Clinical trial NCT04256473: Dual Thrombolytic Therapy With Mutant Pro-urokinase and Low Dose Alteplase for Ischemic Stroke
Official title: Dual Thrombolytic Therapy With Mutant Pro-urokinase (M-pro-urokinase, HisproUK) and Low Dose Alteplase for Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ischemic Stroke
Keywords: Randomized Controlled Trial
Thrombolytic treatment
Intracranial hemorrhage
Mutant pro-urokinase
Ischemic stroke
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: DUMAS is sponsored by an unrestricted grant from Thrombolytic Science International, paid to the institution.
First posted: 2020-02-05
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 criteria: 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.

Primary outcomes:
measure: Any intracranial hemorrhage according to the Heidelberg Bleeding Classification on MRI
timeFrame: 24-48 hours post-treatment
Secondary outcomes:
measure: Score on the National Institutes of Health Stroke Scale (NIHSS)
timeFrame: at 24 hours and 5-7 days post-treatment
measure: Score on the modified Rankin Scale (mRS)
timeFrame: at 30 days
measure: Infarct volume on MRI
timeFrame: at 24-48 hours
measure: Change (pre-treatment vs. post-treatment) in abnormal perfusion volume based on TTP/MTT maps measured with CT perfusion at baseline and MRI
timeFrame: at 24-48 hours post treatment.
measure: Secondary blood biomarkers of thrombolysis: d-dimer levels and fibrinogen levels.
timeFrame: 1 hour post-treatment, after 3 hours, and after 24 hours post-treatment,
measure: Symptomatic intracranial hemorrhage (sICH) according to the Heidelberg Bleeding Classification
timeFrame: within 30 days
measure: Death from any cause
timeFrame: Within 30 days
measure: Major extracranial hemorrhage according to the ISTH criteria
timeFrame: within 24 hours of study drug administration
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: DUMAS trial office
Study officials:
References:
citation: van der Ende NAM, Roozenbeek B, Smagge LEM, Luijten SPR, Aerden LAM, Kraayeveld P, van den Wijngaard IR, Lycklama A Nijeholt GJ, den Hertog HM, Flach HZ, Wallace AC, Gurewich V, Del Zoppo GJ, Meurer WJ, Lingsma HF, van der Lugt A, Dippel DWJ; DUMAS Investigators. Dual thrombolytic therapy with mutant pro-urokinase and small bolus alteplase for ischemic stroke (DUMAS): study protocol for a multicenter randomized controlled phase II trial. Trials. 2022 Aug 9;23(1):641. doi: 10.1186/s13063-022-06596-z.