Safety and Efficacy of Intravenous Thrombolysis in Patients With Ischemic Stroke and Direct Oral Anticoagulants Intake

What this study is about

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.

Who can join (things the study team will check)

✅ You may be able to join if…

• 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).

🚫 You may not be able to join if…

• 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
  • 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

Where this trial is running

• 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

+ 2 more sites.

Who to contact

Thomas Meinel, MD, PhD · +41 31 66 4 25 67 · thomas.meinel@insel.ch

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT06571149.