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.
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
Contra-indications to IVT by the current standard of care of the treating physicians with the exception of recent DOAC intake as specified above.
Intended reversal by specific or unspecific reversal agents
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
Parallel
Tenecteplase or Alteplase
DrugPatients randomized to intravenous thrombolysis (IVT) treatment will receive intravenous Tenecteplase or Alteplase.
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).
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).
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".
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.
Rate of Symptomatic intracranial hemorrhage
Observed in clinical imaging
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.
All-cause mortality
Death from any cause
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