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

Official 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

Overview

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.

Interventions

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

Primary outcome measures

• Modified Rankin Scale (mRS) [Time frame: 90 days +/- 2 weeks after randomization]

Secondary outcome measures (3)

• Dichotomized modified Rankin Scale (mRS) 0-2 (good functional outcome) [Time frame: 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]
• Health-related Quality of Life (EuroQol 5D-3L questionnaire) [Time frame: 90 days +/- 2 weeks post-randomization]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 26 centers

• SRH Klinikum Karlsbad-Langensteinbach GmbH — Karlsbad
• RHÖN-KLINIKUM AG - Campus Bad Neustadt — Bad Neustadt an der Saale
• Sozialstiftung Bamberg — Bamberg
• St. Josef-Hospital — Bochum
• Knappschaft Kliniken Bottrop GmbH — Bottrop
• Helios Klinikum Erfurt GmbH — Erfurt
• Alfried Krupp Krankenhaus — Essen
• Universitätsmedizin Frankfurt — Frankfurt
• … and 18 more centers

Netherlands · 17 centers

• OLVG location East — Amsterdam
• Academic Medical Center Amsterdam, Department of Neurology — Amsterdam
• Rijnstate — Arnhem
• Amphia Hospital — Breda
• Albert Schweitzer ziekenhuis — Dordrecht
• Catharina Ziekenhuis — Eindhoven
• University Medical Center Groningen — Groningen
• University Medical Center — Leiden
• … and 9 more centers

Switzerland · 14 centers

Center list to be confirmed — check the primary protocol.

France · 13 centers

• CHU Bordeaux — Bordeaux
• Chu Grenoble Alpes — Grenoble
• CHU de Lille — Lille
• Hôpital Pierre Wertheimer — Lyon
• CHU Montpellier — Montpellier
• CHU Nancy — Nancy
• AP-HP, Pitié-Salpêtrière — Paris
• GHU Paris Psychiatrie et Neurosciences, Sainte Anne — Paris
• … and 5 more centers

Belgium · 8 centers

• AZ Sint-Jan Brugge AV — Bruges
• Cliniques Universitaires de Bruxelles — Brussels
• UCL St Luc — Brussels
• Hôpital Civil Marie Curie — Charleroi
• University Hospital Gent — Ghent
• AZ Groeninge, Campus Kennedy — Kortrijk
• UZ Leuven — Leuven
• CHU de Liège — Liège

Portugal · 8 centers

• Hospital Amadora-Sintra Fernando Fonseca — Amadora
• … and 7 more centers

Austria · 6 centers

• Barmherzige Brüder Krankenhaus Eisenstadt — Eisenstadt
• Universitätsklinik für Neurologie Graz — Graz
• Medical University of Innsbruck — Innsbruck
• Christian Doppler Klinik — Salzburg
• Barmherzige Brüder Krankenhaus Wien — Vienna
• Medizinische Universität Wien — Vienna

Greece · 6 centers

• Department of Neurology University Hospital of Alexandroupolis Democritus University of Th — Alexandroupoli
• Eginition Hospital — Athens
• "Attikon" University Hospital — Athens
• Department of Neurology, School of Medicine University of Crete — Heraklion
• University General Hospital of Patras — Pátrai
• 2nd Department of Neurology, School of Medicine Faculty of Health Sciences, Aristotle Univ — Thessaloniki

Canada · 1 center

• Hamilton Health Sciences — Hamilton

Finland · 1 center

• Helsinki University Central Hospital — Helsinki

Norway · 1 center

• Akershus Hospital — Oslo

Spain · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06571149 · 2024-01157

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