s own local physician -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 -Severe renal impairment (calculated creatinine clearance [CrCl] <30 ml/min/1.73 m2 or serum creatinine > 264μmol/L (3.0 mg/dl) -Concurrent treatment with cyclosporine or a condition likely to result in organ transplantation and the need for cyclosporine -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, a thiazide diuretic. -Other serious medical illness likely to interfere with study participation or with the ability to complete the trial -Significant psychiatric illness, senility, dementia, alcohol or substance abuse, which could impair the ability to provide informed consent and to adhere to the trial procedures -Concurrent use of an experimental pharmacological agent
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E.5 End points |
E.5.1 | Primary end point(s) |
For the rosuvastatin vs. placebo arm of the trial the primary outcome is the composite of CV death, nonfatal myocardial infarction (MI), nonfatal ischemic stroke, resuscitated cardiac arrest and arterial revascularizations.
For the candesartan/HCT vs. placebo arm of the trial the primary outcome is the composite of CV death, nonfatal MI, nonfatal stroke, heart failure, resuscitated cardiac arrest and arterial revascularizations.
For the combined rosuvastatin plus candesartan/HCT vs. rosuvastatin placebo plus candesartan/HCT placebo comparison the primary outcome is the composite of CV death, nonfatal MI, nonfatal stroke, heart failure, resuscitated cardiac arrest and arterial revascularizations. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Blood samples for genetic markers of prognosis of CVD |
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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) | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | 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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Is provided in the protocol |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 1 |