Ischemic Stroke
Conditions
Keywords
Randomized Controlled Trial, Thrombolytic treatment, Intracranial hemorrhage, Mutant pro-urokinase, Ischemic stroke
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.
Interventions
DRUGmutant pro-urokinase
Intravenous administration
DRUGAlteplase
Intravenous administration
Sponsors
DUMAS is sponsored by an unrestricted grant from Thrombolytic Science International, paid to the institution.
Erasmus Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Any intracranial hemorrhage according to the Heidelberg Bleeding Classification on MRI | 24-48 hours post-treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Score on the National Institutes of Health Stroke Scale (NIHSS) | at 24 hours and 5-7 days post-treatment | The NIHSS measures neurological deficit, ranging from 0 to 42, with higher scores indicating more severe neurological deficit. |
| Score on the modified Rankin Scale (mRS) | at 30 days | The mRS is an ordinal scale ranging from 0 (no symptoms) to 6 (death) measuring the degree of disability or dependence in everyday life. |
| Infarct volume on MRI | at 24-48 hours | — |
| Major extracranial hemorrhage according to the ISTH criteria | within 24 hours of study drug administration | — |
| Secondary blood biomarkers of thrombolysis: d-dimer levels and fibrinogen levels. | 1 hour post-treatment, after 3 hours, and after 24 hours post-treatment, | — |
| Symptomatic intracranial hemorrhage (sICH) according to the Heidelberg Bleeding Classification | within 30 days | sICH is defined as any intracranial hemorrhage followed by a neurological deterioration that can be attributed to that hemorrhage, defined as an increase of \>= 4 points on the NIHSS or \>= 2 points on a specific NIHSS item. |
| Death from any cause | Within 30 days | — |
| Change (pre-treatment vs. post-treatment) in abnormal perfusion volume based on TTP/MTT maps measured with CT perfusion at baseline and MRI | at 24-48 hours post treatment. | — |
Countries
Netherlands
Outcome results
None listed