Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants

NCT06556446 | Recruiting FDA Drug

• 1 other identifier: 2023-01175
• Study Type: observational
• Target: 2,800
• Locations: 15 countries
• Sites: 33

Brief Summary

DO-IT is an international, prospective observational registry evaluating whether the administration of intravenous thrombolysis (IVT) is safe and improves functional outcome in ischemic stroke patients with recent direct oral anticoagulant (DOAC) intake. For this purpose, information on 2800 adult participants experiencing an acute ischemic stroke will be obtained at several high-volume international stroke centers and divided into three groups: IVT with recent DOACs intake (DOAC+IVT), and recent DOAC intake not receiving IVT (DOAC) as well as anonymized patients without DOAC receiving IVT. The patients are followed up for 90 days after the index event. treatment recommendations from the described observations. The investigators hypothesize that also more liberal decisions for IVT in patients with recent DOAC intake are not associated with an increased risk for symptomatic intracerebral hemorrhage (sICH) and result in better functional outcome at 3 month.

Conditions

Ischemic Stroke

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants with symptomatic intracerebral hemorrhage (sICH)

  Defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage.

  Within 36 hours after IVT

• Dichotomized good functional outcome (mRS 0-2)

  Modified Rankin Scale from 0 (no disability) to 6 (death)

  At day 90 or return to baseline (+/- 2 weeks) after admission

Secondary Outcomes (5)

• Rate of IVT among IVT-eligible DOAC patients

  Through study completion, an average of 2 years

• All-cause mortality, major bleeding and orolingual edema

  From date of randomization until the date of all-cause mortality, major bleeding or orolingual edema, whichever came first, assessed up to 7 days.

• Categorical shift in the modified Rankin Scale (mRS)

  At Day 90 (+/-2 weeks) after admission

• Stroke severity (NIHSS)

  At 24 hours ±8 hours

• Ischemic stroke volume at 24 hours (mL)

  At 24 hours ±8 hours

Study Arms (3)

DOAC+IVT

Acute ischemic Stroke patients with recent DOACs intake receive IVT.

Drug: Tenecteplase and Alteplase

DOAC

Acute ischemic Stroke patients with recent DOAC intake do not receive IVT.

IVT Controls

Acute ischemic Stroke patients without recent DOAC intake receive IVT.

Interventions

Tenecteplase and Alteplase DRUG

The timepoints, dose, and type of IVT will be collected as well as any complications occuring.

DOAC+IVT

Eligibility Criteria

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

Study Population

The in- and exclusion criteria emulate a target trial, thus the investigators want to study a population that is - except from recent DOAC ingestion - eligible for IVT as per standard of care.

You may qualify if:

• Clinical diagnosis of acute ischemic stroke with indication for IVT according to applicable guidelines
• Time from symptom onset or last known well \<12 hours
• Admission NIHSS of 2 points or more
• either DOAC ingestion within 48 hours prior to expected timepoint of IVT bolus, or patient with an ongoing prescription of DOAC, but exact timepoint of last intake not verifiable in the emergency setting. (regardless of whether intravenous thrombolysis was given) OR DOAC prescription (any intake within the last 7 days) and receiving intravenous thrombolysis
• Informed consent (if obtainable and in those international sites where this is legally required) for the prospective part

You may not qualify if:

• Patient refused the use of biological data for research purposes (Switzerland)
• Any acute or subacute intracranial hemorrhage (ICH) identified by admission CT or MRI on brain scan
• Documentation of any other absolute contraindications to IVT in the medical record
• Significant pre-stroke disability (mRS score of 5), including known advanced dementia
• Known (serious) sensitivity to Alteplase/Tenecteplase or any of the excipients
• Pregnancy or lactating women.

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Swiss Stroke Trialist Association: collaborator
• Swiss Stroke Registry: collaborator

Study Sites (33)

Medical University of Innsbruck

Innsbruck, Austria

NOT YET RECRUITING

Cliniques Universitaires Saint Luc

Brussels, Belgium

NOT YET RECRUITING

UZ Leuven

Leuven, 3000, Belgium

NOT YET RECRUITING

The University of British Columbia | Vancouver General Hospital

Vancouver, Canada

NOT YET RECRUITING

CHU Caen

Caen, France

NOT YET RECRUITING

Nordwest-Krankenhaus Sanderbusch

Sanderbusch, Germany

NOT YET RECRUITING

Universitäsklinikum Tübingen

Tübingen, Germany

NOT YET RECRUITING

Dept. of Medicine, University of Thessaly

Larissa, Thessaly, 41110, Greece

RECRUITING

A.O.R.N. Antonio Cardarelli Hospital

Naples, Italy

NOT YET RECRUITING

Ospedali Riuniti Hospital

Palermo, Italy

NOT YET RECRUITING

Ospedale "Bufalini", Cesena

Perugia, Italy

RECRUITING

AUSL-IRCCS di Reggio Emilia

Reggio Emilia, Italy

NOT YET RECRUITING

Akershus Hospital

Oslo, Norway

NOT YET RECRUITING

Hospital de Egas Moniz

Lisbon, Portugal

NOT YET RECRUITING

Clinical Centre of Serbia, University Hospital Belgrade

Belgrade, Serbia

RECRUITING

National University Hospital

Singapore, 119228, Singapore

RECRUITING

Ljubljana University Medical Centre

Ljubljana, Slovenia

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

RECRUITING

Hospital Universitari de Bellvitge

Barcelona, Spain

NOT YET RECRUITING

Kantonsspital Aarau

Aarau, Switzerland

RECRUITING

Unispital Basel

Basel, Switzerland

RECRUITING

Inselspital Bern, University Hospital Bern

Bern, Switzerland

RECRUITING

HFR Fribourg

Fribourg, Switzerland

RECRUITING

University Hospital Geneva

Geneva, Switzerland

RECRUITING

CHUV Lausanne

Lausanne, Switzerland

RECRUITING

Kantonsspital Lucerne

Lucerne, Switzerland

RECRUITING

EOC Lugano

Lugano, Switzerland

RECRUITING

Hôpital Neuchâtelois

Neuchâtel, Switzerland

RECRUITING

Kantonsspital St. Gallen

Sankt Gallen, Switzerland

RECRUITING

Hirslanden Zurich

Zurich, Switzerland

RECRUITING

University Hospital Zurich

Zurich, Switzerland

RECRUITING

Imperial College London NHS Trust

London, United Kingdom

NOT YET RECRUITING

King'S College Hospital Nhs Foundation Trust

London, United Kingdom

NOT YET 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: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 90 Days
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2024
• First Posted: August 16, 2024
• Study Start: January 1, 2024
• Primary Completion: March 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 16, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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

NO (1); GB (2); CA (1); PT (1); SE (1); GR (1); IT (4); BE (2); CH (12); ES (2); FR (1); SG (1); AU (1); SL (1); DE (2)