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

NCT ID: NCT04256473

Last Updated: 2023-09-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-10
• Study Completion Date: 2022-05-26

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.

Conditions

Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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).

Group Type: EXPERIMENTAL

mutant pro-urokinase

Intervention Type: DRUG

Intravenous administration

Control

Usual care with alteplase 0.9 mg/kg in 60 minutes

Group Type: ACTIVE_COMPARATOR

Alteplase

Intervention Type: DRUG

Intravenous administration

Interventions

mutant pro-urokinase

Intravenous administration

Intervention Type: DRUG

Alteplase

Intravenous administration

Intervention Type: DRUG

Other Intervention Names

HisproUK; Actilyse

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

DUMAS is sponsored by an unrestricted grant from Thrombolytic Science International, paid to the institution.

UNKNOWN

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Nadinda van der Ende

PI: Prof. Dr. DWJ Dippel and A. van der Lugt

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

DUMAS trial office

Rotterdam, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 37213122 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35945566 (View on PubMed)

Other Identifiers

DUMAS-1.1

Identifier Type: -

Identifier Source: org_study_id