Safety and Efficacy of Intravenous Thrombolysis in Patients With Ischemic Stroke and Direct Oral Anticoagulants Intake
DO-IT
1 other identifier
interventional
906
12 countries
102
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Mar 2025
Longer than P75 for phase_4
102 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 22, 2024
CompletedFirst Posted
Study publicly available on registry
August 26, 2024
CompletedStudy Start
First participant enrolled
March 14, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2029
August 3, 2026
July 1, 2026
3.9 years
August 22, 2024
July 30, 2026
Conditions
Keywords
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 INTERVENTIONPatients 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)
EXPERIMENTALPatients will receive intravenous administration of Tenecteplase or Alteplase.
Interventions
Patients randomized to intravenous thrombolysis (IVT) treatment will receive intravenous Tenecteplase or Alteplase.
Eligibility Criteria
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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (102)
Barmherzige Brüder Krankenhaus Eisenstadt
Eisenstadt, 7000, Austria
Universitätsklinik für Neurologie Graz
Graz, 8036, Austria
Medical University of Innsbruck
Innsbruck, 6020, Austria
Christian Doppler Klinik
Salzburg, 5020, Austria
Barmherzige Brüder Krankenhaus Wien
Vienna, 1020, Austria
Medizinische Universität Wien
Vienna, 1090, Austria
AZ Sint-Jan Brugge AV
Bruges, Belgium
Cliniques Universitaires de Bruxelles
Brussels, Belgium
UCL St Luc
Brussels, Belgium
Hôpital Civil Marie Curie
Charleroi, Belgium
University Hospital Gent
Ghent, Belgium
AZ Groeninge, Campus Kennedy
Kortrijk, Belgium
UZ Leuven
Leuven, 3000, Belgium
CHU de Liège
Liège, 4000, Belgium
Hamilton Health Sciences
Hamilton, Ontario, L8L 2X2, Canada
Helsinki University Central Hospital
Helsinki, 00290, Finland
CHU Bordeaux
Bordeaux, 33000, France
Chu Grenoble Alpes
Grenoble, 38043, France
CHU de Lille
Lille, 59037, France
Hôpital Pierre Wertheimer
Lyon, 69677, France
CHU Montpellier
Montpellier, 34 295, France
CHU Nancy
Nancy, 54035, France
AP-HP, Pitié-Salpêtrière
Paris, 75013, France
GHU Paris Psychiatrie et Neurosciences, Sainte Anne
Paris, 75014, France
Hôpital Paris Saint-Joseph
Paris, 75014, France
AP-HP, Lariboisière
Paris, 75019, France
Perpignan Hospital Center
Perpignan, 66000, France
Hôpital de Hautepierre
Strasbourg, 67098, France
Hôpital FOCH
Suresnes, 92150, France
SRH Klinikum Karlsbad-Langensteinbach GmbH
Karlsbad, Baden-Wurttemberg, 76307, Germany
RHÖN-KLINIKUM AG - Campus Bad Neustadt
Bad Neustadt an der Saale, 97616, Germany
Sozialstiftung Bamberg
Bamberg, 96049, Germany
St. Josef-Hospital
Bochum, 44791, Germany
Knappschaft Kliniken Bottrop GmbH
Bottrop, 46242, Germany
Helios Klinikum Erfurt GmbH
Erfurt, 99089, Germany
Alfried Krupp Krankenhaus
Essen, 45131, Germany
Universitätsmedizin Frankfurt
Frankfurt, 60590, Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
Universitätsklinikum Gießen und Marburg GmbH
Giessen, Germany
Universitätsmedizin Göttingen, Abteilung Neurologie
Göttingen, Germany
Asklepios Klinik Barmbek
Hamburg, 22307, Germany
Asklepios Klinik Wandsbek
Hamburg, Germany
Heidelberg University Hospital
Heidelberg, 69120, Germany
Universitätsklinikum des Saarlandes
Homburg, 66421, Germany
Universitätsklinikum Jena
Jena, 07747, Germany
Klinikum Kassel
Kassel, 34125, Germany
Universität Leipzig
Leipzig, 04103, Germany
Klinikum der Stadt Ludwigshafen
Ludwigshafen, Germany
Sana Kliniken Lübeck GmbH
Lübeck, 23560, Germany
Klinikum der Universität München
München, 81377, Germany
