Intravenous Thrombolytic Therapy in Acute Ischemic Stroke Patients on DOAC (DOAC-IVT)

February 21, 2026 updated by: Dr. IP Yiu Ming Bonaventure, Chinese University of Hong Kong

Intravenous Thrombolytic Therapy in Acute Ischemic Stroke Patients on Direct Oral Anticoagulants - A Prospective Multicenter Study

Direct oral anticoagulants (DOAC) have emerged as safe and efficacious ischemic stroke prophylaxis for non-valvular atrial fibrillation (NVAF). All four DOACs - apixaban, dabigatran, edoxaban, rivaroxaban - were associated with lower risks of major bleeding compared to warfarin. Listed as core essential medicines by the World Health Organization, DOAC prescriptions have been surging worldwide. In Hong Kong, approximately 80,000 patients received DOACs from January 2009 through December 2022 according to the Hospital Authority registry.

The widespread DOAC usage had created DOAC-specific clinical dilemmas that lack evidence-based treatment despite twenty years of prescribing experience. Ischemic stroke despite DOAC (IS-DOAC), in particular, may occur in up to 6% of DOAC users annually. Due to the in vivo anticoagulation effect, there had been concerns of intracerebral bleeding (ICH) with intravenous thrombolytic therapy (IVT) for acute IS-DOAC. Under the current guideline recommendations, most acute IS-DOAC are contraindicated to IVT (see Intravenous thrombolytic therapy), which resulted in only a small proportion of acute ISDOAC patients being able to receive IVT even if presented early. Nonetheless, our group found that majority of patients had a DOAC level of <50ng/mL only 24 hours after DOAC cessation (see work done by us), a level deemed clinically negligible and safe for thrombolytic therapy. Together with evolving clinical evidence discussed below, IS-DOAC patients maybe unnecessarily barred from IVT, thus compromised functional recovery.

With robust pharmacokinetic and retrospective clinical evidence to support, it is hypothesized that IVT are safe in IS-DOAC patient. The investigators hereby propose a prospective multicenter study to determine the efficacy and safety of IVT in acute IS-DOAC.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In this prospective cohort study, the investigators aim to recruit consecutive DOAC users with IS-DOAC who meet the inclusion criteria. The investigators aim to determine the safety and efficacy of IVT among DOAC patients with acute ischemic stroke. It is hypothesized that compared to a matched cohort of patients with acute IS-DOAC excluded from IVT, IVT in IS-DOAC patients with a last-DOAC-ingestion of 12-48 hours improves neurological outcomes with an acceptable safety profile.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
260

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Chinese University of Hong Kong
        • Contact:
        • Contact:
        • Principal Investigator:
          • Bonaventure Yiu Ming Ip, MB ChB

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Acute ischemic stroke patients with a last-known-well to presentation time within 4.5 hours
  2. Patients who took any doses of apixaban (2.5mg or 5mg twice daily), dabigatran (110mg or 150mg twice daily), edoxaban (30mg or 60mg daily) or rivaroxaban (15mg or 20mg daily) 12-48 hours before presentation
  3. National Institute of Health Stroke Scale (NIHSS) ≥ 3
  4. Alberta Stroke Programme Early CT (ASPECT) score ≥ 6
  5. Pre-morbid modified Rankin Scale (mRS) ≤ 3
  6. Patients aged ≥ 18 years old

Exclusion Criteria:

  1. Initial CT brain showing intracranial haemorrhage
  2. Contraindications to IVT according to current guideline recommendations [5], except for the use of DOAC within 12-48 hours
  3. Patients with an estimated glomerular filtration rate of ≤ 30ml/min/1.73m2
  4. Patients with bleeding propensities apart from the use of DOAC, e.g. platelet count of < 100x109/L
  5. Patients with significant head injury immediately prior to presentation

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: IVT group
For patients enrolled into the IVT group from participating centers that allow IVT in patients with last DOAC intake 12-48 hours before presentation (PWH, QEH, QMH, UCH, TMH): Either alteplase (0.6 or 0.9mg/kg, maximum dosage 90mg, intravenous infusion) or tenecteplase (0.25mg/kg, maximum dosage 25mg, intravenous infusion) will be given at discretion of the treating physician.
Drug: alteplase or tenecteplase
Either alteplase (0.6 or 0.9mg/kg, maximum dosage 90mg) or tenecteplase (0.25mg/kg, maximum dosage 25mg) will be given
Other Names:
  • tPA or TNK
No Intervention: Control
For patients enrolled into the control group from participating centers that exclude eligible patients from IVT (PMH, PYNEH): no IVT will be given unless specific antidote can be administered before IVT.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Modified Rankin Scale (mRS)
Time Frame: 3 months after CVA
To measure the degree of disability as a primary efficacy outcome, on the scale of 0-6: 0= no symptoms at all, 6=dead
3 months after CVA
Presence of symptomatic intracerebral hemorrhage (ICH)
Time Frame: up to 1 year
As primary safety outcome. By the Heidelberg Bleeding Classification, the investigators shall categorize intracranial hemorrhages into HI1, HI2, PH1, PH2, and define symptomatic ICH as blood at any site in the brain with clinical deterioration (e.g. drowsiness and increased hemiparesis) or an increase in National Institute of Health Stroke Scale (NIHSS) score of ≥ 4 points (scores ranging from 0-42, higher scores indicating greater severity.)
up to 1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Presence of asymptomatic ICH
Time Frame: up to 1 year
As seen from computer tomography (CT) and magnetic resonance imaging (MRI)
up to 1 year
Presence of hemorrhagic transformation
Time Frame: up to 1 year
As seen from computer tomography (CT) and magnetic resonance imaging (MRI)
up to 1 year
Presence of malignant cerebral edema
Time Frame: up to 1 year
As seen from computer tomography (CT) and magnetic resonance imaging (MRI)
up to 1 year

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Chinese University of Hong Kong

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Queen Mary Hospital, Hong Kong
Princess Margaret Hospital, Canada
Tuen Mun Hospital
Pamela Youde Nethersole Eastern Hospital
The Queen Elizabeth Hospital
United Christian Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Bonaventure Yiu Ming IP, MB ChB, Chinese University of Hong Kong

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 15, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 12, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 17, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 5, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 21, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CIRB-2023-167-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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