E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute stroke (ischemic or haemoragic) |
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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 |
Is AT1 receptor blockade with candesartan in acute stroke effective in: 1. reducing the risk of death or major disability at 6 months? 2. preventing vascular death, myocardial infarction, or stroke during the first 6 months?
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E.2.2 | Secondary objectives of the trial |
Clinical outcomes: • Scandinavian Stroke Scale score at 7 days and 6 months • Modified Rankin scale score at 1, 3, and 6 months • Barthel Index score at 1, 3, and 6 months • EuroQol score at 6 months • Mini-Mental State score at 3 and 6 months
Clinical events During the 6 months’ follow-up period: • Death (all-cause death and “vascular” death) • Recurrent stroke (ischaemic, haemorrhagic, or unspecified) • Myocardial infarction • Combination of the above events • Adverse events (symptomatic hypotension, renal failure, etc.)
Health-economic measures: Costs related to: • Length of hospital stay • Discharge disposition • Re-hospitalisations during the first 6 months
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Clinical stroke syndrome with limb paresis, not likely to represent a transient ischaemic attack or non-stroke pathology (e.g. cerebral tumour) 2. Systolic blood pressure ≥ 140 mm Hg (see paragraph 7.1 for details) 3. Trial treatment possible within 30 hrs of symptom onset. If time of onset is not known, use the time when the patient was last known to be well. 4. Consent (subsidiary, assent from legal acceptable representative, or waiver of consent, see paragraph 7.2 in protocol for details) 5. Age >18 years |
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E.4 | Principal exclusion criteria |
1. Markedly reduced consciousness (e.g. Scandinavian Stroke Scale consciousness score ≤ 2) 2. Patient already receiving AT1 receptor blocker 3. Contraindication to treatment with AT1 receptor blocker, e.g.: • known renal failure (women: creatinine ≥ 150 µmol/L; men: ≥ 180 µmol/L) • previously diagnosed bilateral renal artery stenosis • previously diagnosed high-grade aortic stenosis • previously diagnosed seriously impaired liver function and/or cholestasis • known intolerance to candesartan or other tablet ingredients 4. Clear indication, in the clinician’s view, for start of treatment with AT1 receptor blocker during the treatment period 5. Clear indication, in the clinician’s view, for antihypertensive therapy during the acute phase of stroke (i.e. concurrent hypertensive encephalopathy or aortic dissection, or other situations) 6. Other serious or life-threatening disease before the stroke: • patient severely mentally or physically disabled (e.g. Mini Mental Status score < 15-20, or modified Rankin Scale score ≥ 4) • life expectancy < 12 months 7. Patient unavailable for follow-up (e.g. no fixed address) 8. Pregnant or breast-feeding woman
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E.5 End points |
E.5.1 | Primary end point(s) |
Hypothesis: AT1 receptor blockade with candesartan in acute stroke will: 1. reduce the risk of death or major disability at 6 months by 6% relative to placebo. 2. reduce the risk of death, myocardial infarction, or stroke by 25% during the first 6 months, relative to placebo.
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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 | Yes |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | 30 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 200 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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End of study is defined as Data Base Lock, which is the timepoint after which no subject will be exposed to study related activities and all data about each patient have been finally checked. |
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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 | 3 |
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 | 3 |