Safety and Efficacy of Intravenous Thrombolysis in Patients With Ischemic Stroke and Direct Oral Anticoagulants Intake (DO-IT)

Insel Gruppe AG, University Hospital Bern

Status and phase: Enrolling; Phase 4

Conditions: Ischemic Stroke

Treatments: Drug: Tenecteplase or Alteplase

Study type: Interventional

Funder types: Other

Identifiers

NCT06571149

2024-01157

Details and patient eligibility

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.

Enrollment: 906 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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906 participants in 2 patient groups

Best Medical Treatment (standard of care)

No Intervention group

Description:

Patients will receive Standard of care/Best medical treatment according to local applicable guidelines, including the current American Heart Association/American Stroke Association (AHA/ASA) and European Stroke Organisation/ European Society of Minimally Invasive Neurological Therapy (ESO/ESMINT) guidelines.

Intravenous Thrombolysis + Best medical treatment (standard of care)

Experimental group

Description:

Patients will receive intravenous administration of Tenecteplase or Alteplase.

Treatment:

Drug: Tenecteplase or Alteplase