E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 |
The primary hypothesis of this study is that the percentage of patients with good clinical outcome after 3 months (mRS 0-2) is increased compared to patients treated with standard IVT (as documented within the Austrian Stroke Unit registry) when adjusted for relevant outcome parameters (age, stroke severity, vascular territory, diabetes and onset to treatment time). |
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E.2.2 | Secondary objectives of the trial |
• mortality after 3 months compared to matched patients treated with standard IVT (as documented within the Austrian Stroke Unit registry) • symptomatic intracranial hemorrhage (according to NINDS and SITS MOST/dB3 criteria) compared to matched patients treated with standard IVT (as documented within the Austrian Stroke Unit registry) • excellent clinical outcome after 3 months as measured by a modified Rankin Scale of 0-1 • causes of mortality after 3 months • percentage of patients with rapid improvement (> 4 points of the NIHSS) within the first 24 hours • Complete or partial recanalisation (TIMI 2 or 3) at the end of endovascular therapy, time to recanalisation; association between time to recanalisation and probability of good clinical outcome (mRS 0-2) after 3 months
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age between 18 – 80 years • Clinical syndrome of a severe ischemic lesion within the anterior circulation („Total Anterior Circulation Syndrome“ TACS) or of basilar artery occlusion • NIHSS > 12 • Start of IVT within 3 hours („bridging“, „rescue“) or within 4.5 hours (`primary endovascular management`) • Confirmation of proximal occlusion • Absence of exclusion criteria
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E.4 | Principal exclusion criteria |
• History of stroke within the last 3 months • History of subarachnoid or intracranial hemorrhage, known cerebrovascular arteriovenous malformation or CNS tumour • Clinical suggestion of subarachnoid hemorrhage and negative CT • Uncontrolled systolic blood pressure • Evidence of septic embolism etiologically related to stroke • Evidence of pericarditis including pericarditis after myocardial infarction • Operation or biopsy of a body organ within the last 30 days (not an exclusion criterion for primary endovascular treatment) • Trauma with inner or outer ulcerous wounds within the last 30 days (not an exclusion criterion for primary endovascular treatment) • Severe head trauma or concussion within the last 90 days • Current bleeding • Systemic bleeding (outside the head) within the last 30 days (not an exclusion criterion for primary endovascular treatment) • Known hereditary or acquired hemorrhagic diathesis , known hereditary or acquired coagulation factor deficiency; oral anticoagulation and a prolonged prothrombin time (INR > 1.5) • Women of childbearing age with known pregnancy or positive pregnancy test • Baseline platelet count < 100,000/mm or haematocrit < 25% • Patients on treatment with unfractioned heparin within the last 48 hours and prolonged partial thromboplastin time exceeding the upper limit of the local laboratory normal range • Arterial puncture at a non-compressible site or spinal tab within the past 7 days (not an exclusion criterion for primary endovascular treatment) • Uncertainty if neurological deficit is caused by vessel occlusion, e.g. after an epileptic seizure or neurologic/psychiatric illness • Known severe progressive or terminal illness • Any other reason that, in the opinion of the investigator, would bear a risk for rt-PA treatment
Imaging exclusion criteria: CT-criteria: • any hemorrhage • edema with mass effect and midline shift • extensive hypodensity (> 1/3 of MCA territory) MR-criteria: • Extensive diffusion lesion (> 1/3 of MCA territory) • No mismatch (at the discretion of treating neurologists/radiologists)
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E.5 End points |
E.5.1 | Primary end point(s) |
Modified Rankin Scale Score 0-2 after 3 months |
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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) |
Mortality after 3 months Incidence of symptomatic intracranial hemorrhage
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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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | 10 |
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 | 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 | 3 |
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 | 3 |