Cerebral Venous ThrombosisDOAC-CVTNCT04660747
Direct Oral Anticoagulants for the Treatment of Cerebral Venous Thrombosis
An observational study of Cerebral Venous Thrombosis, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cerebral Venous Thrombosis
- What is being tested?
- Oral anticoagulant
- Type of treatment
- Pill or oral medicine
- How many people
- 1,300 participants
- Where
- 1 siteNetherlands
- Study dates
- 27 Jan 2021to Jan 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Jonathan Coutinho
Amsterdam, North Holland, 1105AZ
J Coutinho, MD, PhD, +31205669111, j.coutinho@amsterdamumc.nl
About this study
Official title: 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.
Read more
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.
- Conditions
- Cerebral Venous Thrombosis
- Being tested
- Oral anticoagulant
- Keywords
- Cerebral Venous Thrombosis, Cerebral Venous Sinus Thrombosis, Oral Anticoagulants, Direct Oral Anticoagulants, Vitamin K Antagonists
- Medical subject headings
- Intracranial Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral anticoagulantDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| CVT cohort | Not described Receives: Drug: Oral anticoagulant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Within 6 months after CVT diagnosis
Secondary outcomes (9)
Mortality Rate
All-cause mortality
Measured: Within 3, 6, and 12 months after CVT diagnosis
Number of Participants with Recurrent VTE
Symptomatic recurrent venous thromboembolism
Measured: 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
Measured: 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
Measured: Within 3, 6, and 12 months after CVT diagnosis
Number of Participants with Arterial Thrombotic Event
Measured: 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
Measured: At 3, 6, and 12 months after CVT diagnosis
Cerebral Venous Recanalization Rate
According to predefined criteria (see study protocol)
Measured: At 6 months after CVT diagnosis
Frequency of chronic post-CVT symptoms
Outcome added in the extension study
Measured: At 12 months after CVT diagnosis
Symptomatic recurrent VTE rate
Outcome added in the extension study
Measured: At 24 months after CVT diagnosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2020
- Study start27 Jan 2021
- Primary completionAug 2024 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cerebral Venous ThrombosisStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,300 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- University of Lisbon, Sahlgrenska University Hospital, University of Helsinki, Centro Hospitalar de Lisboa Central
- Responsible party
- Principal investigator, Jonathan Coutinho, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Jonathan Coutinho, MD, PhD, Principal investigator, Amsterdam UMC, location AMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04660747
- Sponsor's protocol ID
- DOAC-CVT
- Acronym
- DOAC-CVT
- Status last verified
- Aug 2024
- First submitted
- 3 Dec 2020
- Last updated
- 19 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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, Miraclin A, Rani LJ, Reddy YM, Saleem S, Scutelnic A, Shanmugasundaram S, van den Wijngaard IR, Gencdal IY, van Eekelen R, Vellema J, Arnold M, Neto L, Middeldorp S, de Sousa DA, Jood K, Putaala J, Ferro JM, Coutinho JM; DOAC-CVT investigators. Direct oral anticoagulants versus vitamin K antagonists for cerebral venous thrombosis (DOAC-CVT): an international, prospective, observational cohort study. Lancet Neurol. 2025 Mar;24(3):199-207. doi: 10.1016/S1474-4422(24)00519-2.
PubMed 39986309van 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 anticoagulants for the treatment of cerebral venous thrombosis - a protocol of an international phase IV study. Front Neurol. 2023 Sep 14;14:1251581. doi: 10.3389/fneur.2023.1251581. eCollection 2023.
PubMed 37780701
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Direct Oral Anticoagulants for the Treatment of Cerebral Venous Thrombosis: An International Phase IV Study
- ClinicalTrials.gov ID
- NCT04660747
- Acronym / sponsor ID
- DOAC-CVT / DOAC-CVT
- Conditions
- Cerebral Venous Thrombosis
- Keywords
- Cerebral Venous Thrombosis, Cerebral Venous Sinus Thrombosis, Oral Anticoagulants, Direct Oral Anticoagulants, Vitamin K Antagonists
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,300 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- University of Lisbon, Sahlgrenska University Hospital, University of Helsinki, Centro Hospitalar de Lisboa Central
- Study start
- 27 Jan 2021 (actual)
- Primary completion
- Aug 2024 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 9 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CVT cohort | – | Drug: Oral anticoagulant |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral anticoagulantDirect 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. | Drug | CVT cohort |
Primary outcome
Composite Outcome: Number of Participants with Major Bleeding and Recurrent VTE
Time frame: 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
9 secondary outcomes
Mortality Rate
Time frame: Within 3, 6, and 12 months after CVT diagnosis
Number of Participants with Recurrent VTE
Time frame: Within 3, 6, and 12 months after CVT diagnosis
Number of Participants with Major Bleeding
Time frame: Within 3, 6, and 12 months after CVT diagnosis
Number of Participants with Clinically Relevant Non-Major Bleeding
Time frame: Within 3, 6, and 12 months after CVT diagnosis
Number of Participants with Arterial Thrombotic Event
Time frame: Within 3, 6, and 12 months after CVT diagnosis
Modified Rankin Scale
Time frame: At 3, 6, and 12 months after CVT diagnosis
Cerebral Venous Recanalization Rate
Time frame: At 6 months after CVT diagnosis
Frequency of chronic post-CVT symptoms
Time frame: At 12 months after CVT diagnosis
Symptomatic recurrent VTE rate
Time frame: At 24 months after CVT diagnosis
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2024.
- Derived from this study: PubMed 39986309van 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, Miraclin A, Rani LJ, Reddy YM, Saleem S, Scutelnic A, Shanmugasundaram S, van den Wijngaard IR, Gencdal IY, van Eekelen R, Vellema J, Arnold M, Neto L, Middeldorp S, de Sousa DA, Jood K, Putaala J, Ferro JM, Coutinho JM; DOAC-CVT investigators. Direct oral anticoagulants versus vitamin K antagonists for cerebral venous thrombosis (DOAC-CVT): an international, prospective, observational cohort study. Lancet Neurol. 2025 Mar;24(3):199-207. doi: 10.1016/S1474-4422(24)00519-2.
- Derived from this study: PubMed 37780701van 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 anticoagulants for the treatment of cerebral venous thrombosis - a protocol of an international phase IV study. Front Neurol. 2023 Sep 14;14:1251581. doi: 10.3389/fneur.2023.1251581. eCollection 2023.
Related trials for Cerebral Venous Thrombosis
RecruitingObservational study
Danang Cerebral Venous Thrombosis Registry
Cerebral Venous Sinus Thrombosis, Stroke
Not yet recruitingObservational study
TOF-MRV Versus Post-Contrast 3D T1 MRI in Dural Venous Sinus Thrombosis
Cerebral Thrombosis, Venous Thrombosis
Recruiting
MENA Regional Endovascular Intervention for Venous Cerebral Venous Sinus Thrombosis
Cerebral Venous Sinus Thrombosis
RecruitingPhase 3
Stroke and Systemic Embolism Prevention in Adult Participants With Atrial Fibrillation for Whom Oral Anticoagulation is Unsuitable
Atrial Fibrillation (AF)
RecruitingObservational study
Treatment Outcomes of Direct Oral Anticoagulants in Cerebral Venous Thrombosis in Vietnam
Cerebral Venous Thrombosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jonathan Coutinho, MD, PhD principal investigator
Amsterdam UMC, location AMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cerebral Venous Thrombosis, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jonathan Coutinho, MD, PhD (+31205669111, j.coutinho@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Outcome: Number of Participants with Major Bleeding and Recurrent VTE (time frame: Within 6 months after CVT diagnosis). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04660747, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2024.