Intravenous Thrombolytic Therapy in Acute Ischemic Stroke Patients on DOAC

Summary

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.

Conditions

• CVA (Cerebrovascular Accident)

Interventions

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

Sponsors & Collaborators

• Pamela Youde Nethersole Eastern Hospital

  collaborator OTHER

• Queen Mary Hospital, Hong Kong

  collaborator OTHER

• Princess Margaret Hospital, Canada

  collaborator OTHER

• Tuen Mun Hospital

  collaborator OTHER_GOV

• The Queen Elizabeth Hospital

  collaborator OTHER

• United Christian Hospital

  collaborator OTHER

• Chinese University of Hong Kong

  lead OTHER

Principal Investigators

• Bonaventure Yiu Ming Ip, MB ChB · Chinese University of Hong Kong

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-04-15

Primary Completion

2028-12-12

Completion

2029-03-31

Countries

• Hong Kong

Study Locations