Intravenous Thrombolytic Therapy in Acute Ischemic Stroke Patients on DOAC

NCT06241677 | Recruiting DMC

• 1 other identifier: CIRB-2023-167-1
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

Brief 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)

Outcome Measures

Primary Outcomes (2)

• Presence of symptomatic intracerebral hemorrhage (ICH)

  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

• Modified Rankin Scale (mRS)

  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

Secondary Outcomes (3)

• Presence of asymptomatic ICH

  up to 1 year

• Presence of hemorrhagic transformation

  up to 1 year

• Presence of malignant cerebral edema

  up to 1 year

Study Arms (2)

IVT group

ACTIVE COMPARATOR

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

Control

NO INTERVENTION

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.

Interventions

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

Also known as: tPA or TNK

IVT group

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Queen Mary Hospital, Hong Kong: collaborator
• Princess Margaret Hospital, Canada: collaborator
• Tuen Mun Hospital: collaborator
• The Queen Elizabeth Hospital: collaborator
• United Christian Hospital: collaborator
• Chinese University of Hong Kong: lead
• Pamela Youde Nethersole Eastern Hospital: collaborator

Study Sites (1)

Chinese University of Hong Kong

Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Conditions

Stroke

Interventions

Tissue Plasminogen Activator; Tenecteplase; TNK-tissue plasminogen activator

Condition Hierarchy (Ancestors)

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

• Bonaventure Yiu Ming Ip, MB ChB

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yiu Ming Bonaventure Ip, MB ChB

CONTACT

+852-26352152; bonaventureip@cuhk.edu.hk

Trista Hung

CONTACT

+852-26352152; tristahung@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 17, 2024
• First Posted: February 5, 2024
• Study Start: April 15, 2024
• Primary Completion (Estimated): December 12, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)