Treatment Outcomes of Direct Oral Anticoagulants in Cerebral Venous Thrombosis in Vietnam

Official title

Treatment Outcomes of Direct Oral Anticoagulants in Cerebral Venous Thrombosis: A Prospective Observational Study in Vietnam

Overview

This prospective, single-arm observational cohort study aims to evaluate the real-world effectiveness and safety of direct oral anticoagulants (DOACs), specifically dabigatran or rivaroxaban, in patients with cerebral venous thrombosis (CVT). The study will be conducted at Bach Mai Hospital, a national tertiary stroke referral center in Hanoi, Vietnam. A minimum of 69 adults with radiologically confirmed CVT will be enrolled between June 2025 and June 2027. All participants must have received therapeutic-dose heparin during the acute phase and will be transitioned to a DOAC within 5 to 15 days, per physician judgment. All treatments are part of routine care; no investigational drugs are used. The primary outcome is a composite of major bleeding (per ISTH criteria) or recurrent venous thromboembolism (VTE) within 6 months. Secondary outcomes include: functional outcome (Modified Rankin Scale), venous sinus recanalization, all-cause mortality, serial D-dimer levels, post-CVT chronic headache, health-related quality of life (EQ-5D-5L), clinically relevant non-major bleeding (CRNMB), symptomatic recurrent VTE, arterial thrombotic events, and early treatment discontinuation. This study aims to generate real-world data supporting DOAC use in CVT, particularly in Asian populations where prospective evidence is limited.

Detailed description

Cerebral venous thrombosis (CVT) is an uncommon yet potentially life-threatening cerebrovascular condition. Direct oral anticoagulants (DOACs) are increasingly adopted for CVT management, supported by recent trials (e.g., RESPECT-CVT, CHOICE-CVT, SECRET) and observational cohorts. However, prospective real-world data, especially in low- and middle-income countries like Vietnam, remain scarce.

This single-center, prospective, single-arm observational study aims to assess the safety and effectiveness of DOACs (dabigatran or rivaroxaban) in routine clinical practice among CVT patients at Bach Mai Hospital-a leading tertiary referral center in northern Vietnam.

Eligible participants are adults (≥18 years) with radiologically confirmed CVT who received therapeutic-dose heparin during the acute phase and are transitioned to a DOAC between days 5 and 15. Patients will be followed for 6 months, with scheduled evaluations of:

Clinical outcomes

D-dimer levels

Neuroimaging for venous sinus recanalization

Functional status (Modified Rankin Scale)

Health-related quality of life (EQ-5D-5L)

Safety outcomes including major bleeding, CRNMB, symptomatic recurrent VTE, arterial events, and chronic headache

Early treatment discontinuation and its causes (e.g., adverse events, patient decision)

Findings from this study will contribute important real-world evidence to guide clinical practice, especially in Asian populations underrepresented in existing prospective research.

Interventions

• Drug Dabigatran
  Dabigatran will be initiated between 5 and 15 days after therapeutic-dose heparin in patients with cerebral venous thrombosis (CVT), based on clinical judgment. It is administered as part of routine clinical care.
• Drug Rivaroxaban
  Rivaroxaban will be initiated between 5 and 15 days after therapeutic-dose heparin in patients with cerebral venous thrombosis (CVT), based on clinical judgment. It is administered as part of routine clinical care.

Primary outcome measures

• Composite of major bleeding or recurrent venous thromboembolism [Time frame: Within 6 months after CVT diagnosis]

Secondary outcome measures (11)

• Mortality Rate [Time frame: At 6 months after CVT diagnosis]
• Functional outcome [Time frame: At 3 and 6 months after after CVT diagnosis]
• Number of participants with major bleeding events [Time frame: At 3 and 6 months after CVT diagnosis]
• Number of participants with clinically relevant non-major bleeding (CRNMB) events [Time frame: At 3 and 6 months after CVT diagnosis]
• Number of participants with symptomatic recurrent venous thromboembolism (VTE) [Time frame: At 3 and 6 months after CVT diagnosis]
• Number of participants who discontinued anticoagulant therapy early [Time frame: At 6 months after CVT diagnosis]
• Number of participants with arterial thrombotic events [Time frame: At 6 months after CVT diagnosis]
• Health-related quality of life (EQ-5D-5L utility index score) [Time frame: At 3 and 6 months after CVT diagnosis]
• Serial D-dimer measurements after CVT [Time frame: At 3 and 6 months after CVT diagnosis]
• Venous recanalization [Time frame: At 6 months after CVT diagnosis]
• Frequency of chronic headache after CVT [Time frame: At 6 months after CVT diagnosis]

