Extending the time for thrombolytic treatment after stroke.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 264

Inclusion Criteria

- Patients presenting with acute ischemic Middle Cerebral Artery (MCA) stroke
- 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
- Patient’s age is =18 years
- Treatment onset within = 4.5 – 9 hours after stroke onset*
*Patients with 'wake up' strokes may be included. 'Wake up’ strokes are defined as having no stroke symptoms at sleep onset, but on waking. The time of stroke onset is to be taken as the mid-point between sleep onset (or last known to be normal) and time of waking.
- NIHSS score of 4 to 26 with clinical signs of hemispheric infarction
- Penumbral mismatch imaging via local assessment using a computer based analysis system (e.g. RAPID) if available, using a perfusion volume (PWI) to infarct core (DWI) ratio of = 1.2, and a minimum perfusion lesion volume of 20 ml.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 132
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 132

Exclusion Criteria

- Intracranial hemorrhage (ICH) identified by CT or MRI
- 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
- Pre-stroke mRS score of >1 (indicating previous disability)
- Contra indication to imaging with MRI
- Infarct core >1/3 MCA territory qualitatively or >100 ml quantitatively (determined by DWI lesion on MRI)
- Any MRI findings indicative of a high risk of ICH related to potential iv-rtPA treatment in the judgment of the investigator
- Participation in any investigational study in the previous 30 days
- A life expectancy of <3 months
- 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).
- Pregnant (clinically evident) or breastfeeding women
- Previous stroke within the three months prior to randomization
- Recent history (in the opinion of the investigator) or clinical presentation of ICH, subarachnoid hemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm.
- Use of oral anticoagulants within 48 hours prior to randomization (including, but not limited to Rivaroxaban, Apixaban, or Edoxaban) 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.
- Use of heparin, except for low dose subcutaneous heparin, within 48 hours prior to randomization
- Use of glycoprotein IIb-IIIa inhibitors within 72 hours prior to randomization.
- Platelet count <100.000/µl (<100G/l)
- Blood glucose <50mg/dl (2.8 mmol/l) or >400mg/dl (22.2mmol/l)
- Uncontrolled hypertension defined by a blood pressure > 185 mmHg systolic or >110 mmHg diastolic on at least 2 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.
- Hereditary or acquired hemorrhagic diathesis
- Gastrointestinal or urinary bleeding within 21 days prior to randomization
- Manifest or recent acute pancreatitis
- Manifest severe liver disease including hepatic failure, cirrhosis, portal hypertension and active hepatitis
- Major surgery within 14 days prior to randomization which poses a risk in the opinion of the investigator.
- Recent (within 10 days) traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood-vessel
- Exposure to a thrombolytic agent within 72 hours prior to randomization
- Hypersensitivity to alteplase or any of the excipients