Direct Oral Anticoagulants for the Treatment of Cerebral Venous Thrombosis

NCT04660747 | Recruiting

• 1 other identifier: DOAC-CVT
• Study Type: observational
• Target: 1,300
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Patients with cerebral venous thrombosis (CVT) are currently treated with anticoagulants during 3-12 months after diagnosis, to prevent worsening of the CVT and recurrent thrombosis, and to promote venous recanalization. Until recently, patients were generally treated with vitamin K antagonists (VKA). Direct oral anticoagulants (DOACs) are more practical in use than VKA and carry a lower risk of intracranial hemorrhage (ICH) in other conditions. One of the burning clinical questions is whether CVT patients can be safely treated with DOACs instead of VKA. In 2019, the first randomized trial on the safety and efficacy of DOACs in CVT was published (RESPECT-CVT). This exploratory study included 120 patients and the results suggest that DOACs can be safely used to treat CVT. Following RESPECT-CVT, use of DOACs to treat CVT is expected to rise, but given the limited sample size and strict selection criteria of RESPECT-CVT, additional data regarding the efficacy and safety of DOACs in CVT are required, especially from routine clinical care. Objective: To assess the safety and efficacy of DOACs for the treatment of CVT in a real-world setting. Study design: DOAC-CVT is an international, prospective, comparative cohort study. Initially, DOAC-CVT was designed to recruit 500 patients in a three-year study period. All patients recruited until January 15, 2024 will be included in the primary data analysis as previously described (https://doi.org/10.3389/fneur.2023.1251581). In addition, we will continue patient recruitment in an extension of the study until January 2026 to have a larger sample size, add new research questions, and to further strengthen global. We aim to recruit 1300 patients and anticipating a 3:2 ratio in DOAC:VKA use, we expect that in total 780 patients treated with a DOAC will be included. Study population: Patients are eligible if they are \>18 years old, have a radiologically confirmed CVT, have started oral anticoagulant treatment (DOAC or VKA) within 30 days of CVT diagnosis, and are included in the study within 90 days after CVT diagnosis. Primary study endpoint: The primary endpoint is a composite of major bleeding (according to the criteria of the International Society on Thrombosis and Haemostasis) AND symptomatic recurrent venous thrombosis after 6 months of follow-up. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This is an observational study which poses no risk or burden to the participant. Only data that are collected as part of routine clinical care will be used.

Conditions

Cerebral Venous Thrombosis

Keywords

Cerebral Venous Thrombosis; Cerebral Venous Sinus Thrombosis; Oral Anticoagulants; Direct Oral Anticoagulants; Vitamin K Antagonists

Outcome Measures

Primary Outcomes (1)

• Composite Outcome: Number of Participants with Major Bleeding and Recurrent VTE

  Major bleeding is defined according to the criteria of the International Society on Thrombosis and Haemostasis. Recurrent VTE is defined as symptomatic recurrent venous thromboembolism

  Within 6 months after CVT diagnosis

Secondary Outcomes (9)

• Mortality Rate

  Within 3, 6, and 12 months after CVT diagnosis

• Number of Participants with Recurrent VTE

  Within 3, 6, and 12 months after CVT diagnosis

• Number of Participants with Major Bleeding

  Within 3, 6, and 12 months after CVT diagnosis

• Number of Participants with Clinically Relevant Non-Major Bleeding

  Within 3, 6, and 12 months after CVT diagnosis

• Number of Participants with Arterial Thrombotic Event

  Within 3, 6, and 12 months after CVT diagnosis

Study Arms (1)

CVT cohort

Drug: Oral anticoagulant

Interventions

Oral anticoagulant DRUG

Direct oral anticoagulants or vitamin K antagonists. Please note that the study is fully observational. The choice of anticoagulant type and duration of treatment are left at the discretion of the treating physicians and patients. No treatment, intervention, or examinations are imposed on patients in the context of this study.

CVT cohort

Eligibility Criteria

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

Study Population

Consecutive patients with CVT treated at the participating centres. Both patients who are admitted to the hospital and patients who are treated via outpatient clinic are eligible. Centers participating in the DOAC-CVT study keep a log of all patients with CVT presented at their hospital during the study period to register which patients were included in the study and which patients were not eligible for inclusion in the study.

You may qualify if:

• Written informed consent for the use of observational data
• Age \>18 years at the time of CVT diagnosis
• Radiologically confirmed CVT diagnosis (CT-venography, MRI or catheter angiography)
• Oral anticoagulant treatment (DOAC or VKA) started within 30 days of CVT diagnosis (patient may initially be treated with heparin)

You may not qualify if:

• Anticoagulant treatment at the time of CVT diagnosis
• Pregnancy or lactation (post-partum women are eligible if they do not give breast-feeding)
• Mechanical heart valve
• Severe renal insufficiency (defined as an eGFR \<15 ml/min)
• Severe liver disease resulting in clinically relevant coagulopathy

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• University of Lisbon: collaborator
• Sahlgrenska University Hospital: collaborator
• University of Helsinki: collaborator
• Centro Hospitalar de Lisboa Central: collaborator

Study Sites (1)

Jonathan Coutinho

Amsterdam, North Holland, 1105AZ, Netherlands

RECRUITING

Related Publications (2)

• van de Munckhof A, van Kammen MS, Tatlisumak T, Krzywicka K, Aaron S, Antochi F, Arauz A, Barboza MA, Conforto AB, Contreras DG, Heldner MR, Hernandez-Perez M, Hiltunen S, Ji X, Kam W, Kleinig TJ, Kristoffersen ES, Leker RR, Lemmens R, Poli S, Wasay M, Wu T, Yesilot N, Chen J, Cotelli MS, Demeestere J, Duan J, Ergin N, Freitas TE, Gomes A, den Hertog HM, Lindgren E, Martinez-Majander N, Metanis I, Miraclin A, Rani LJ, Reddy YM, Saleem S, Scutelnic A, Shanmugasundaram S, van den Wijngaard IR, Gencdal IY, van Eekelen R, Vellema J, Arnold M, Neto L, Middeldorp S, de Sousa DA, Jood K, Putaala J, Ferro JM, Coutinho JM; DOAC-CVT investigators. Direct oral anticoagulants versus vitamin K antagonists for cerebral venous thrombosis (DOAC-CVT): an international, prospective, observational cohort study. Lancet Neurol. 2025 Mar;24(3):199-207. doi: 10.1016/S1474-4422(24)00519-2.

  PMID: 39986309 DERIVED

• van de Munckhof A, Sanchez van Kammen M, Krzywicka K, Aaron S, Aguiar de Sousa D, Antochi F, Arauz A, Barboza MA, Conforto AB, Dentali F, Galdames Contreras D, Ji X, Jood K, Heldner MR, Hernandez-Perez M, Kam W, Kleinig TJ, Kristoffersen ES, Leker RR, Lemmens R, Poli S, Yesilot N, Wasay M, Wu TY, Arnold M, Lucas-Neto L, Middeldorp S, Putaala J, Tatlisumak T, Ferro JM, Coutinho JM. Direct oral anticoagulants for the treatment of cerebral venous thrombosis - a protocol of an international phase IV study. Front Neurol. 2023 Sep 14;14:1251581. doi: 10.3389/fneur.2023.1251581. eCollection 2023.

  PMID: 37780701 DERIVED

MeSH Terms

Conditions

Intracranial Thrombosis

Interventions

Anticoagulants

Condition Hierarchy (Ancestors)

Intracranial Embolism and Thrombosis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Thromboembolism; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

Hematologic Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Jonathan Coutinho, MD, PhD

  Amsterdam UMC, location AMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonathan Coutinho, MD, PhD

CONTACT

+31205669111; j.coutinho@amsterdamumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 9, 2020
• Study Start: January 27, 2021
• Primary Completion: August 1, 2024
• Study Completion (Estimated): January 1, 2028
• Last Updated: August 19, 2024

Record last verified: 2024-08

Locations

NL (1)