E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10043647 |
E.1.2 | Term | Thrombotic 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 |
To collect efficacy and safety data on alteplase (rt-PA) in patients aged more than 80 years old, to demonstrate that the treatment of these patients within 3 hours of onset of symptoms of acute ischemic stroke with rt PA compared to patients receiving standard treatment, will result in an improved clinical outcome with a favourable benefit/risk ratio |
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E.2.2 | Secondary objectives of the trial |
- Study efficacy measures along 90 days; - Study prognostic factors; - Set, in this patient population, a neurological severity cut-off point, if any, below which, benefit/risk ratio of thrombolityc therapy is advantageous |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Female or male inpatients - Age > 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 haemorrhage. - Onset of symptoms < 3 hours 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 distinguishable from 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 deferred where applicable, according to the regulatory and legal requirements of the participating centres |
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E.4 | Principal exclusion criteria |
- Evidence of intracranial haemorrhage on the CT-scan. - Symptoms of ischemic attack began more than 3 hours 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>17) 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. - Prior stroke within the last 3 months - Patients with any history of prior stroke and concomitant diabetes - 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 below these limits. - Blood glucose <50 or > 200 mg/dl; values up to 300 mg/dl are allowed, if they can be reduced to < 200 mg/dl before treatment. - Known haemorrhagic diathesis - Patients receiving oral anticoagulants, e.g. warfarin sodium - Manifest or recent severe or dangerous bleeding - Known history of diagnosed or suspected intracranial haemorrhage - Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery) - History of Haemorrhagic retinopathy - Recent (less than 10 days) traumatic external heart massage - Recent (less than 10 days) puncture of a non-compressible blood-vessel (e.g. subclavian or jugular vein puncture). - Known current bacterial endocarditis, pericarditis. - Acute pancreatitis - Documented ulcerative gastrointestinal disease during the last 3 months - Documented oesophageal varices - Documented arterial- aneurysm, arterial/venous malformation - Neoplasm with increased bleeding risk - Severe liver disease, including hepatic failure, cirrhosis, portal hypertension - 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) |
Patients (%) with favourable outcome at day 90, according to: modified Rankin Scale (mRS) 0-2 |
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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 | Information not present in EudraCT |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
STANDARD TREATMENT ACCORDING TO NATIONAL GUIDELINES |
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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 | 46 |
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 | No |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |