Ischemic StrokePhase 2DUMASNCT04256473
Dual Thrombolytic Therapy With Mutant Pro-urokinase and Low Dose Alteplase for Ischemic Stroke
A Phase 2 study testing mutant pro-urokinase and Alteplase in people with Ischemic Stroke, run by Erasmus Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- mutant pro-urokinase and Alteplase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteNetherlands
- Study dates
- 10 Aug 2019to 26 May 2022
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dual Thrombolytic Therapy With Mutant Pro-urokinase (M-pro-urokinase, HisproUK) and Low Dose Alteplase for Ischemic Stroke
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
- Being tested
- mutant pro-urokinase, Alteplase
- Keywords
- Randomized Controlled Trial, Thrombolytic treatment, Intracranial hemorrhage, Mutant pro-urokinase, Ischemic stroke
- Medical subject headings
- Ischemic Stroke, Intracranial Hemorrhages
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mutant pro-urokinaseDrug
Also called HisproUK
Intravenous administration
AlteplaseDrug
Also called Actilyse
Intravenous administration
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: mutant pro-urokinase |
| Control | Active comparator | Usual care with alteplase 0.9 mg/kg in 60 minutes Receives: Drug: Alteplase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Any intracranial hemorrhage according to the Heidelberg Bleeding Classification on MRI
Measured: 24-48 hours post-treatment
Secondary outcomes (8)
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.
Measured: at 24 hours and 5-7 days post-treatment
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.
Measured: at 30 days
Infarct volume on MRI
Measured: 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
Measured: at 24-48 hours post treatment.
Secondary blood biomarkers of thrombolysis: d-dimer levels and fibrinogen levels.
Measured: 1 hour post-treatment, after 3 hours, and after 24 hours post-treatment,
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.
Measured: within 30 days
Death from any cause
Measured: Within 30 days
Major extracranial hemorrhage according to the ISTH criteria
Measured: within 24 hours of study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start10 Aug 2019
- Primary completion26 Mar 2022
- Study completion26 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- DUMAS is sponsored by an unrestricted grant from Thrombolytic Science International, paid to the institution.
- Responsible party
- Principal investigator, Nadinda van der Ende, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04256473
- Sponsor's protocol ID
- DUMAS-1.1
- Acronym
- DUMAS
- Status last verified
- Sep 2023
- First submitted
- 3 Feb 2020
- Last updated
- 7 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 37213122van 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.
PubMed 35945566