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

NCT06571149 | Recruiting Phase 4 DMC

• 1 other identifier: 2024-01157
• Study Type: interventional
• Target: 906
• Locations: 12 countries
• Sites: 14

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.

Conditions

Ischemic Stroke

Keywords

DOAC; NOAC (Novel Oral Anticoagulants); Anticoagulation; r-tPA (tissue-type plasminogen activator); Alteplase; Tenecteplase; Rivaroxaban; Apixaban; Dabigatran; Edoxaban

Outcome Measures

Primary Outcomes (1)

• 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).

  90 days +/- 2 weeks after randomization

Secondary Outcomes (3)

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

  90 days +/- 2 weeks post-randomization

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

  24 +/- 12 hours after Intervention

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

  90 days +/- 2 weeks post-randomization

Other Outcomes (3)

• Rate of Symptomatic intracranial hemorrhage

  Within the first 36 hours post-randomization

• Rate of Major extracranial bleeding

  Within the first 24 hours post-randomization

• All-cause mortality

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

Study Arms (2)

Best Medical Treatment (standard of care)

NO INTERVENTION

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

Patients will receive intravenous administration of Tenecteplase or Alteplase.

Drug: Tenecteplase or Alteplase

Interventions

Tenecteplase or Alteplase DRUG

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

Intravenous Thrombolysis + Best medical treatment (standard of care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify 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 qualify 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)
• Intended treatment with endovascular reperfusion strategies

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (14)

UZ Leuven

Leuven, 3000, Belgium

NOT YET RECRUITING

Hamilton Health Sciences

Hamilton, Ontario, L8L 2X2, Canada

NOT YET RECRUITING

GHU Paris Psychiatrie et Neurosciences, Sainte Anne

Paris, 75014, France

NOT YET RECRUITING

Heidelberg University Hospital

Heidelberg, 69120, Germany

NOT YET RECRUITING

"Attikon" University Hospital

Athens, 12462, Greece

NOT YET RECRUITING

National Cerebral and Cardiovascular Center Osaka

Osaka, Kansai, 565-8565, Japan

NOT YET RECRUITING

Academic Medical Center Amsterdam, Department of Neurology

Amsterdam, 1105, Netherlands

NOT YET RECRUITING

Canterbury District Health Board

Christchurch, 8011, New Zealand

NOT YET RECRUITING

Akershus Hospital

Oslo, Norway

NOT YET RECRUITING

Lisbon Central University Hospital Centre

Lisbon, 1150-199, Portugal

NOT YET RECRUITING

Vall d'Hebron Stroke Center

Barcelona, 08035, Spain

NOT YET RECRUITING

University Hospital Basel

Basel, 4031, Switzerland

NOT YET RECRUITING

Inselspital Bern

Bern, 3010, Switzerland

RECRUITING

Kantonsspital St. Gallen

Sankt Gallen, Switzerland

RECRUITING

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tenecteplase; Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Thomas Meinel, MD, PhD

  Insel Gruppe AG, University Hospital Bern

  STUDY DIRECTOR

Central Study Contacts

Thomas Meinel, MD, PhD

CONTACT

+41 31 66 4 25 67; thomas.meinel@insel.ch

Freschta Zipser-Mohammadzada, PhD

CONTACT

+41 31 63 2 60 83; nctu@insel.ch

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2024
• First Posted: August 26, 2024
• Study Start: March 14, 2025
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): April 30, 2029
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: After publication of primary study results
• Access Criteria: Ethics clearance, agreement with the DO-IT collaboration about terms of use and authorship

Locations

CH (3); BE (1); NZ (1); FR (1); NO (1); CA (1); DE (1); GR (1); JP (1); NL (1); PT (1); ES (1)