Eligibility criteria

Inclusion criteria

• Signed informed consent (ICF) to participate in the study
• Age ≥ 18 years
• Confirmed diagnosis of cerebral venous thrombosis (CVT) based on clinical presentation and neuroimaging, including one or more of the following:

MRI and MRV, AND/OR CT and CTV, AND/OR MRI or CT combined with DSA

• Initiation of DOACs within 5 to 15 days after starting treatment with heparin

Exclusion criteria

• CVT accompanied by antiphospholipid syndrome with all three positive laboratory criteria: lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein antibodies
• CVT in pregnant patients requiring continuous anticoagulation throughout pregnancy
• CVT with coexisting bleeding disorders, including immune thrombocytopenia with platelet count <100,000/mL, hemophilia A or B, von Willebrand disease, or a history of prolonged bleeding after surgery or invasive procedures
• CVT in patients with mechanical heart valves, atrial fibrillation, and moderate to severe mitral stenosis
• CVT in patients with a glomerular filtration rate (GFR) <15 mL/min
• CVT with severe hepatic impairment
• Patients already receiving anticoagulation therapy for another underlying condition at the time of CVT diagnosis

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Vietnam · 1 center

• Bach Mai Hospital — Hanoi

Publications

• Yang M, Rendas-Baum R, Varon SF, Kosinski M. Validation of the Headache Impact Test (HIT-6) across episodic and chronic migraine. Cephalalgia. 2011 Feb;31(3):357-67. doi: 10.1177/0333102410379890. Epub 2010 Sep 6. PMID 20819842
• Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available. PMID 29368949
• Aguiar de Sousa D, Lucas Neto L, Arauz A, Sousa AL, Gabriel D, Correia M, Gil-Gouveia R, Penas S, Carvalho Dias M, Correia MA, Carvalho M, Canhao P, Ferro JM. Early Recanalization in Patients With Cerebral Venous Thrombosis Treated With Anticoagulation. Stroke. 2020 Apr;51(4):1174-1181. doi: 10.1161/STROKEAHA.119.028532. Epub 2020 Mar 2. PMID 32114929
• Mai VQ, Sun S, Minh HV, Luo N, Giang KB, Lindholm L, Sahlen KG. An EQ-5D-5L Value Set for Vietnam. Qual Life Res. 2020 Jul;29(7):1923-1933. doi: 10.1007/s11136-020-02469-7. Epub 2020 Mar 27. PMID 32221805
• Kaatz S, Ahmad D, Spyropoulos AC, Schulman S; Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost. 2015 Nov;13(11):2119-26. doi: 10.1111/jth.13140. No abstract available. PMID 26764429
• Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x. PMID 15842354
• Field TS, Lindsay MP, Wein T, Debicki DB, Gorman J, Heran MKS, Levin LA, Lund R, Moharir M, Peeling L, Perera KS, Siegal D, Verreault S, Foley N, Martin C, Smith EE, Mountain A, Mandzia J; Canadian Stroke Best Practice Recommendations Advisory Committee, in collaboration with the Canadian Stroke Consortium. Canadian Stroke Best Practice Recommendations, 7th Edition: Cerebral Venous Thrombosis, 202 PMID 38826076
• Ulivi L, Squitieri M, Cohen H, Cowley P, Werring DJ. Cerebral venous thrombosis: a practical guide. Pract Neurol. 2020 Oct;20(5):356-367. doi: 10.1136/practneurol-2019-002415. PMID 32958591

Identifiers

NCT: NCT07083609 · DOAC-CVT-VN2025-BMH · 45-BM-HDDD · 580-QD-DHYHN

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