Clinical trial NCT06241677: Intravenous Thrombolytic Therapy in Acute Ischemic Stroke Patients on DOAC
Official title: Intravenous Thrombolytic Therapy in Acute Ischemic Stroke Patients on Direct Oral Anticoagulants - a Prospective Multicenter Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: CVA (Cerebrovascular Accident)
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Pamela Youde Nethersole Eastern Hospital
name: Queen Mary Hospital, Hong Kong
name: Princess Margaret Hospital, Canada
name: Tuen Mun Hospital
name: The Queen Elizabeth Hospital
name: United Christian Hospital
First posted: 2024-02-05
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Presence of symptomatic intracerebral hemorrhage (ICH)
timeFrame: up to 1 year
measure: Modified Rankin Scale (mRS)
timeFrame: 3 months after CVA
Secondary outcomes:
measure: Presence of asymptomatic ICH
timeFrame: up to 1 year
measure: Presence of hemorrhagic transformation
timeFrame: up to 1 year
measure: Presence of malignant cerebral edema
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Chinese University of Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: Bonaventure Yiu Ming Ip, MB ChB
role: PRINCIPAL_INVESTIGATOR
References: