Dual Thrombolytic Therapy With Mutant Pro-urokinase and Low Dose Alteplase for Ischemic Stroke

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.