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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 : April 7, 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

Tracking Information
First Submitted Date  ICMJE February 3, 2020
First Posted Date  ICMJE February 5, 2020
Last Update Posted Date April 7, 2020
Actual Study Start Date  ICMJE August 10, 2019
Estimated Primary Completion Date February 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2020)
Any intracranial hemorrhage according to the Heidelberg Bleeding Classification on MRI [ Time Frame: 24-48 hours post-treatment ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2020)
  • 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.
  • 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.
  • Infarct volume on MRI [ Time Frame: 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 [ Time Frame: at 24-48 hours post treatment. ]
  • 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, ]
  • 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.
  • Death from any cause [ Time Frame: Within 30 days ]
  • Major extracranial hemorrhage according to the ISTH criteria [ Time Frame: within 24 hours of study drug administration ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2020)
  • 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.
  • 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.
  • Infarct volume on MRI [ Time Frame: 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 [ Time Frame: at 24-48 hours post treatment. ]
  • 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, ]
  • 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.
  • Death from any cause [ Time Frame: Within 30 days ]
    Number of participants that died during the study.
  • Major extracranial hemorrhage according to the ISTH criteria [ Time Frame: within 24 hours of study drug administration ]
    Number of participants with a major extracranial hemorrhage according tot he ISTH criteria.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dual Thrombolytic Therapy With Mutant Pro-urokinase and Low Dose Alteplase for Ischemic Stroke
Official Title  ICMJE Dual Thrombolytic Therapy With Mutant Pro-urokinase (M-pro-urokinase, HisproUK) and Low Dose Alteplase for 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Ischemic Stroke
Intervention  ICMJE
  • Drug: mutant pro-urokinase
    Intravenous administration
    Other Name: HisproUK
  • Drug: Alteplase
    Intravenous administration
    Other Name: Actilyse
Study Arms  ICMJE
  • 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).

    Intervention: Drug: mutant pro-urokinase
  • Active Comparator: Control
    Usual care with alteplase 0.9 mg/kg in 60 minutes
    Intervention: Drug: Alteplase
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 7, 2020)
200
Original Estimated Enrollment  ICMJE
 (submitted: February 4, 2020)
25
Estimated Study Completion Date  ICMJE March 1, 2021
Estimated Primary Completion Date February 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04256473
Other Study ID Numbers  ICMJE DUMAS-1.1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Nadinda van der Ende, Erasmus Medical Center
Study Sponsor  ICMJE Erasmus Medical Center
Collaborators  ICMJE DUMAS is sponsored by an unrestricted grant from Thrombolytic Science International, paid to the institution.
Investigators  ICMJE Not Provided
PRS Account Erasmus Medical Center
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP