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

Primary Purpose

Ischemic Stroke

Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
mutant pro-urokinase
Alteplase
Sponsored by
Erasmus Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring Randomized Controlled Trial, Thrombolytic treatment, Intracranial hemorrhage, Mutant pro-urokinase, Ischemic stroke

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • DUMAS trial office

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intervention

Control

Arm Description

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).

Usual care with alteplase 0.9 mg/kg in 60 minutes

Outcomes

Primary Outcome Measures

Any intracranial hemorrhage according to the Heidelberg Bleeding Classification on MRI

Secondary Outcome Measures

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.
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.
Infarct volume on MRI
Change (pre-treatment vs. post-treatment) in abnormal perfusion volume based on TTP/MTT maps measured with CT perfusion at baseline and MRI
Secondary blood biomarkers of thrombolysis: d-dimer levels and fibrinogen levels.
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.
Death from any cause
Major extracranial hemorrhage according to the ISTH criteria

Full Information

First Posted
February 3, 2020
Last Updated
September 5, 2023
Sponsor
Erasmus Medical Center
Collaborators
DUMAS is sponsored by an unrestricted grant from Thrombolytic Science International, paid to the institution.
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1. Study Identification

Unique Protocol Identification Number
NCT04256473
Brief Title
Dual Thrombolytic Therapy With Mutant Pro-urokinase and Low Dose Alteplase for Ischemic Stroke
Acronym
DUMAS
Official Title
Dual Thrombolytic Therapy With Mutant Pro-urokinase (M-pro-urokinase, HisproUK) and Low Dose Alteplase for Ischemic Stroke
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
August 10, 2019 (Actual)
Primary Completion Date
March 26, 2022 (Actual)
Study Completion Date
May 26, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center
Collaborators
DUMAS is sponsored by an unrestricted grant from Thrombolytic Science International, paid to the institution.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke
Keywords
Randomized Controlled Trial, Thrombolytic treatment, Intracranial hemorrhage, Mutant pro-urokinase, Ischemic stroke

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Experimental
Arm Description
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).
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Usual care with alteplase 0.9 mg/kg in 60 minutes
Intervention Type
Drug
Intervention Name(s)
mutant pro-urokinase
Other Intervention Name(s)
HisproUK
Intervention Description
Intravenous administration
Intervention Type
Drug
Intervention Name(s)
Alteplase
Other Intervention Name(s)
Actilyse
Intervention Description
Intravenous administration
Primary Outcome Measure Information:
Title
Any intracranial hemorrhage according to the Heidelberg Bleeding Classification on MRI
Time Frame
24-48 hours post-treatment
Secondary Outcome Measure Information:
Title
Score on the National Institutes of Health Stroke Scale (NIHSS)
Description
The NIHSS measures neurological deficit, ranging from 0 to 42, with higher scores indicating more severe neurological deficit.
Time Frame
at 24 hours and 5-7 days post-treatment
Title
Score on the modified Rankin Scale (mRS)
Description
The mRS is an ordinal scale ranging from 0 (no symptoms) to 6 (death) measuring the degree of disability or dependence in everyday life.
Time Frame
at 30 days
Title
Infarct volume on MRI
Time Frame
at 24-48 hours
Title
Change (pre-treatment vs. post-treatment) in abnormal perfusion volume based on TTP/MTT maps measured with CT perfusion at baseline and MRI
Time Frame
at 24-48 hours post treatment.
Title
Secondary blood biomarkers of thrombolysis: d-dimer levels and fibrinogen levels.
Time Frame
1 hour post-treatment, after 3 hours, and after 24 hours post-treatment,
Title
Symptomatic intracranial hemorrhage (sICH) according to the Heidelberg Bleeding Classification
Description
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.
Time Frame
within 30 days
Title
Death from any cause
Time Frame
Within 30 days
Title
Major extracranial hemorrhage according to the ISTH criteria
Time Frame
within 24 hours of study drug administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
DUMAS trial office
City
Rotterdam
ZIP/Postal Code
3000 CA
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35945566
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.
Results Reference
derived
Links:
URL
https://dumas-trial.nl/
Description
DUMAS website

Learn more about this trial

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

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