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

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 264

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

Exclusion Criteria

1. Intracranial hemorrhage (ICH) identified by CT or MRI
2. Rapidly improving symptoms, particularly if, in the opinion of the investigator, the improvement is likely to result in the patient having an NIHSS score of <4 at randomization
3. Pre-stroke modified Rankin Scale (mRS) score of >1 (indicating previous disability)
4. Contraindication to imaging with MRI
5. Infarct core >1/3 MCA territory qualitatively or >100 ml quantitatively (determined by DWI lesion on MRI)
6. Participation in any investigational study in the previous 30 days
7. A life expectancy of less than 3 months
8. Any condition that, in the opinion of the investigator, could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study (this applies to patients with severe microangiopathy such as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura)
9. Pregnant (clinically evident) or breastfeeding women
10. Previous stroke within the three months prior to randomization
11. Recent history (in the opinion of the investigator) or clinical presentation of ICH, subarachnoid hemorrhage (SAH), arterio-venous (AV) malformation, aneurysm or cerebral neoplasm
12. Current use of oral anticoagulants and a prolonged prothrombin time (INR > 1.6) or any activated partial thromboplastin (aPTT) time exceeding 1.5-times the normal range or prolonged Thrombin-Time (TT), indicating the potential use of Dabigatran-Etexilate
13. Use of heparin, except for low-dose subcutaneous heparin, within 48 hours prior to randomization
14. Use of glycoprotein IIb-IIIa inhibitors within 72 hours prior to randomization
15. Clinically significant hypoglycemia
16. Uncontrolled hypertension defined by blood pressure > 185 mmHg systolic or >110 mmHg diastolic on at least two separate occasions at least 10 minutes apart, or requiring aggressive treatment to reduce the blood pressure to within these limits. The definition of aggressive treatment is left to the discretion of the investigator
17. Hereditary or acquired hemorrhagic diathesis
18. Gastrointestinal or urinary bleeding within 21 days prior to randomization
19. Major surgery within 14 days prior to randomization which poses a risk in the opinion of the investigator
20. Exposure to a thrombolytic agent within 72 hours prior to randomization

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Categorical shift in the modified Rankin Scale (mRS) at day 90

Secondary Outcome Measures

Name	Time	Method
<br> 1. Disability at day 90, dichotomized as a favorable outcome (mRS) 0-1 vs 2 - 6<br> 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<br> 3. Reperfusion at 12-24 hours after treatment<br> 4. Recanalization at 12-24 hours after treatment<br> 5. Infarct growth on diffusion-weighted imaging (DWI) within 12-24 hours after treatment<br> 6. NIHSS score at day 7<br> 7. Barthel Index (BI) at day 90<br> 8. Montreal Cognitive Assessment (MoCA) score at day 90<br>