Clinical trial NCT04660747: Direct Oral Anticoagulants for the Treatment of Cerebral Venous Thrombosis
Official title: Direct Oral Anticoagulants for the Treatment of Cerebral Venous Thrombosis: An International Phase IV Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cerebral Venous Thrombosis
Keywords: Cerebral Venous Thrombosis
Cerebral Venous Sinus Thrombosis
Oral Anticoagulants
Direct Oral Anticoagulants
Vitamin K Antagonists
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: University of Lisbon
name: Sahlgrenska University Hospital
name: University of Helsinki
name: Centro Hospitalar de Lisboa Central
First posted: 2020-12-09
Enrollment: 1300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Composite Outcome: Number of Participants with Major Bleeding and Recurrent VTE
timeFrame: Within 6 months after CVT diagnosis
Secondary outcomes:
measure: Mortality Rate
timeFrame: Within 3, 6, and 12 months after CVT diagnosis
measure: Number of Participants with Recurrent VTE
timeFrame: Within 3, 6, and 12 months after CVT diagnosis
measure: Number of Participants with Major Bleeding
timeFrame: Within 3, 6, and 12 months after CVT diagnosis
measure: Number of Participants with Clinically Relevant Non-Major Bleeding
timeFrame: Within 3, 6, and 12 months after CVT diagnosis
measure: Number of Participants with Arterial Thrombotic Event
timeFrame: Within 3, 6, and 12 months after CVT diagnosis
measure: Modified Rankin Scale
timeFrame: At 3, 6, and 12 months after CVT diagnosis
measure: Cerebral Venous Recanalization Rate
timeFrame: At 6 months after CVT diagnosis
measure: Frequency of chronic post-CVT symptoms
timeFrame: At 12 months after CVT diagnosis
measure: Symptomatic recurrent VTE rate
timeFrame: At 24 months after CVT diagnosis
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Jonathan Coutinho
state: Noord-Holland
Study officials:
affiliation: Amsterdam UMC, location AMC
name: Jonathan Coutinho, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: