Cerebral Venous Thrombosis
Conditions
Keywords
Cerebral Venous Thrombosis, Cerebral Venous Sinus Thrombosis, Oral Anticoagulants, Direct Oral Anticoagulants, Vitamin K Antagonists
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.
Interventions
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.
Sponsors
University of Lisbon
Sahlgrenska University Hospital
University of Helsinki
Centro Hospitalar de Lisboa Central
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Outcome: Number of Participants with Major Bleeding and Recurrent VTE | Within 6 months after CVT diagnosis | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Recurrent VTE | Within 3, 6, and 12 months after CVT diagnosis | Symptomatic recurrent venous thromboembolism |
| Number of Participants with Major Bleeding | Within 3, 6, and 12 months after CVT diagnosis | According to the criteria of the International Society on Thrombosis and Haemostasis |
| Number of Participants with Clinically Relevant Non-Major Bleeding | Within 3, 6, and 12 months after CVT diagnosis | According to the criteria of the International Society on Thrombosis and Haemostasis |
| Number of Participants with Arterial Thrombotic Event | Within 3, 6, and 12 months after CVT diagnosis | — |
| Mortality Rate | Within 3, 6, and 12 months after CVT diagnosis | All-cause mortality |
| Cerebral Venous Recanalization Rate | At 6 months after CVT diagnosis | According to predefined criteria (see study protocol) |
| Frequency of chronic post-CVT symptoms | At 12 months after CVT diagnosis | Outcome added in the extension study |
| Symptomatic recurrent VTE rate | At 24 months after CVT diagnosis | Outcome added in the extension study |
| Modified Rankin Scale | At 3, 6, and 12 months after CVT diagnosis | Scale ranges from 0 to 6, with higher scores indicating worse functional outcome |
Countries
Netherlands
Contacts
Primary ContactJonathan Coutinho, MD, PhD
Outcome results
None listed