brain infarction Ischemic Stroke
Conditions
Interventions
Bolus of IV alteplase (5 mg) followed by continuous IV infusion of the study
medication: m-pro-urokinase 40 mg/hr during 60 minutes (initial dose).
Depending on results of interim analyses, the alte
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - A clinical diagnosis of acute ischemic stroke; - A score of at least 1 on the NIH Stroke Scale; - CT or MRI ruling out intracranial hemorrhage; -Treatment is possible o within 4.5 hours from symptom onset or last seen well, or o between 4.5 to 12 hours from symptom onset or last seen well, if the infarct core is less than 25 mL and a penumbra is at least the same size as the infarct core (i.e. total ischemic volume/infarct core mismatch >= 2.0),5 or 3) * In case of lacunar syndrome,25 if there is a diffusion-weighted imaging and FLAIR mismatch4;* - Meet the criteria for standard treatment for IV alteplase according to national guidelines; - Contra-indication for an MRI scan (e.g., an MRI incompatible pacemaker and metal foreign bodies) - Age of 18 years or older; - Written informed consent (deferred).
Exclusion criteria
Exclusion criteria: - Candidate for endovascular thrombectomy (i.e., no proximal intracranial large artery occlusion on CTA or MRA) - Contra-indication for treatment with IValteplase - Pre-stroke disability which interferes with the assessment of functional outcome at 30 days, i.e. mRS > 2. - Known pregnancy or if pregnancy cannot be excluded, i.e. adequate use of any contraceptive method (e.g. intrauterine devices) or sterilization of the subject herself - Participation in medical or surgical intervention trials other than DUMAS (or MR ASAP/ARTEMIS)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary outcome is any post-intervention intracranial haemorrhage on MRI according to the Heidelberg Bleeding Classification within 24-48 hours of study drug administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary clinical outcomes - Score on the National Institute of Health Stroke Scale (NIHSS) assessed at 24 hours and at 5-7 days post-treatment. - Improvement of at least 4 points on NIHSS at 24 hours compared to baseline, or (near) complete recovery (NIHSS 0 or 1). - Score on the modified Rankin Scale (mRS) assessed at 30 days (-7 days to +14 days) post-treatment. - All possible dichotomizations of the mRS as assessed at 30 days (-7 days to +14 days) post-treatment. This includes complete recovery (mRS 0 vs 1-6), excellent functional outcome (mRS 0-1 vs 2-6), good functional outcome (mRS 0-3 vs 4-6), and handicapped survival (mRS 0-4 vs 5-6) and survival in any condition (mRS 0-5 vs 6). Secondary neuroimaging outcomes - Infarct volume measured with MRI (DWI) at 24-48 hours post-treatment. - Change (pre-treatment vs. post-treatment) in abnormal perfusion volume based on TTP/MTT maps measured with CT perfusion at baseline and MRI at 24-48 hours post treatment. Secondary blood biomarker outcomes - Secondary blood biomarkers of thrombolysis at 1 hour, 3 hours and 24 hours after treatment, including d-dimeres and fibrinogen. - Change in blood biomarkers of thrombolysis from baseline to 24 hours, including d-dimeres and fibrinogen. Safety outcomes - Symptomatic intracranial hemorrhage (sICH) according to the Heidelberg Bleeding Classification within the follow-up period defined by the last follow-up contact at 30 days5 - Death from any cause including intracranial hemorrhage within 30 days (-7 days or +14 days) (this is equivalent to handicapped survival (mRS 0-4 vs 5-6) and survival in any condition (mRS 0-5 vs 6). - Major extracranial hemorrhage according to the ISTH criteria within 24 hours of study drug administration. | — |
Countries
Netherlands
Outcome results
None listed