E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute ischemic stroke in the A. cerebri media territory |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055221 |
E.1.2 | Term | Ischemic stroke |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061256 |
E.1.2 | Term | Ischaemic stroke |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027580 |
E.1.2 | Term | Middle cerebral artery stroke |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061256 |
E.1.2 | Term | Ischaemic stroke |
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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 main objective of this trial is to assess the efficacy and safety of propranolol in middle cerebral artery stroke patients.
The primary hypothesis is as follows
Early administration of propranolol reduces the frequency of cardiovascular and/or neurological complications including vascular death in the first 30 days after acute ischemic stroke. |
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E.2.2 | Secondary objectives of the trial |
Secondary hypotheses are as follows:
Early administration of propranolol improves neurological and functional outcome of patients with acute ischemic stroke.
Early administration of propranolol reduces post-stroke immunodepression and therefore lowers the rate of pneumonia after acute ischemic stroke, without increasing the frequency of auto-aggressive, CNS antigen-specific T cells.
Early administration of Propranolol influences alterations in cardiologic, electrophysiologic phenomenons as a reaction to autonomic dysregulation after acute ischemic stroke.
Early administration of Propranolol reduces growth of infarct as determined by MRI examinations in the first 6 days. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Age ≥ 18 2) Clinical syndrome of an acute ischemic middle cerebral artery stroke with a) an NIHSS score ≥ 4 and compatible imaging or b) proof of non-lacunar MCA-infarction with an adequate imaging technique 3) Treatment has to start within 18 h after symptom onset 5) For premenopausal women: negative result of a pregnancy test and highly effective contraception (defined with a Pearl Index <1) 6) Informed Consent by patient
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E.4 | Principal exclusion criteria |
1) Patient is enrolled in another interventional trial. 2) Every severe or fatal disease, that reduces the life expectancy to less than 1 year, except the ischemic stroke. 3) Any contraindication to the administration of propranolol. 4) Clinically relevant interactions of propranolol with the necessary, administered medication prescribed by the treating physician. 5) Patient is already being treated with beta-blockers. 6) Patient is or was recently undergoing antiarrhythmic, immunosuppressive or antiinfective treatment. 7) Myocardial infarction during the last 3 months. 8) Heart rate > 110 bpm 9) any unstable or severe heart disease (i.e. heart failure NYHA III-IV) 10) severe chronic arterial hypertension 11) Patient is suffering from acute, uncontrolled hypotension at the time of screening. 12) Patient is suffering form a serious liver disease. 13) Alcohol or drug abuse. 14) Pregnancy or nursing period 15) The patient or his legal representative is not giving consent to the saving, archiving and forwarding of pseudonymic data. 16) Clinical or laboratory signs of infection warranting treatment. 17) Any other condition that could to the discretion of the Investigator impose hazards to the patient if study therapy was initiated. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint is the incidence of cardiovascular and/or neurological complications including vascular death within the first 30 days after acute ischemic stroke.
These include: 1) Excessive hypertension, defined by the necessity of a new or second antihypertensive or a higher dosage. 2) Non-fatal episode of cardiovascular complications (as atrial fibrillation, ventricular tachycardia, ventricular fibrillation, myocardial infarction, clinically relevant deterioration of or newly diagnosed heart failure) 3) Non-fatal episode of neurological complications (as recurrent stroke, intraparenchymal haemorrhage, intracranial hypertension) 4) Vascular death - defined as death through one of the above mentioned complications |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
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 trial is defined by the last visit of the last patient included. The screening period lasts 3 years, patients are being followed up for 3 months, therefore the duration of trial will be approximately 3 years and 3 months. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |