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.

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.