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

Ischemic Stroke Clinical Trial

— DUMAS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04256473
• Other study ID #: DUMAS-1.1
• Status: Completed
• Phase: Phase 2
• Start date: August 10, 2019
• Est. completion date: May 26, 2022

Study information

• Verified date: September 2023
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: May 26, 2022
• Est. primary completion date: March 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• mutant pro-urokinase
Intravenous administration
• Alteplase
Intravenous administration

Locations

Country	Name	City	State
Netherlands	DUMAS trial office	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	DUMAS is sponsored by an unrestricted grant from Thrombolytic Science International, paid to the institution.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Any intracranial hemorrhage according to the Heidelberg Bleeding Classification on MRI		24-48 hours post-treatment
Secondary	Score on the National Institutes of Health Stroke Scale (NIHSS)	The NIHSS measures neurological deficit, ranging from 0 to 42, with higher scores indicating more severe neurological deficit.	at 24 hours and 5-7 days post-treatment
Secondary	Score on the modified Rankin Scale (mRS)	The mRS is an ordinal scale ranging from 0 (no symptoms) to 6 (death) measuring the degree of disability or dependence in everyday life.	at 30 days
Secondary	Infarct volume on MRI		at 24-48 hours
Secondary	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	Secondary blood biomarkers of thrombolysis: d-dimer levels and fibrinogen levels.		1 hour post-treatment, after 3 hours, and after 24 hours post-treatment,
Secondary	Symptomatic intracranial hemorrhage (sICH) according to the Heidelberg Bleeding Classification	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.	within 30 days
Secondary	Death from any cause		Within 30 days
Secondary	Major extracranial hemorrhage according to the ISTH criteria		within 24 hours of study drug administration

External Links

•   DUMAS website