Clinical trial NCT06571149: Safety and Efficacy of Intravenous Thrombolysis in Patients With Ischemic Stroke and Direct Oral Anticoagulants Intake
Official title: Safety and Efficacy of Intravenous Thrombolysis in Patients With Ischemic Stroke on Treatment With Direct Oral Anticoagulants: DO-IT - The DOAC Intravenous Thrombolysis Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Ischemic Stroke
Keywords: DOAC
NOAC (Novel Oral Anticoagulants)
Anticoagulation
r-tPA (tissue-type plasminogen activator)
Alteplase
Tenecteplase
Rivaroxaban
Apixaban
Dabigatran
Edoxaban
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2024-08-26
Enrollment: 906
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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

Primary outcomes:
measure: Modified Rankin Scale (mRS)
timeFrame: 90 days +/- 2 weeks after randomization
Secondary outcomes:
measure: Dichotomized modified Rankin Scale (mRS) 0-2 (good functional outcome)
timeFrame: 90 days +/- 2 weeks post-randomization
measure: Change from baseline in stroke severity (National Institutes of Health Stroke Scale, NIHSS)
timeFrame: 24 +/- 12 hours after Intervention
measure: Health-related Quality of Life (EuroQol 5D-3L questionnaire)
timeFrame: 90 days +/- 2 weeks post-randomization
Other outcomes:
measure: Rate of Symptomatic intracranial hemorrhage
timeFrame: Within the first 36 hours post-randomization
measure: Rate of Major extracranial bleeding
timeFrame: Within the first 24 hours post-randomization
measure: All-cause mortality
timeFrame: Up to 7 to 10 days after admission or until discharge, usually 2 weeks after admission
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: Paris
country: France
facility: GHU Paris Psychiatrie et Neurosciences, Sainte Anne
city: Heidelberg
country: Germany
facility: Heidelberg University Hospital
city: Athens
country: Greece
facility: "Attikon" University Hospital
city: Osaka
country: Japan
facility: National Cerebral and Cardiovascular Center Osaka
state: Kansai
city: Amsterdam
country: Netherlands
facility: Academic Medical Center Amsterdam, Department of Neurology
city: Christchurch
country: New Zealand
facility: Canterbury District Health Board
city: Oslo
country: Norway
facility: Akershus Hospital
city: Lisbon
country: Portugal
facility: Lisbon Central University Hospital Centre
city: Barcelona
country: Spain
facility: Vall d'Hebron Stroke Center
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Bern
country: Switzerland
facility: Inselspital Bern
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Thomas Meinel, MD, PhD
role: STUDY_DIRECTOR
References: