Overview
Randomized controlled phase II trial to test the safety and preliminary efficacy of a dual thrombolytic treatment consisting of a small intravenous (IV) bolus of alteplase followed by IV infusion of mutant pro-urokinase against usual treatment with IV alteplase in patients presenting with ischemic stroke.
Eligibility
Inclusion Criteria:
- A clinical diagnosis of ischemic stroke;
- A score of at least 1 on the NIH Stroke Scale;
- CT ruling out intracranial hemorrhage;
- Treatment possible within 4.5 hours from symptom onset or last seen well;
- Meet the criteria for standard treatment for IV alteplase according to national guidelines27;
- Age of 18 years or older;
- Written informed consent (deferred).
Exclusion Criteria:
- Candidate for endovascular thrombectomy (i.e., a proximal intracranial large artery occlusion on CTA);
- Contra-indication for treatment with IV alteplase according to national guidelines27:
- Arterial blood pressure exceeding 185/110 mmHg and not responding to treatment
- Blood glucose less than 2.7 or over 22.2 mmol/L
- Cerebral infarction in the previous 6 weeks with residual neurological deficit or signs of recent infarction on neuro-imaging
- Head trauma in the previous 4 weeks
- Major surgery or serious trauma in the previous 2 weeks
- Gastrointestinal or urinary tract hemorrhage in the previous 2 weeks
- Previous intracerebral hemorrhage
- Use of anticoagulant with INR exceeding 1.7 or APTT exceeding 50 seconds
- Known thrombocyte count less than 90 x 109 /L
- Treatment with direct thrombin or factor X inhibitors, unless specific antidotum has been given, i.e. idarucizumab in case of dabigatran use.
- Pre-stroke disability which interferes with the assessment of functional outcome at 90 days, i.e. mRS > 2;
- Known pregnancy or if pregnancy cannot be excluded, i.e. did not have intercourse for > 6 months and no clinical signs of pregnancy, adequate use of any contraceptive method (e.g. intrauterine devices) or sterilization of the subject herself.
- Contra-indication for an MRI scan, i.e.:
- an MRI incompatible pacemaker, ICD, pacing wires and loop records
- metallic foreign bodies (e.g. intra-ocular)
- prosthetic heart valves
- blood vessel clips, coils or stents
- an implanted electronic and/or magnetic implant or pump (e.g. neurostimulator)
- cochlear implants
- mechanical implants (implanted less than 6 weeks ago)
- a copper intrauterine device
- Current Participation in any medical or surgical therapeutic trial other than DUMAS.