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
© 2022. The Author(s)..
BACKGROUND: The effectiveness of alteplase for ischemic stroke treatment is limited, partly due to the occurrence of intracranial and extracranial hemorrhage. Mutant pro-urokinase (m-proUK) does not deplete fibrinogen and lyses fibrin only after induction with alteplase. Therefore, this treatment has the potential to be safer and more efficacious than treatment with alteplase alone. The aim of this study is to assess the safety and efficacy of thrombolytic treatment consisting of a small bolus alteplase followed by m-proUK compared with standard thrombolytic treatment with alteplase in patients presenting with ischemic stroke.
METHODS: DUMAS is a multicenter, phase II trial with a prospective randomized open-label blinded end-point (PROBE) design, and an adaptive design for dose optimization. Patients with ischemic stroke, who meet the criteria for treatment with intravenous (IV) alteplase can be included. Patients eligible for endovascular thrombectomy are excluded. Patients are randomly assigned (1:1) to receive a bolus of IV alteplase (5mg) followed by a continuous IV infusion of m-proUK (40 mg/h during 60 min) or usual care with alteplase (0.9 mg/kg). Depending on the results of interim analyses, the dose of m-proUK may be revised to a lower dose (30 mg/h during 60 min) or a higher dose (50 mg/h during 60 min). We aim to include 200 patients with a final diagnosis of ischemic stroke. The primary outcome is any post-intervention intracranial hemorrhage (ICH) on neuroimaging at 24 h according to the Heidelberg Bleeding Classification, analyzed with binary logistic regression. Efficacy outcomes include stroke severity measured with the National Institutes of Health Stroke Scale (NIHSS) at 24 h and 5-7 days, score on the modified Rankin scale (mRS) assessed at 30 days, change (pre-treatment vs. post-treatment) in abnormal perfusion volume, and blood biomarkers of thrombolysis at 24 h. Secondary safety endpoints include symptomatic intracranial hemorrhage, death, and major extracranial hemorrhage. This trial will use a deferred consent procedure.
DISCUSSION: When dual thrombolytic therapy with a small bolus alteplase and m-proUK shows the anticipated effect on the outcome, this will lead to a 13% absolute reduction in the occurrence of ICH in patients with ischemic stroke.
TRIAL REGISTRATION: NL7409 (November 26, 2018)/NCT04256473 (February 5, 2020).
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
|---|---|
| Enthalten in: |
Trials - 23(2022), 1 vom: 09. Aug., Seite 641 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
van der Ende, Nadinda A M [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 11.08.2022 Date Revised 29.07.2023 published: Electronic ClinicalTrials.gov: NCT04256473 Citation Status MEDLINE |
|---|
| doi: |
10.1186/s13063-022-06596-z |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM344649474 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM344649474 | ||
| 003 | DE-627 | ||
| 005 | 20231226023251.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s13063-022-06596-z |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1148.xml |
| 035 | |a (DE-627)NLM344649474 | ||
| 035 | |a (NLM)35945566 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a van der Ende, Nadinda A M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dual thrombolytic therapy with mutant pro-urokinase and small bolus alteplase for ischemic stroke (DUMAS) |b study protocol for a multicenter randomized controlled phase II trial |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 11.08.2022 | ||
| 500 | |a Date Revised 29.07.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04256473 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a BACKGROUND: The effectiveness of alteplase for ischemic stroke treatment is limited, partly due to the occurrence of intracranial and extracranial hemorrhage. Mutant pro-urokinase (m-proUK) does not deplete fibrinogen and lyses fibrin only after induction with alteplase. Therefore, this treatment has the potential to be safer and more efficacious than treatment with alteplase alone. The aim of this study is to assess the safety and efficacy of thrombolytic treatment consisting of a small bolus alteplase followed by m-proUK compared with standard thrombolytic treatment with alteplase in patients presenting with ischemic stroke | ||
