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

July 30, 2026 updated by: Insel Gruppe AG, University Hospital Bern

Safety and Efficacy of Intravenous Thrombolysis in Patients With Ischemic Stroke on Treatment With Direct Oral Anticoagulants: DO-IT - The DOAC Intravenous Thrombolysis Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

906

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Freschta Zipser-Mohammadzada, PhD
  • Phone Number: +41 31 63 2 60 83
  • Email: nctu@insel.ch

Study Locations

  • Austria
      • Eisenstadt, Austria, 7000
        • Recruiting
        • Barmherzige Brüder Krankenhaus Eisenstadt
        • Contact:
        • Principal Investigator:
          • Dimitre Staykov
      • Graz, Austria, 8036
        • Recruiting
        • Universitätsklinik für Neurologie Graz
        • Contact:
        • Principal Investigator:
          • Thomas Gattringer
        • Principal Investigator:
          • Simon Fandler-Höfler
      • Innsbruck, Austria, 6020
        • Not yet recruiting
        • Medical University of Innsbruck
        • Contact:
        • Principal Investigator:
          • Christian Boehme
      • Salzburg, Austria, 5020
        • Recruiting
        • Christian Doppler Klinik
        • Contact:
        • Principal Investigator:
          • Sebastian Mutzenbach
      • Vienna, Austria, 1090
        • Recruiting
        • Medizinische Universität Wien
        • Contact:
        • Principal Investigator:
          • Stefan Greisenegger
      • Vienna, Austria, 1020
        • Recruiting
        • Barmherzige Brüder Krankenhaus Wien
        • Contact:
        • Principal Investigator:
          • Marek Sykora
  • Belgium
      • Bruges, Belgium
        • Recruiting
        • Az Sint-Jan Brugge Av
        • Contact:
        • Principal Investigator:
          • Sofie Deblauwe
      • Brussels, Belgium
      • Brussels, Belgium
        • Recruiting
        • Cliniques Universitaires de Bruxelles
        • Contact:
          • Patrick Lamotte
          • Phone Number: +32 (0)2 555 51 52
        • Principal Investigator:
          • Noemi Ligot, MD
      • Charleroi, Belgium
        • Recruiting
        • Hôpital Civil Marie Curie
        • Contact:
        • Principal Investigator:
          • Flavio Bellante, MD
      • Ghent, Belgium
        • Recruiting
        • University Hospital Gent
        • Contact:
        • Principal Investigator:
          • Dimitri M. Hemelsoet, MD
      • Kortrijk, Belgium
        • Recruiting
        • AZ Groeninge, Campus Kennedy
        • Principal Investigator:
          • Peter Vanacker, MD
        • Contact:
      • Leuven, Belgium, 3000
      • Liège, Belgium, 4000
        • Not yet recruiting
        • CHU de Liège
        • Contact:
        • Principal Investigator:
          • Julien Ly
  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8L 2X2
        • Not yet recruiting
        • Hamilton Health Sciences
        • Principal Investigator:
          • Luciana Catanese, MD
  • Finland
      • Helsinki, Finland, 00290
        • Recruiting
        • Helsinki University Central Hospital
        • Principal Investigator:
          • Daniel Strbian
        • Contact:
  • France
      • Bordeaux, France, 33000
        • Not yet recruiting
        • CHU Bordeaux
        • Principal Investigator:
          • Igor Sibon
        • Contact:
      • Grenoble, France, 38043
        • Not yet recruiting
        • CHU Grenoble Alpes
        • Principal Investigator:
          • Olivier DETANTE
        • Contact:
      • Lille, France, 59037
        • Not yet recruiting
        • CHU de Lille
        • Contact:
        • Principal Investigator:
          • Nelly Dequatre
      • Lyon, France, 69677
        • Not yet recruiting
        • Hopital Pierre Wertheimer
        • Principal Investigator:
          • Tae-Hee Cho
        • Contact:
      • Montpellier, France, 34 295
        • Not yet recruiting
        • CHU Montpellier
        • Principal Investigator:
          • Caroline ARQUIZAN
        • Contact:
      • Nancy, France, 54035
        • Not yet recruiting
        • Chu Nancy
        • Principal Investigator:
          • Sébastien Richard
        • Contact:
      • Paris, France, 75014
        • Not yet recruiting
        • Hopital Paris Saint-Joseph
        • Principal Investigator:
          • Benjamin Maïer
        • Contact:
      • Paris, France, 75013
        • Not yet recruiting
        • AP-HP, Pitié-Salpêtrière
        • Contact:
        • Principal Investigator:
          • Sonia Alamowitch
      • Paris, France, 75014
        • Recruiting
        • GHU Paris Psychiatrie et Neurosciences, Sainte Anne
        • Principal Investigator:
          • Guillaume Turc, Dr. med.
      • Paris, France, 75019
        • Not yet recruiting
        • AP-HP, Lariboisière
        • Contact:
        • Principal Investigator:
          • Mikael Mazighi
      • Perpignan, France, 66000
        • Not yet recruiting
        • Perpignan Hospital Center
        • Principal Investigator:
          • Denis Sablot
        • Contact:
      • Strasbourg, France, 67098
