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NCT Number: NCT06571149

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

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.

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Key information

Conditions

Ischemic Stroke Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Nervous System Diseases Stroke Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

UZ Leuven, Leuven, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Tenecteplase or Alteplase

Drug

Patients randomized to intravenous thrombolysis (IVT) treatment will receive intravenous Tenecteplase or Alteplase.

Primary outcomes

  1. Modified Rankin Scale (mRS)

    Time frame: 90 days +/- 2 weeks after randomization

    Modified Rankin Scale is a scale that runs from 0-6, running from perfect health without symptoms (0) to death (6).

Secondary outcomes

  1. Dichotomized modified Rankin Scale (mRS) 0-2 (good functional outcome)

    Time frame: 90 days +/- 2 weeks post-randomization

    Modified Rankin Scale is a scale that runs from 0-6, running from perfect health without symptoms (0) to death (6).

  2. Change from baseline in stroke severity (National Institutes of Health Stroke Scale, NIHSS)

    Time frame: 24 +/- 12 hours after Intervention

    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".

  3. Health-related Quality of Life (EuroQol 5D-3L questionnaire)

    Time frame: 90 days +/- 2 weeks post-randomization

    The EuroQol 5D-3L (EuroQol 5 Dimensions with each 3 Levels) measures health-related Quality of Life.

Other outcomes

  1. Rate of Symptomatic intracranial hemorrhage

    Time frame: Within the first 36 hours post-randomization

    Observed in clinical imaging

  2. Rate of Major extracranial bleeding

    Time frame: Within the first 24 hours post-randomization

    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.

  3. All-cause mortality

    Time frame: Up to 7 to 10 days after admission or until discharge, usually 2 weeks after admission

    Death from any cause

Study contacts

Contact information is provided by the study sponsor or research team.

Freschta Zipser-Mohammadzada, PhD

CONTACT

[email protected]

+41 31 63 2 60 83

Thomas Meinel, MD, PhD

CONTACT

[email protected]

+41 31 66 4 25 67

Sponsors and collaborators

Lead sponsor

Insel Gruppe AG, University Hospital Bern

Other

Registry information

Official study 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

Acronym: DO-IT

Important dates

Study start
2025
Primary completion
2029
Study completion
2029
First posted
Aug 26, 2024
Registry last updated
Mar 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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