Direct Oral Anticoagulants for the Treatment of Cerebral Venous Thrombosis

Recruiting

• Conditions: Cerebral Venous Thrombosis
• Interventions: Drug: Oral anticoagulant

• Registration Number: NCT04660747
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-12-03
• Study First Submitted QC: 2020-12-03
• Study First Posted: 2020-12-09
• Study Start: 2021-01-27
• Status Verified: 2024-08
• Primary Completion: 2024-08
• Last Update Submitted: 2024-08-15
• Last Update Posted: 2024-08-19
• Study Completion: 2028-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1300

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
CVT cohort	Oral anticoagulant	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Number of Participants with Recurrent VTE	Within 3, 6, and 12 months after CVT diagnosis	Symptomatic recurrent venous thromboembolism
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
Cerebral Venous Recanalization Rate	At 6 months after CVT diagnosis	According to predefined criteria (see study protocol)
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
Frequency of chronic post-CVT symptoms	At 12 months after CVT diagnosis	Outcome added in the extension study
Mortality Rate	Within 3, 6, and 12 months after CVT diagnosis	All-cause mortality
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 Arterial Thrombotic Event	Within 3, 6, and 12 months after CVT diagnosis
Symptomatic recurrent VTE rate	At 24 months after CVT diagnosis	Outcome added in the extension study

Trial Locations

Locations (1)

Jonathan Coutinho; 🇳🇱 Amsterdam, Noord-Holland, Netherlands