Safety and Efficacy of Intravenous Thrombolysis in Patients With Ischemic Stroke and Direct Oral Anticoagulants Intake
NCT Number: NCT06571149
Acronym: DO-IT
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Ischemic Stroke
Interventions: DRUG: Tenecteplase or Alteplase
Sponsor: Insel Gruppe AG, University Hospital Bern
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 906
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-10-31
Completion Date: 2029-04-30
Locations: UZ Leuven, Leuven, 3000, Belgium|Hamilton Health Sciences, Hamilton, Ontario, L8L 2X2, Canada|GHU Paris Psychiatrie et Neurosciences, Sainte Anne, Paris, 75014, France|Heidelberg University Hospital, Heidelberg, 69120, Germany|"Attikon" University Hospital, Athens, 12462, Greece|National Cerebral and Cardiovascular Center Osaka, Osaka, Kansai, 565-8565, Japan|Academic Medical Center Amsterdam, Department of Neurology, Amsterdam, 1105, Netherlands|Canterbury District Health Board, Christchurch, 8011, New Zealand|Akershus Hospital, Oslo, Norway|Lisbon Central University Hospital Centre, Lisbon, 1150-199, Portugal|Vall d'Hebron Stroke Center, Barcelona, 08035, Spain|University Hospital Basel, Basel, 4031, Switzerland|Kantonsspital St. Gallen, St. Gallen, Switzerland

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.

Primary Outcome Measures: Modified Rankin Scale (mRS), Modified Rankin Scale is a scale that runs from 0-6, running from perfect health without symptoms (0) to death (6)., 90 days +/- 2 weeks after randomization
Secondary Outcome Measures: Dichotomized modified Rankin Scale (mRS) 0-2 (good functional outcome), Modified Rankin Scale is a scale that runs from 0-6, running from perfect health without symptoms (0) to death (6)., 90 days +/- 2 weeks post-randomization|Change from baseline in stroke severity (National Institutes of Health Stroke Scale, NIHSS), 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"., 24 +/- 12 hours after Intervention|Health-related Quality of Life (EuroQol 5D-3L questionnaire), The EuroQol 5D-3L (EuroQol 5 Dimensions with each 3 Levels) measures health-related Quality of Life., 90 days +/- 2 weeks post-randomization
Other Outcome Measures: Rate of Symptomatic intracranial hemorrhage, Observed in clinical imaging, Within the first 36 hours post-randomization|Rate of Major extracranial bleeding, Defined as clinically overt bleeding that is accompanied by one or more of the following (according to International Society on Thrombosis and Haemostasis definitions):

* Decrease in haemoglobin of ≥ 2g / dl over a 24-hour period
* Transfusion of ≥ 2 units of packed red blood cells
* Occurring in a critical part of the body (intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal)
* In order for bleeding (e.g. gastrointestinal) in a critical area or organ to be classified as a major extracranial bleeding it must be associated with a symptomatic clinical presentation., Within the first 24 hours post-randomization|All-cause mortality, Death from any cause, Up to 7 to 10 days after admission or until discharge, usually 2 weeks after admission