RoMed Klinikum Rosenheim Klinik
Rosenheim, 83022, Germany
Nordwest-Krankenhaus Sanderbusch
Sande, 26452, Germany
Helios Klinik Schleswig GmbH, Klinik für Neurologie und Neurologische
Schleswig, Germany
Universitätsklinikum Tübingen, Abt. Neurologie mit Schwerpunkt neurovaskuläre Erkrankungen
Tübingen, Germany
Universitätsklinikum Ulm
Ulm, 89081, Germany
Department of Neurology University Hospital of Alexandroupolis Democritus University of Thrace
Alexandroupoli, 68100, Greece
Eginition Hospital
Athens, 11528, Greece
"Attikon" University Hospital
Athens, 12462, Greece
Department of Neurology, School of Medicine University of Crete
Heraklion, 71500, Greece
University General Hospital of Patras
Pátrai, 265 04, Greece
2nd Department of Neurology, School of Medicine Faculty of Health Sciences, Aristotle University of Thessaloniki
Thessaloniki, 546 36, Greece
OLVG location East
Amsterdam, 1091, Netherlands
Academic Medical Center Amsterdam, Department of Neurology
Amsterdam, 1105, Netherlands
Rijnstate
Arnhem, 6815, Netherlands
Amphia Hospital
Breda, 4818, Netherlands
Albert Schweitzer ziekenhuis
Dordrecht, 3318, Netherlands
Catharina Ziekenhuis
Eindhoven, 5623, Netherlands
University Medical Center Groningen
Groningen, 9700, Netherlands
University Medical Center
Leiden, 2333, Netherlands
University Medical Center
Maastricht, 6229, Netherlands
St. Antonius Ziekenhuis
Nieuwegein, 3435, Netherlands
Radboud University Nijmegen Medical Center
Nijmegen, 6500, Netherlands
Erasmus Medical Center
Rotterdam, 3015, Netherlands
Franciscus Gasthuis
Rotterdam, 3045, Netherlands
Haaglanden MC, HMC Westeinde
The Hague, 2512, Netherlands
Haga Ziekenhuis
The Hague, 6815, Netherlands
University Medical Center Utrecht
Utrecht, 3584, Netherlands
Isala Hospital
Zwolle, 8025, Netherlands
Akershus Hospital
Oslo, Norway
Hospital Amadora-Sintra Fernando Fonseca
Amadora, 2720-276, Portugal
Hospitais da Universidade de Coimbra
Coimbra, 3004-561, Portugal
Hospital Dr. Nélio Mendonça
Funchal, 9000-177, Portugal
Lisbon Central University Hospital Centre
Lisbon, 1150-199, Portugal
Hospital Egas Moinz
Lisbon, 1449-005, Portugal
Hospital Pedro Hispano
Matosinhos Municipality, 4464-513, Portugal
Hospital de Santo António
Porto, 4099-001, Portugal
ULS de Entre Douro e Vouga
Porto, 4520-211, Portugal
Vall d'Hebron Stroke Center
Barcelona, 08035, Spain
Kantonsspital Baden AG
Baden, 5404, Switzerland
University Hospital Basel
Basel, 4031, Switzerland
Inselspital Bern
Bern, 3010, Switzerland
MEDIN La Tour
Biel, 2502, Switzerland
Hôpitaux Universitaires Genève
Geneva, 1205, Switzerland
Médecin Associé Service de Neurologie Département des Neurosciences Cliniques CHUV, BH13
Lausanne, 1011, Switzerland
Luzerner Kantonsspital
Lucerne, 6000, Switzerland
Ente Ospedaliero Cantonale Istituto di Neuroscienze Cliniche della Svizzera Italiana Stroke Center EOC, Clinica di Neurologia c/o Ospedale Regionale di Lugano, sede Civico
Lugano, 6903, Switzerland
Neurologue FMH, AFC EEG/ENMG
Nyon, 1260, Switzerland
Hospital de São João
Porto, 4200-319, Switzerland
Kantonsspital St. Gallen
Sankt Gallen, Switzerland
Klinik Hirslanden
Zurich, 8032, Switzerland
Stadtspital Zürich
Zurich, 8063, Switzerland
Universitätsspital Zürich
Zurich, 8091, Switzerland
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Thomas Meinel, MD, PhD
Insel Gruppe AG, University Hospital Bern
Central Study Contacts
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
August 3, 2026
Record last verified: 2026-07
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
IPDMA (individual participant data meta-analysis) of similar interventional clinical studies is planned.