E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute ischaemic stroke upon awakening ("wake-up stroke") |
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E.1.1.1 | Medical condition in easily understood language |
Stroke that occurs during sleep |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 answer the following question: - Can thrombolytic treatment with tenecteplase given within 4.5 hours of wake-up reduce the risk of poor functional outcome at 3 months?
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E.2.2 | Secondary objectives of the trial |
To answer the following question: - Can findings on plain CT and CT angiography (and CT perfusion at selected centres) identify patients who benefit from such treatment, compared to patients without such findings?
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Value of multi-modal CT for selection of patients with wake-up stroke for thrombolytic treatment (Protocol version/date 160204).
This sub-study covers the second objective (paragraph E.2.2, above). |
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E.3 | Principal inclusion criteria |
• Stroke symptoms on awakening that were not present before sleep • Clinical diagnosis of stroke with limb weakness with NIHSS score >5, or dysphasia. • Treatment with tenecteplase is possible within 4.5 hours of awakening • Written consent from the patient, non-written consent from the patient (witnessed by non-participating health care personnel), or written consent from the nearest family member. |
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E.4 | Principal exclusion criteria |
• Age < 18 years • Findings on plain CT that indicate that the patient is unlikely to benifit from treatment: - Infarction comprising more than >1/3 of the middle cerebral artery territory on plain CT - Intracranial haemorrhage, structural brain lesions which can mimic stroke (e.g cerebral tumour) • Patient will be treated with intra-arterial interventions for proximal cerebral artery occlusion • High risk of bleeding, e.g.: - Major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days. - Any known defect in coagulation, e.g. current use of vitamin K antagonist with an INR > 1.7, or other oral anticoagulant, or heparins - Known defect of clotting or platelet function (but patients on antiplatelet agents can be included) - Ischaemic stroke in previous 2 weeks, previous intracranial haemorrhage, or known arteriovenous malformation or aneurysm • Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg), despite blood pressure lowering treatment • Blood glucose < 3.0 or > 20.0 mmol/L • Childbearing potential, pregnancy, positive pregnancy test, breastfeeding • Other serious or life-threatening disease before the stroke: severe mental or physical disability (e.g. Mini Mental Status score < 20, or modified Rankin Scale score ≥ 3), or life expectancy less than 12 months • Patient unavailability for follow-up (e.g. no fixed address) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Functional outcome (defined by the modified Rankin Scale) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Clinical events: • Intracranial haemorrhage during the first 7 days • Stroke progression during the first 7 days • Recurrent ischaemic stroke during the first 7 days • Death from all cause during the first 7 days and during 3 months’ follow-up
Clinical outcomes: Barthel Index score, EuroQol score, and MMSE scores at 3 months.
Health-economic variables: Costs related to length of hospital stay, care in nursing home etc., re-hospitalisations during first 3 months |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.5 | Efficacy | No |
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 | 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 |
Best standard care alone (without tenecteplase) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |