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

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ClinicalTrials.gov Identifier: NCT04256473
Recruitment Status : Recruiting
First Posted : February 5, 2020
Last Update Posted : February 17, 2020
Sponsor:
Collaborator:
DUMAS is sponsored by an unrestricted grant from Thrombolytic Science International, paid to the institution.
Information provided by (Responsible Party):
Nadinda van der Ende, Erasmus Medical Center

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : August 10, 2019
Estimated Primary Completion Date : February 1, 2021
Estimated Study Completion Date : March 1, 2021

Resource links provided by the National Library of Medicine


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 Name: HisproUK

Active Comparator: Control
Usual care with alteplase 0.9 mg/kg in 60 minutes
Drug: Alteplase
Intravenous administration
Other Name: Actilyse




Primary Outcome Measures :
  1. Any intracranial hemorrhage according to the Heidelberg Bleeding Classification on MRI [ Time Frame: 24-48 hours post-treatment ]

Secondary Outcome Measures :
  1. Score on the National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: 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.

  2. Score on the modified Rankin Scale (mRS) [ Time Frame: 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.

  3. Infarct volume on MRI [ Time Frame: at 24-48 hours ]
  4. 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. ]
  5. 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, ]
  6. Symptomatic intracranial hemorrhage (sICH) according to the Heidelberg Bleeding Classification [ Time Frame: 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.

  7. Death from any cause [ Time Frame: Within 30 days ]
  8. Major extracranial hemorrhage according to the ISTH criteria [ Time Frame: within 24 hours of study drug administration ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04256473


Locations
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Netherlands
DUMAS trial office Recruiting
Rotterdam, Netherlands, 3000 CA
Contact: DUMAS trial office    0639583967 ext 0639583967    dumas@erasmusmc.nl   
Principal Investigator: Diederik WJ Dippel, MD, PhD         
Sponsors and Collaborators
Erasmus Medical Center
DUMAS is sponsored by an unrestricted grant from Thrombolytic Science International, paid to the institution.

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Responsible Party: Nadinda van der Ende, PI: Prof. Dr. DWJ Dippel and A. van der Lugt, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT04256473    
Other Study ID Numbers: DUMAS-1.1
First Posted: February 5, 2020    Key Record Dates
Last Update Posted: February 17, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nadinda van der Ende, Erasmus Medical Center:
Randomized Controlled Trial
Thrombolytic treatment
Intracranial hemorrhage
Mutant pro-urokinase
Ischemic stroke
Additional relevant MeSH terms:
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Stroke
Cerebral Infarction
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Tissue Plasminogen Activator
Saruplase
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action