Direct Oral Anticoagulants for the Treatment of Cerebral Venous Thrombosis

Официальное название

Direct Oral Anticoagulants for the Treatment of Cerebral Venous Thrombosis: An International Phase IV Study

Обзор

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.

Вмешательства

• Препарат Oral anticoagulant
  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.

Первичные конечные точки

• Composite Outcome: Number of Participants with Major Bleeding and Recurrent VTE [Срок оценки: Within 6 months after CVT diagnosis]

Вторичные конечные точки (9)

• Mortality Rate [Срок оценки: Within 3, 6, and 12 months after CVT diagnosis]
• Number of Participants with Recurrent VTE [Срок оценки: Within 3, 6, and 12 months after CVT diagnosis]
• Number of Participants with Major Bleeding [Срок оценки: Within 3, 6, and 12 months after CVT diagnosis]
• Number of Participants with Clinically Relevant Non-Major Bleeding [Срок оценки: Within 3, 6, and 12 months after CVT diagnosis]
• Number of Participants with Arterial Thrombotic Event [Срок оценки: Within 3, 6, and 12 months after CVT diagnosis]
• Modified Rankin Scale [Срок оценки: At 3, 6, and 12 months after CVT diagnosis]
• Cerebral Venous Recanalization Rate [Срок оценки: At 6 months after CVT diagnosis]
• Frequency of chronic post-CVT symptoms [Срок оценки: At 12 months after CVT diagnosis]
• Symptomatic recurrent VTE rate [Срок оценки: At 24 months after CVT diagnosis]

Критерии участия

Критерии включения

• 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)
• Inclusion in the study within 90 days of CVT diagnosis

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Нидерланды · 1 центр

• Jonathan Coutinho — Amsterdam

Публикации

• 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, PMID 39986309
• 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 anti PMID 37780701

Идентификаторы

NCT: NCT04660747 · DOAC-CVT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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