NCT04256473

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Aug 2019

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 10, 2019

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

February 3, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 5, 2020

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 26, 2022

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 26, 2022

Completed
Last Updated

September 7, 2023

Status Verified

September 1, 2023

Enrollment Period

2.6 years

First QC Date

February 3, 2020

Last Update Submit

September 5, 2023

Conditions

Ischemic Stroke

Keywords

Randomized Controlled TrialThrombolytic treatmentIntracranial hemorrhageMutant pro-urokinaseIschemic stroke

Outcome Measures

Primary Outcomes (1)

  • Any intracranial hemorrhage according to the Heidelberg Bleeding Classification on MRI

    24-48 hours post-treatment

Secondary Outcomes (8)

  • Score on the National Institutes of Health Stroke Scale (NIHSS)

    at 24 hours and 5-7 days post-treatment

  • Score on the modified Rankin Scale (mRS)

    at 30 days

  • 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,

  • +3 more secondary outcomes

Study Arms (2)

Intervention

EXPERIMENTAL

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

Control

ACTIVE COMPARATOR

Usual care with alteplase 0.9 mg/kg in 60 minutes

Drug: Alteplase

Interventions

mutant pro-urokinaseDRUG

Intravenous administration

Also known as: HisproUK
Intervention
AlteplaseDRUG

Intravenous administration

Also known as: Actilyse
Control

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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.:
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

DUMAS trial office

Rotterdam, 3000 CA, Netherlands

Location

Related Publications (2)

  • 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, Postma AA, Roosendaal SD, Krietemeijer GM, Yo LSF, de Maat MPM, Nieboer D, Del Zoppo GJ, Meurer WJ, Lingsma HF, van der Lugt A, Dippel DWJ; DUMAS Investigators. Safety and Efficacy of Dual Thrombolytic Therapy With Mutant Prourokinase and Small Bolus Alteplase for Ischemic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2023 Jul 1;80(7):714-722. doi: 10.1001/jamaneurol.2023.1262.

    PMID: 37213122DERIVED

  • 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.

    PMID: 35945566DERIVED

MeSH Terms

Conditions

Ischemic StrokeIntracranial Hemorrhages

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

StrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Serine EndopeptidasesEndopeptidasesPeptide HydrolasesHydrolasesEnzymesEnzymes and CoenzymesSerine ProteasesPlasminogen ActivatorsBlood Coagulation FactorsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsBiological Factors

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
PI: Prof. Dr. DWJ Dippel and A. van der Lugt

Study Record Dates

First Submitted

February 3, 2020

First Posted

February 5, 2020

Study Start

August 10, 2019

Primary Completion

March 26, 2022

Study Completion

May 26, 2022

Last Updated

September 7, 2023

Record last verified: 2023-09

Locations

NL(1)