European Cooperative Acute Stroke Study-4: Extending the time for thrombolysis in emergency neurological deficits

INTERVENTION: Patients will be randomized on a 1:1 basis to either receive Alteplase (0.9 mg/kg bw, not more than 90 mg) or placebo. Route of intervention: Intravenous (iv.) Duration: 1 hour Follow‐up: 3 months CONDITION: Stroke ; Circulatory System PRIMARY OUTCOME: Categorical shift in the modified Rankin Scale (mRS) at day 90 SECONDARY OUTCOME: 1. Disability at day 90, dichotomized as a favorable outcome (mRS) 0‐1 vs 2 ‐ 6 ; 2. Change in at least 11 National Institute of Health Stroke Scale (NIHSS) points or reaching 0 or 1 on this scale at day 1 and day 90 ; 3. Reperfusion at 12‐24 hours after treatment ; 4. Recanalization at 12‐24 hours after treatment ; 5. Infarct growth on diffusion‐weighted imaging (DWI) within 12‐24 hours after treatment ; 6. NIHSS score at day 7 ; 7. Barthel Index (BI) at day 90 ; 8. Montreal Cognitive Assessment (MoCA) score at day 90 INCLUSION CRITERIA: 1. Patients presenting with acute ischemic stroke 2. Patient or legally acceptable representative has given written informed consent. An independent witness may sign the consent form if the patient is able to give verbal consent but unable to sign 3. Patients, male and female, aged 18 years or over 4. Treatment onset within 4.5 and 9 hours after stroke onset or patients waking up with stroke symptoms and unclear time window 5. National Institutes of Health Stroke Scale (NIHSS) score of 4 to 26 with clinical signs of hemispheric infarction 6. Penumbral mismatch imaging via local assessment following predefined criteria using standardized criteria including a perfusion volume (PWI) to infarct core (DWI) ratio of = 1.2, and a minimum perfusion lesion volume of 20 ml