E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute ischemic hemispheric stroke |
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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 collect additional confirmatory data on alteplase (rt-PA) in the European setting and to demonstrate that the treatment of patients between 3 and 4 hours 30 minutes of onset of symptoms of acute ischemic stroke with rt-PA compared to the placebo-treated patients will result in an improved clinical outcome without increase of fatality rate. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Female or male inpatients Age: 18 - 80 years. Clinical diagnosis of ischemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition and/or gaze, vision or neglect. Ischemic stroke is defined as an event characterized by the sudden onset of an acute focal neurologic deficit presumed to be due to cerebral ischemia after CT scan excludes hemorrhage. Onset of symptoms between 3 and 4 hours 30 minutes prior to initiation of administration of study drug. Stroke symptoms are to be present for at least 30 minutes and have not significantly improved before treatment. Symptoms must be distinguishablefrom an episode of generalized ischemia (i.e. syncope), seizure, or migraine disorder. Patient is willing to participate voluntarily and to sign a written patient informed consent. Informed consent will be obtained from each patient or the subject’s legally authorized representative or relatives, or defered where applicable, according to the regulatory and legal requirements of the participating country. Patients who are unable to sign but who are able to understand the meaning of participation in the study may give an oral witnessed informed consent. These patients have to make clear undoubtfully that they are willing to participate voluntarily and must be able to understand an explanation of the contents of the information sheet. Willingness and ability to comply with the protocol. |
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E.4 | Principal exclusion criteria |
Evidence of intracranial hemorrhage (ICH) on the CT-scan. Symptoms of ischaemic attack began more than 4 hours 30 minutes prior to infusion start or when time of symptom onset is unknown. Minor neurological deficit or symptoms rapidly improving before start of infusion. Severe stroke as assessed clinically (e.g. NIHSS>25) and/or by appropriate imaging techniques. Epileptic seizure at onset of stroke Symptoms suggestive of subarachnoid haemorrhage, even if the CT-scan is normal. Administration of heparin within the previous 48 hours and a thromboplastin time exceeding the upper limit of normal for laboratory Patients with any history of prior stroke and concomitant diabetes Prior stroke within the last 3 months Platelet count of below 100,000/mm3. Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, or aggressive management (IV medication) necessary to reduce BP to these limits. Blood glucose < 2.77 or > 22.15 mmol / l. Known haemorraghic diathesis Patients receiving oral anticoagulants, e.g. warfarin sodium Manifest or recent severe or dangerous bleeding Known history of or suspected intracranial haemorrhage Suspected subarachnoid haemorrhage or condition after subarachnoid haemorrhage from aneurysm Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery) Haemorrhagic retinopathy,e.g. in diabetes (vision disturbances may indicate haemorrhagic retinopathy) Recent (less than 10 days) traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood-vessel (e.g. subclavian or jugular vein puncture. Known bacterial endocarditis, pericarditis. Acute pancreatitis Documented ulcerative gastrointestinal disease during the last 3 months, oesophageal varices, arterial- aneurysm, arterial/venous malformation Neoplasm with increased bleeding risk Severe liver disease, including hepatic failure, cirrhosis, portal hypertension oesaphageal varices) and active hepatitis Major surgery or significant trauma in past 3 months. Current or recent (within 3 months) participation in another investigational drug treatment protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
mRS 0-1 (favourable outcome) at day 90 |
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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 | Information not present in EudraCT |
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.8.5 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |