Direct Oral Anticoagulants for the Treatment of Cerebral Venous Thrombosis (DOAC-CVT)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cerebral Venous Thrombosis
• Intervention / Treatment: Drug: Oral anticoagulant

• Study Type: Observational
• Enrollment (Estimated): 1300

Contacts and Locations

• Study Contact: Name: Jonathan Coutinho, MD, PhD; Phone Number: +31205669111; Email: j.coutinho@amsterdamumc.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105AZ
      • Recruiting
      • Jonathan Coutinho
      • Contact: J Coutinho, MD, PhD; Phone Number: +31205669111; Email: j.coutinho@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CVT cohort	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality Rate	All-cause mortality	Within 3, 6, and 12 months after CVT diagnosis
Number of Participants with Recurrent VTE	Symptomatic recurrent venous thromboembolism	Within 3, 6, and 12 months after CVT diagnosis
Number of Participants with Major Bleeding	According to the criteria of the International Society on Thrombosis and Haemostasis	Within 3, 6, and 12 months after CVT diagnosis
Number of Participants with Clinically Relevant Non-Major Bleeding	According to the criteria of the International Society on Thrombosis and Haemostasis	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
Modified Rankin Scale	Scale ranges from 0 to 6, with higher scores indicating worse functional outcome	At 3, 6, and 12 months after CVT diagnosis
Cerebral Venous Recanalization Rate	According to predefined criteria (see study protocol)	At 6 months after CVT diagnosis
Frequency of chronic post-CVT symptoms	Outcome added in the extension study	At 12 months after CVT diagnosis
Symptomatic recurrent VTE rate	Outcome added in the extension study	At 24 months after CVT diagnosis

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Sahlgrenska University Hospital, Sweden; University of Helsinki; University of Lisbon; Centro Hospitalar de Lisboa Central
• Investigators: Principal Investigator: Jonathan Coutinho, MD, PhD, Amsterdam UMC, location AMC

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2021
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: August 15, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Direct Oral Anticoagulants; Cerebral Venous Thrombosis; Cerebral Venous Sinus Thrombosis; Oral Anticoagulants; Vitamin K Antagonists
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Anticoagulants
• Other Study ID Numbers: DOAC-CVT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No