Intravenous Thrombolytic Therapy in Acute Ischemic Stroke Patients on DOAC

CVA (Cerebrovascular Accident) Clinical Trial

— DOAC-IVT  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06241677
• Other study ID #: CIRB-2023-167-1
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 5, 2024
• Est. completion date: March 31, 2029

Study information

• Verified date: February 2024
• Source: Chinese University of Hong Kong
• Contact: Yiu Ming Bonaventure Ip
• Phone: +85226352152
• Email: bonaventureip[@]cuhk.edu.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 260
• Est. completion date: March 31, 2029
• Est. primary completion date: December 12, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• CVA (Cerebrovascular Accident)
• Ischemic Stroke
• Stroke

Intervention

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

Locations

Country	Name	City	State
Hong Kong	Chinese University of Hong Kong	Hong Kong

Sponsors (7)

Lead Sponsor	Collaborator
Chinese University of Hong Kong	Pamela Youde Nethersole Eastern Hospital, Princess Margaret Hospital, Canada, Queen Mary Hospital, Hong Kong, The Queen Elizabeth Hospital, Tuen Mun Hospital, United Christian Hospital

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Presence of asymptomatic ICH	As seen from computer tomography (CT) and magnetic resonance imaging (MRI)	up to 1 year
Secondary	Presence of hemorrhagic transformation	As seen from computer tomography (CT) and magnetic resonance imaging (MRI)	up to 1 year
Secondary	Presence of malignant cerebral edema	As seen from computer tomography (CT) and magnetic resonance imaging (MRI)	up to 1 year