        • Not yet recruiting
        • Hôpital de Hautepierre
        • Principal Investigator:
          • Valérie Wolff
        • Contact:
      • Suresnes, France, 92150
  • Germany
      • Bad Neustadt an der Saale, Germany, 97616
        • Recruiting
        • RHÖN-KLINIKUM AG - Campus Bad Neustadt
        • Principal Investigator:
          • Hassan Soda
        • Contact:
      • Bamberg, Germany, 96049
      • Bochum, Germany, 44791
      • Bottrop, Germany, 46242
      • Erfurt, Germany, 99089
        • Recruiting
        • Helios Klinikum Erfurt GmbH
        • Contact:
        • Principal Investigator:
          • Andreas Steinbrecher
      • Essen, Germany, 45131
        • Not yet recruiting
        • Alfried Krupp Krankenhaus
        • Contact:
        • Principal Investigator:
          • Roland Veltkamp
      • Frankfurt, Germany, 60590
        • Recruiting
        • Universitätsmedizin Frankfurt
        • Contact:
        • Principal Investigator:
          • Jan Hendrik Schäfer
      • Freiburg im Breisgau, Germany, 79106
        • Recruiting
        • Universitatsklinikum Freiburg
        • Contact:
        • Principal Investigator:
          • Jürgen Bardutzky
      • Giessen, Germany
        • Recruiting
        • Universitätsklinikum Gießen und Marburg GmbH
        • Contact:
        • Principal Investigator:
          • Christian Claudi, MD
      • Göttingen, Germany
        • Recruiting
        • Universitätsmedizin Göttingen, Abteilung Neurologie
        • Contact:
        • Principal Investigator:
          • Katrin Wasser, MD
      • Hamburg, Germany, 22307
        • Not yet recruiting
        • Asklepios Klinik Barmbek
        • Contact:
        • Principal Investigator:
          • Carsten Pohlmann
      • Hamburg, Germany
        • Recruiting
        • Asklepios Klinik Wandsbek
        • Contact:
        • Principal Investigator:
          • Lars Marquardt, MD
      • Heidelberg, Germany, 69120
        • Recruiting
        • Heidelberg University Hospital
        • Principal Investigator:
          • Jan C. Purrucker, MD
      • Homburg, Germany, 66421
        • Not yet recruiting
        • Universitätsklinikum des Saarlandes
        • Contact:
        • Principal Investigator:
          • Yaroslav Winter
      • Jena, Germany, 07747
        • Recruiting
        • Universitätsklinikum Jena
        • Contact:
        • Principal Investigator:
          • Albrecht Guenther
      • Kassel, Germany, 34125
      • Leipzig, Germany, 04103
      • Ludwigshafen, Germany
        • Recruiting
        • Klinikum der Stadt Ludwigshafen
        • Contact:
        • Principal Investigator:
          • Simon Nagel, MD
      • Lübeck, Germany, 23560
        • Not yet recruiting
        • Sana Kliniken Lübeck GmbH
        • Contact:
        • Principal Investigator:
          • Jens Schaumberg
      • München, Germany, 81377
        • Recruiting
        • Klinikum der Universität München
        • Contact:
        • Principal Investigator:
          • Lars Kellert
      • Rosenheim, Germany, 83022
        • Not yet recruiting
        • RoMed Klinikum Rosenheim Klinik
        • Contact:
      • Sande, Germany, 26452
        • Recruiting
        • Nordwest-Krankenhaus Sanderbusch
        • Contact:
        • Principal Investigator:
          • Pawel Kermer
      • Schleswig, Germany
        • Recruiting
        • Helios Klinik Schleswig GmbH, Klinik für Neurologie und Neurologische
        • Contact:
        • Principal Investigator:
          • Frederick Palm, MD
      • Tübingen, Germany
        • Recruiting
        • Universitätsklinikum Tübingen, Abt. Neurologie mit Schwerpunkt neurovaskuläre Erkrankungen
        • Contact:
        • Principal Investigator:
          • Annerose Mengel, MD
      • Ulm, Germany, 89081
        • Recruiting
        • Universitätsklinikum Ulm
        • Contact:
        • Principal Investigator:
          • Karl Georg Häusler
    • Baden-Wurttemberg
      • Karlsbad, Baden-Wurttemberg, Germany, 76307
        • Recruiting
        • SRH Klinikum Karlsbad-Langensteinbach GmbH
        • Contact:
        • Contact:
        • Principal Investigator:
          • Sibu Mundi, MD
  • Greece
      • Alexandroupoli, Greece, 68100
        • Not yet recruiting
        • Department of Neurology University Hospital of Alexandroupolis Democritus University of Thrace
        • Contact:
      • Athens, Greece, 12462
        • Not yet recruiting
        • "Attikon" University Hospital
        • Principal Investigator:
          • Georgios Tsivgoulis, MD, PhD
      • Athens, Greece, 11528
        • Not yet recruiting
        • Eginition Hospital
        • Contact:
      • Heraklion, Greece, 71500
        • Not yet recruiting
        • Department of Neurology, School of Medicine University of Crete
        • Contact:
          • Panayiotis D. Mitsias, MD
          • Phone Number: +302810394839
          • Email: pmitsias@uoc.gr
      • Pátrai, Greece, 265 04
        • Not yet recruiting
        • University General Hospital of Patras
        • Contact:
      • Thessaloniki, Greece, 546 36
        • Not yet recruiting
        • 2nd Department of Neurology, School of Medicine Faculty of Health Sciences, Aristotle University of Thessaloniki
        • Contact:
  • Netherlands
      • Amsterdam, Netherlands, 1105
        • Recruiting
        • Academic Medical Center Amsterdam, Department of Neurology
        • Principal Investigator:
          • Jonathan Coutinho, Dr. med.
      • Amsterdam, Netherlands, 1091
      • Arnhem, Netherlands, 6815
        • Recruiting
        • Rijnstate
        • Contact:
      • Breda, Netherlands, 4818
        • Recruiting
        • Amphia Hospital
        • Contact:
        • Principal Investigator:
          • Ishita Miah, MD
      • Dordrecht, Netherlands, 3318
        • Not yet recruiting
        • Albert Schweitzer Ziekenhuis
        • Contact:
      • Eindhoven, Netherlands, 5623
      • Groningen, Netherlands, 9700
        • Recruiting
        • University Medical Center Groningen
        • Contact:
      • Leiden, Netherlands, 2333
        • Recruiting
        • University Medical Center
        • Contact:
        • Principal Investigator:
          • Nyika Kruyt, MD
      • Maastricht, Netherlands, 6229
      • Nieuwegein, Netherlands, 3435
        • Not yet recruiting
        • St. Antonius Ziekenhuis
        • Contact:
        • Principal Investigator:
          • Joost Kerklaan, MD
      • Nijmegen, Netherlands, 6500
      • Rotterdam, Netherlands, 3045
      • Rotterdam, Netherlands, 3015
        • Not yet recruiting
        • Erasmus Medical Center
        • Contact:
        • Principal Investigator:
          • Heleen den Hertog
      • The Hague, Netherlands, 2512
        • Recruiting
        • Haaglanden MC, HMC Westeinde
        • Contact:
        • Principal Investigator:
          • Ido van den Wijngaard
      • The Hague, Netherlands, 6815
        • Recruiting
        • Haga Ziekenhuis
        • Contact:
        • Principal Investigator:
          • Jurgen Piet
      • Utrecht, Netherlands, 3584
        • Recruiting
        • University Medical Center Utrecht
        • Contact:
        • Principal Investigator:
          • Michiel Poorthuis
      • Zwolle, Netherlands, 8025
  • Norway
      • Oslo, Norway
        • Recruiting
        • Akershus Hospital
        • Contact:
          • Espen Kristoffersen, MD
        • Principal Investigator:
          • Espen Kristoffersen
  • Portugal
      • Amadora, Portugal, 2720-276
      • Coimbra, Portugal, 3004-561
      • Funchal, Portugal, 9000-177
      • Lisbon, Portugal, 1150-199
        • Recruiting
        • Lisbon Central University Hospital Centre
        • Principal Investigator:
          • Diana Aguiar de Sousa, MD, PhD
      • Lisbon, Portugal, 1449-005
      • Matosinhos Municipality, Portugal, 4464-513
        • Recruiting
        • Hospital Pedro Hispano
        • Contact:
        • Principal Investigator:
          • Vítor T. Cruz
      • Porto, Portugal, 4099-001
        • Recruiting
        • Hospital de Santo António
        • Contact:
      • Porto, Portugal, 4520-211
        • Recruiting
        • ULS de Entre Douro e Vouga
        • Contact:
        • Principal Investigator:
          • Luís Fontão
  • Spain
      • Barcelona, Spain, 08035
        • Not yet recruiting
        • Vall d'Hebron Stroke Center
        • Principal Investigator:
          • Carlos A. Molina, MD, PhD
  • Switzerland
      • Baden, Switzerland, 5404
      • Basel, Switzerland, 4031
        • Recruiting
        • University Hospital Basel
        • Contact:
        • Principal Investigator:
          • Mira Katan, Prof.
        • Sub-Investigator:
          • Gerrit Grosse, MD
      • Bern, Switzerland, 3010
        • Recruiting
        • Inselspital Bern
        • Contact:
        • Principal Investigator:
          • Thomas Meinel, MD, PhD
      • Biel, Switzerland, 2502
      • Geneva, Switzerland, 1205
        • Recruiting
        • Hôpitaux Universitaires Genève
        • Contact:
      • Lausanne, Switzerland, 1011
        • Recruiting
        • Médecin Associé Service de Neurologie Département des Neurosciences Cliniques CHUV, BH13
        • Contact:
      • Lucerne, Switzerland, 6000
        • Recruiting
        • Luzerner Kantonsspital
        • Contact:
      • Lugano, Switzerland, 6903
        • Not yet recruiting
        • Ente Ospedaliero Cantonale Istituto di Neuroscienze Cliniche della Svizzera Italiana Stroke Center EOC, Clinica di Neurologia c/o Ospedale Regionale di Lugano, sede Civico
        • Contact:
      • Nyon, Switzerland, 1260
        • Recruiting
        • Neurologue FMH, AFC EEG/ENMG
        • Contact:
        • Principal Investigator:
          • Julien Niederhäuser
      • Porto, Switzerland, 4200-319
      • Sankt Gallen, Switzerland
        • Recruiting
        • Kantonsspital St. Gallen
        • Contact:
          • Gian Marco De Marchis, Prof.
        • Principal Investigator:
          • Gian Marco De Marchis, Prof.
      • Zurich, Switzerland, 8091
        • Recruiting
        • Universitätsspital Zürich
        • Contact:
      • Zurich, Switzerland, 8032
      • Zurich, Switzerland, 8063

