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