E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute ischaemic stroke refers to strokes caused by thrombosis or embolism and accounts for 85% of all strokes. |
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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 | 10023027 |
E.1.2 | Term | Ischaemic stroke NOS |
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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 investigate the safety and efficacy of treatment with intravenous recombinant tissue plasminogen activator (rt-PA) within 6 hours of onset of acute ischaemic stroke. |
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E.2.2 | Secondary objectives of the trial |
These will include exploration of the interaction between stroke severity, brain imaging appearances and time from onset of symptoms, to identify those patients who have the most the gain (or lose) from thrombolytic treatment; examination of the risks of intracranial haemorrhage identified by repeat brain imaging; and longer-term outcome to provide reliable estimates on the cost-effectiveness of trial treatment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Symptoms and signs of clinically definite acute stroke. •Time of stroke onset is known and treatment can be started within six hours of this onset. •CT or MRI brain scanning has reliably excluded both intracranial haemorrhage and structural brain lesions which can mimic stroke (e.g cerebral tumour).
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E.4 | Principal exclusion criteria |
•The patient has previously been randomised in IST-3 •Major surgery, trauma (e.g. major fall at time of stroke) or gastrointestinal or urinary tract haemorrhage within the previous 21 days. Arterial puncture at a non-compressible site within the previous 7 days. •Any known defect in coagulation (e.g. currently on oral anticoagulants with an INR > 1.3 OR current treatment with heparin [unless APPT within normal laboratory limits] OR treatment with low molecular weight heparin or heparinoid OR treatment with ximelagatran). •Known defect of clotting or platelet function (but patients on antiplatelet agents can be randomised). •The patient is female and of childbearing potential (unless it is certain that pregnancy is not possible) or breast feeding. •Hypo- or hyperglycaemia sufficient to account for the neurological symptoms; the patient should be excluded if their blood glucose is < 3.0 or > 20.0 mmol/L ('stick testing' is a sufficiently accurate test for this purpose). •Symptoms considered likely to resolve completely within the next few hours (i.e. a TIA) •Patient has had a stroke within the previous 14 days or has had treatment for acute ischaemic stroke with thrombolytic therapy within the past 14 days. •Patient was already dependent in activities of daily living before the present acute stroke •Patient has other life threatening illness (e.g. advanced cancer) likely to lead to death within a few months. •Likely to be unavailable for follow-up e.g. no fixed home address. •Patient has Blood Pressure < 90 mm Hg or > 220 mm Hg or Diastolic Blood Pressure < 40 mm Hg or > 130 mm Hg
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients alive and independent at 6 months |
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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 | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | 65 |
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 | 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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 12 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 12 |
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 |