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Best Medical Treatment (standard of care)
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.
Experimental: Intravenous Thrombolysis + Best medical treatment (standard of care)
Patients will receive intravenous administration of Tenecteplase or Alteplase.
Drug: Tenecteplase or Alteplase
Patients randomized to intravenous thrombolysis (IVT) treatment will receive intravenous Tenecteplase or Alteplase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
90 days +/- 2 weeks after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
90 days +/- 2 weeks post-randomization
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".
24 +/- 12 hours after Intervention
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.
90 days +/- 2 weeks post-randomization

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Symptomatic intracranial hemorrhage
Time Frame: Within the first 36 hours post-randomization
Observed in clinical imaging
Within the first 36 hours post-randomization
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.
Within the first 24 hours post-randomization
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
Up to 7 to 10 days after admission or until discharge, usually 2 weeks after admission

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Insel Gruppe AG, University Hospital Bern

Investigators

  • Study Director: Thomas Meinel, MD, PhD, Insel Gruppe AG, University Hospital Bern

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 14, 2025

Primary Completion (Estimated)

January 31, 2029

Study Completion (Estimated)

April 30, 2029

Study Registration Dates

First Submitted

August 22, 2024

First Submitted That Met QC Criteria

August 22, 2024

First Posted (Actual)

August 26, 2024

Study Record Updates

Last Update Posted (Actual)

August 3, 2026

Last Update Submitted That Met QC Criteria

July 30, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-01157

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

IPDMA (individual participant data meta-analysis) of similar interventional clinical studies is planned.

IPD Sharing Time Frame

After publication of primary study results

IPD Sharing Access Criteria

Ethics clearance, agreement with the DO-IT collaboration about terms of use and authorship

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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