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

Sponsor

Erasmus Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04256473

Collaborator

DUMAS is sponsored by an unrestricted grant from Thrombolytic Science International, paid to the institution. (Other)

200

Enrollment

Location

Arms

35.7

Anticipated Duration (Months)

5.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Drug: mutant pro-urokinase Drug: Alteplase	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Dual Thrombolytic Therapy With Mutant Pro-urokinase (M-pro-urokinase, HisproUK) and Low Dose Alteplase for Ischemic Stroke

Actual Study Start Date :

Aug 10, 2019

Anticipated Primary Completion Date :

May 31, 2022

Anticipated Study Completion Date :

Jul 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Bolus of IV alteplase (5 mg) followed by continuous infusion of HisproUK 40 mg/hr during 60 minutes. Depending on results of interim analyses, the alternate dose may be revised to a lower dose (30mg/hr during 60 minutes) or a higher dose (50mg/hr during 60 minutes).	Drug: mutant pro-urokinase Intravenous administration Other Names: HisproUK
Active Comparator: Control Usual care with alteplase 0.9 mg/kg in 60 minutes	Drug: Alteplase Intravenous administration Other Names: Actilyse

Arm

Intervention/Treatment

Experimental: Intervention

Bolus of IV alteplase (5 mg) followed by continuous infusion of HisproUK 40 mg/hr during 60 minutes. Depending on results of interim analyses, the alternate dose may be revised to a lower dose (30mg/hr during 60 minutes) or a higher dose (50mg/hr during 60 minutes).

Drug: mutant pro-urokinase

Intravenous administration

Other Names:

HisproUK

Active Comparator: Control

Usual care with alteplase 0.9 mg/kg in 60 minutes

Drug: Alteplase

Intravenous administration

Other Names:

Actilyse

Outcome Measures

Primary Outcome Measures

Any intracranial hemorrhage according to the Heidelberg Bleeding Classification on MRI [24-48 hours post-treatment]

Secondary Outcome Measures

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]
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.]
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]
Major extracranial hemorrhage according to the ISTH criteria [within 24 hours of study drug administration]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.