| 520 | |a METHODS: DUMAS is a multicenter, phase II trial with a prospective randomized open-label blinded end-point (PROBE) design, and an adaptive design for dose optimization. Patients with ischemic stroke, who meet the criteria for treatment with intravenous (IV) alteplase can be included. Patients eligible for endovascular thrombectomy are excluded. Patients are randomly assigned (1:1) to receive a bolus of IV alteplase (5mg) followed by a continuous IV infusion of m-proUK (40 mg/h during 60 min) or usual care with alteplase (0.9 mg/kg). Depending on the results of interim analyses, the dose of m-proUK may be revised to a lower dose (30 mg/h during 60 min) or a higher dose (50 mg/h during 60 min). We aim to include 200 patients with a final diagnosis of ischemic stroke. The primary outcome is any post-intervention intracranial hemorrhage (ICH) on neuroimaging at 24 h according to the Heidelberg Bleeding Classification, analyzed with binary logistic regression. Efficacy outcomes include stroke severity measured with the National Institutes of Health Stroke Scale (NIHSS) at 24 h and 5-7 days, score on the modified Rankin scale (mRS) assessed at 30 days, change (pre-treatment vs. post-treatment) in abnormal perfusion volume, and blood biomarkers of thrombolysis at 24 h. Secondary safety endpoints include symptomatic intracranial hemorrhage, death, and major extracranial hemorrhage. This trial will use a deferred consent procedure | ||
| 520 | |a DISCUSSION: When dual thrombolytic therapy with a small bolus alteplase and m-proUK shows the anticipated effect on the outcome, this will lead to a 13% absolute reduction in the occurrence of ICH in patients with ischemic stroke | ||
| 520 | |a TRIAL REGISTRATION: NL7409 (November 26, 2018)/NCT04256473 (February 5, 2020) | ||
| 650 | 4 | |a Clinical Trial Protocol | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Alteplase | |
| 650 | 4 | |a Ischemic stroke | |
| 650 | 4 | |a Mutant pro-urokinase | |
| 650 | 4 | |a Randomized controlled trial | |
| 650 | 4 | |a Thrombolytic treatment | |
| 650 | 7 | |a Fibrinolytic Agents |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 650 | 7 | |a Tissue Plasminogen Activator |2 NLM | |
| 650 | 7 | |a EC 3.4.21.68 |2 NLM | |
| 650 | 7 | |a Urokinase-Type Plasminogen Activator |2 NLM | |
| 650 | 7 | |a EC 3.4.21.73 |2 NLM | |
| 650 | 7 | |a saruplase |2 NLM | |
| 650 | 7 | |a U5NH2JV64T |2 NLM | |
| 700 | 1 | |a Roozenbeek, Bob |e verfasserin |4 aut | |
| 700 | 1 | |a Smagge, Lucas E M |e verfasserin |4 aut | |
| 700 | 1 | |a Luijten, Sven P R |e verfasserin |4 aut | |
| 700 | 1 | |a Aerden, Leo A M |e verfasserin |4 aut | |
| 700 | 1 | |a Kraayeveld, Petra |e verfasserin |4 aut | |
| 700 | 1 | |a van den Wijngaard, Ido R |e verfasserin |4 aut | |
| 700 | 1 | |a Lycklama À Nijeholt, Geert J |e verfasserin |4 aut | |
| 700 | 1 | |a den Hertog, Heleen M |e verfasserin |4 aut | |
| 700 | 1 | |a Flach, H Zwenneke |e verfasserin |4 aut | |
| 700 | 1 | |a Wallace, Alexis C |e verfasserin |4 aut | |
| 700 | 1 | |a Gurewich, Victor |e verfasserin |4 aut | |
| 700 | 1 | |a Del Zoppo, Gregory J |e verfasserin |4 aut | |
| 700 | 1 | |a Meurer, William J |e verfasserin |4 aut | |
| 700 | 1 | |a Lingsma, Hester F |e verfasserin |4 aut | |
| 700 | 1 | |a van der Lugt, Aad |e verfasserin |4 aut | |
| 700 | 1 | |a Dippel, Diederik W J |e verfasserin |4 aut | |
| 700 | 0 | |a DUMAS Investigators |e verfasserin |4 aut | |
| 700 | 1 | |a Dippel, Diederik |e investigator |4 oth | |
| 700 | 1 | |a van der Lugt, Aad |e investigator |4 oth | |
| 700 | 1 | |a van der Ende, Nadinda |e investigator |4 oth | |
| 700 | 1 | |a Roozenbeek, Bob |e investigator |4 oth | |
| 700 | 1 | |a de Maat, Moniek |e investigator |4 oth | |
| 700 | 1 | |a Aerden, Leo |e investigator |4 oth | |
| 700 | 1 | |a van den Wijngaard, Ido |e investigator |4 oth | |
| 700 | 1 | |a den Hertog, Heleen |e investigator |4 oth | |
| 700 | 1 | |a Kraayeveld, Petra |e investigator |4 oth | |
| 700 | 1 | |a Lycklama A Nijeholt, Geert |e investigator |4 oth | |
| 700 | 1 | |a Flach, Zwenneke |e investigator |4 oth | |
| 700 | 1 | |a Hill, Michael |e investigator |4 oth | |
| 700 | 1 | |a Rempel, Jeremy |e investigator |4 oth | |
| 700 | 1 | |a Lowe, Ann |e investigator |4 oth | |
| 700 | 1 | |a Lingsma, Hester |e investigator |4 oth | |
| 700 | 1 | |a Nieboer, Daan |e investigator |4 oth | |
| 700 | 1 | |a Del Zoppo, Gregory |e investigator |4 oth | |
| 700 | 1 | |a Rijken, Dingeman |e investigator |4 oth | |
| 700 | 1 | |a Cohen, Adam |e investigator |4 oth | |
| 700 | 1 | |a Gurewich, Victor |e investigator |4 oth | |
| 700 | 1 | |a van der Lugt, Aad |e investigator |4 oth | |
| 700 | 1 | |a Smagge, Lucas |e investigator |4 oth | |
| 700 | 1 | |a Sterrenberg, Martin |e investigator |4 oth | |
| 700 | 1 | |a El Ghannouti, Naziha |e investigator |4 oth | |
| 700 | 1 | |a Priem, Debby |e investigator |4 oth | |
| 700 | 1 | |a Batenburg, Monique |e investigator |4 oth | |
| 700 | 1 | |a Ponjee, Eva |e investigator |4 oth | |
| 700 | 1 | |a Eilander, Rieke |e investigator |4 oth | |
| 700 | 1 | |a de Meris, Joke |e investigator |4 oth | |
| 700 | 1 | |a Dofferhoff-Vermeulen, Tamara |e investigator |4 oth | |
| 700 | 1 | |a den Hartog, Sanne |e investigator |4 oth | |
| 700 | 1 | |a Kremer, Stijn |e investigator |4 oth | |
| 700 | 1 | |a Heiligers, Leontien |e investigator |4 oth | |
| 700 | 1 | |a Lansbergen-Engel, Angela |e investigator |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Trials |d 2006 |g 23(2022), 1 vom: 09. Aug., Seite 641 |w (DE-627)NLM161320430 |x 1745-6215 |7 nnns |
| 773 | 1 | 8 | |g volume:23 |g year:2022 |g number:1 |g day:09 |g month:08 |g pages:641 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s13063-022-06596-z |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 23 |j 2022 |e 1 |b 09 |c 08 |h 641 | ||