E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
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 |
Evaluate safety and tolerability of Glivec (Imatinib) for use in acute stroke patients undergoing intravenous thrombolysis |
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E.2.2 | Secondary objectives of the trial |
Evaluate effect on haemorrhagic transformation and oedema of cerebral infarcts following iv thrombolysis with and without treatment with Imatinib, evaluate neurological and functional outcome |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Clinical diagnosis of ischaemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition, gaze, vision and/or neglect. Ischaemic stroke is defined as an event characterised by sudden onset of acute focal neurological deficit, presumed to be caused by cerebral ischaemia, after CT scan exclusion of haemorrhage
- Neurological deficit is corresponding to 7 points or higher on the National Institutes of Health Stroke Scale (NIHSS)
- Age 18 – 85 years
- Symptoms must be distinguishable from an episode of generalised ischaemia (i.e. syncope), seizure, or migraine disorder
- Intravenous thrombolysis is indicated on clinical grounds and has been initiated within 4.5 hours of stroke onset
- Patients can be randomised to active treatment or control as soon as possible but at least within one hour after completion of intravenous thrombolysis, or if applicable, after completion of additional intraarterial intervention
- Patients has provided informed consent with regard to participation in the study, retrieval and storage of data and follow up procedures
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E.4 | Principal exclusion criteria |
- Evidence of intracranial haemorrhage (including haemorrhagic transformation or intracerebral haemorrhage) on the baseline CT-scan
- Severe stroke as assessed clinically (e.g. NIHSS>25) and/or developing infarct extending into more than 1/3 of the Middle Cerebral Artery territory or ½ of other vascular territories
- Administration of heparin within the previous 48 hours preceding the onset of stroke with an elevated activated thromboplastin time (aPTT) at presentation, or corresponding low-molecular heparin.
- Platelet count of below 100,000/mm3.
- Significant bleeding disorder at present or within the past 6 months, known haemorrhagic diathesis
- Patients receiving oral anticoagulants, e.g. warfarin sodium (INR>1.3)
- History or evidence or suspicion of intracranial haemorrhage including sub-arachnoid haemorrhage
- Severe uncontrolled arterial hypertension
- 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) or other haemorrhagic ophthalmic conditions
- Acute pancreatitis
- Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis
- Ongoing treatment with chemotherapy
- Drugs which may increase the plasma concentration of imatinib - ketokonazol, itrakonazol, erythromycin and claritomycin
- Drugs which may decrease the plasma concentration of Imatinib: Dexametason, phenytoin, karbamazepin, rifampizin, phenobarbital, fosphenytoin, primidon, Hypericum performatum (Johannesört)
- Major surgery or significant trauma in past 10 days (this includes any trauma associated with current acute myocardial infarction), recent trauma to head or cranium
- Pregnancy not excluded if patient is in childbearing potential
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E.5 End points |
E.5.1 | Primary end point(s) |
• Serious and non-serious adverse events (in particular listed as reported adverse events in long-term treatment for oncological indications) • Mortality • Laboratory values, in particular blood cell count, bilirubin, ASAT, ALAT, amylase and creatinin.
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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 | Yes |
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 | 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 |
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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 | 4 |
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 | No |
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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Plan of three levels, each of 20 patients Level I, 400 mg daily vs control (no treatment): 15 patients active, 5 control if cleased by safety committee Level II, 600 mg daily vs control (no treatment): 15 patients active, 5 control if cleared by safety committee Level III, 800 mg daily vs control (no treatment): 15 patients active, 5 control |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |