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

• Status: Recruiting
• Trial end date: 2022-07-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Erasmus Medical Center; Nadinda van der Ende
• Collaborator: DUMAS is sponsored by an unrestricted grant from Thrombolytic Science International, paid to the institution.
• Treatments: Fibrinolytic Agents; Saruplase; Tissue Plasminogen Activator

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.