Safety and Efficacy of Intravenous Thrombolysis in Patients With Ischemic Stroke and Direct Oral Anticoagulants Intake
- Registration Number
- NCT06571149
- Lead Sponsor
- Insel Gruppe AG, University Hospital Bern
- Brief Summary
DO-IT is an international, multicenter, prospective, two-arm, randomized, open label, blinded endpoint superiority trial determining the safety and efficacy of intravenous thrombolysis (IVT) in participants experiencing an acute ischemic stroke (AIS) with recent (within the last 48 hours) intake of direct oral anticoagulant (DOAC). For this purpose, 906 adult participants experiencing an AIS with recent DOAC intake will be enrolled at several high-volume international stroke centers and randomly assigned in a ratio of 1:1 to one of two treatment arms: (1) IVT and standard of care/best medical treatment or (2) standard of care/best medical treatment. The DO-IT trial is a definitive test of the hypothesis that IVT is superior to standard of care for achieving better outcome at 90 days in AIS participants with recent DOAC intake.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 906
-
Informed consent (deferred consent when possible according to national legislation)
-
AIS eligible to receive intravenous alteplase/tenecteplase as per standard of care disabling according to the judgement of the treating physician
-
DOAC ingestion within 48 hours prior to enrollment, or patient with an ongoing prescription of DOAC but exact time point of last intake is unknown.
-
Either
- Can be randomized within 4 hours 15 minutes and treated within 4 hours 30 minutes of last known well time OR
- MRI showing a pattern of "DWI-FLAIR-mismatch", i.e. acute ischemic lesion visibly on DWI ("positive DWI") but no marked parenchymal hyperintensity visible on FLAIR ("negative FLAIR") indicative of an acute ischemic lesion ≤4.5 hours of age AND Treatment can be started within 4.5 hours of symptom recognition (e.g., awakening).
-
Contra-indications to IVT by the current standard of care of the treating physicians with the exception of recent DOAC intake as specified above.
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Intended reversal by specific or unspecific reversal agents
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Pregnancy or lactating women. To be reasonable sure to exclude women with ongoing pregnancy, women are not considered of childbearing potential if they fulfill the following criteria
- Age > 55 years OR
- Age < 55 years and at least 12 months since last menstrual period OR
- Have had a documented surgical sterilization
-
Patient < 18 years of age (since the benefit of IVT is unproven in this population)
Since the benefit of IVT might be smaller in patients in which additional endovascular treatment is planned, the investigators will cap patients with intended mechanical thrombectomy at 20% of the trial population. If this number is reached, the following additional exclusion criterion will be applied:
- Intended treatment with endovascular reperfusion strategies
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intravenous Thrombolysis + Best medical treatment (standard of care) Tenecteplase or Alteplase Patients will receive intravenous administration of Tenecteplase or Alteplase.
- Primary Outcome Measures
Name Time Method Modified Rankin Scale (mRS) 90 days +/- 2 weeks after randomization Modified Rankin Scale is a scale that runs from 0-6, running from perfect health without symptoms (0) to death (6).
- Secondary Outcome Measures
Name Time Method Dichotomized modified Rankin Scale (mRS) 0-2 (good functional outcome) 90 days +/- 2 weeks post-randomization Modified Rankin Scale is a scale that runs from 0-6, running from perfect health without symptoms (0) to death (6).
Change from baseline in stroke severity (National Institutes of Health Stroke Scale, NIHSS) 24 +/- 12 hours after Intervention The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. Thus, 0 (minimum score) means "no symptoms", whereas 42 (maximum score) means "severe stroke".
Health-related Quality of Life (EuroQol 5D-3L questionnaire) 90 days +/- 2 weeks post-randomization The EuroQol 5D-3L (EuroQol 5 Dimensions with each 3 Levels) measures health-related Quality of Life.
Trial Locations
- Locations (14)
Inselspital Bern
🇨🇭Bern, Switzerland
UZ Leuven
🇧🇪Leuven, Belgium
Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
GHU Paris Psychiatrie et Neurosciences, Sainte Anne
🇫🇷Paris, France
Heidelberg University Hospital
🇩🇪Heidelberg, Germany
"Attikon" University Hospital
🇬🇷Athens, Greece
National Cerebral and Cardiovascular Center Osaka
🇯🇵Osaka, Kansai, Japan
Academic Medical Center Amsterdam, Department of Neurology
🇳🇱Amsterdam, Netherlands
Canterbury District Health Board
🇳🇿Christchurch, New Zealand
Akershus Hospital
🇳🇴Oslo, Norway
Lisbon Central University Hospital Centre
🇵🇹Lisbon, Portugal
Vall d'Hebron Stroke Center
🇪🇸Barcelona, Spain
University Hospital Basel
🇨🇭Basel, Switzerland
Kantonsspital St. Gallen
🇨🇭St. Gallen, Switzerland