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NCT Number: NCT06241677

Intravenous Thrombolytic Therapy in Acute Ischemic Stroke Patients on DOAC

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.

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Key information

Conditions

CVA (Cerebrovascular Accident) Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Nervous System Diseases Stroke Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Acute ischemic stroke patients with a last-known-well to presentation time within 4.5 hours
  • 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
  • National Institute of Health Stroke Scale (NIHSS) ≥ 3
  • Alberta Stroke Programme Early CT (ASPECT) score ≥ 6
  • Pre-morbid modified Rankin Scale (mRS) ≤ 3
  • Patients aged ≥ 18 years old

Exclusion criteria

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

Treatment and study plan

alteplase or tenecteplase

Drug

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

Primary outcomes

  1. 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.)

  2. 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

Secondary outcomes

  1. Presence of asymptomatic ICH

    Time frame: up to 1 year

    As seen from computer tomography (CT) and magnetic resonance imaging (MRI)

  2. Presence of hemorrhagic transformation

    Time frame: up to 1 year

    As seen from computer tomography (CT) and magnetic resonance imaging (MRI)

  3. Presence of malignant cerebral edema

    Time frame: up to 1 year

    As seen from computer tomography (CT) and magnetic resonance imaging (MRI)

Study contacts

Contact information is provided by the study sponsor or research team.

Trista Hung

CONTACT

[email protected]

+852-26352152

Yiu Ming Bonaventure Ip, MB ChB

CONTACT

[email protected]

+852-26352152

Sponsors and collaborators

Lead sponsor

Chinese University of Hong Kong

Other

Collaborators

  • Pamela Youde Nethersole Eastern Hospital
  • Princess Margaret Hospital, Canada
  • Queen Mary Hospital, Hong Kong
  • The Queen Elizabeth Hospital
  • Tuen Mun Hospital
  • United Christian Hospital

Registry information

Official study title

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

Acronym: DOAC-IVT

Important dates

Study start
2024
Primary completion
2028
Study completion
2029
First posted
Feb 5, 2024
Registry last updated
Feb 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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