Study design

DUMAS is a multicenter, phase II, randomized clinical trial with open-label treatment, adaptive design for dose optimization and blinded outcome assessment, comparing a low dose IV alteplase followed by IV m-pro-urokinase with usual thrombolytic treatment of alteplase alone.

Patient population

We aim to enroll 200 patients with a clinical diagnosis of ischemic stroke. Eligibility criteria are listed below.

DUMAS 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 guidelines
- Age of 18 years or older
- Written informed consent (deferred)

A potential subject who meets any of the following criteria will be excluded from participation in this study:

DUMAS 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 guidelines:
  • 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
  • Cerebral concussion 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)
  • o a copper intrauterine device
- Current Participation in any medical or surgical therapeutic trial other than DUMAS.

Randomisation and treatment

Patients will be randomly allocated to dual thrombolytic treatment with low dose alteplase followed by mutant pro-urokinase or alteplase alone (standard care) by a computer- and web-based procedure.

Primary outcome

The primary outcome is any post-intervention intracranial hemorrhage on MRI according to the Heidelberg Bleeding Classification within 24-48 hours of study drug administration.