DOAC Versus VKA in Patients With Non-high-risk APS : Prospective Cohort Study (DOWAPS)

June 11, 2025 updated by: Virginie Dufrost, Central Hospital, Nancy, France

Direct Oral Anticoagulants Versus Warfarin in Patients With Non-high-risk Antiphospholipid Syndrome : Prospective Cohort Study

Antiphospholipid syndrome (APS) is a thrombotic disease requiring prolonged anticoagulation. Direct oral anticoagulants (DOACs) are indicated as 1st-line therapy in venous thrombosis, compared with VKAs, due to their easier handling and lower bleeding risk for equivalent efficacy. In APS, VKAs are still the reference treatment. However, DOACs are generally introduced in the acute phase of venous, before the diagnosis of APS. VKA have the disadvantage of numerous food and drug interactions, and therefore require close monitoring of INR, at least once a month. Because they are easier to use than VKAs, and the risk of bleeding is lower, patients are often reluctant to switch from DOACs to VKA. Studies have shown that APS patients with high thrombotic risk (positivity of all three antiphospholipid tests, history of arterial or small vessels thrombosis or cardiac valve damage) have an increased thrombotic risk during DOACs vs. VKA treatment. Since 2020, the ISTH guidelines have suggested avoiding DOACs in high-risk APS, but suggest continuing theim in other patients if they were introduced for venous thrombosis and if follow-up on DOACs is reassuring. In the case of high-risk APS patients, the relay is therefore systematic. For non-high-risk patients (the majority), there are no data to justify systematic switch. Given the quality-of-life advantages of DOACs over VKAs, patients are not always in favor of changing their anticoagulant therapy, especially if they have been on it for many years with good tolerability. For these reasons, a number of patients with non-high-risk APS remain on DOACs. Nevertheless, the limited data available on the efficacy of DOACs in non-high-risk patients are of low level of evidence and contradictory. In 2020, a literature review of non-high-risk SAPL patients treated with DOACs reported that 8.6% of them experienced thrombotic recurrence within 12 months, with no possible comparison with VKAs. A recent retrospective study with 96 patients reported that 15.4% of patients treated with DOACs had a recurrence, compared to 5.3% on VKAs. However, this difference was not statistically significant (p=0.15) due to a clear lack of power. The objective is to determine the frequency of thrombotic recurrences and to compare it according to the type of oral treatment, anti-Xa versus VKA, in non-high-risk APS, through a cohort study with prospective follow-up. The patient's usual antithrombotic treatment, DOAC and VKA, will be continued unchanged.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

prospective cohort of APS patient treated with VKA or DOACs (specially oral Xa treatment).

APS patients will be non high risk patients (no triple positivity, any previous arterial or small vessels thrombosis or cardiac involvment).

the treatment taken by the patient at inclusion will not be modified. There will therefore be no change to the patient's usual management.

all patients will have a blood sample taken at inclusion as part of a routine blood test.

Patients will be prospectively follow up and the level of recurrence thrombotic event will be recorded

Study Type

Observational

Enrollment (Estimated)

310

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France, 80054
        • CHU d'AMIENS
        • Principal Investigator:
          • Simon SOUDET
        • Contact:
        • Sub-Investigator:
          • Valery SALLE
      • Besançon, France, 25030
        • CHU de Besançon
        • Contact:
        • Principal Investigator:
          • Nadine MAGY BERTRAND
      • Brest, France, 29200
      • Dijon, France, 21079
        • CHU de Dijon
        • Principal Investigator:
          • Hélène GREIGERT
        • Contact:
        • Sub-Investigator:
          • Najib EL HSSAINI
      • Lyon, France, 69003
        • CHU de Lyon
        • Contact:
        • Principal Investigator:
          • Thomas BARBA
      • Metz, France, 57000
        • Hôpital Robert Schuman, UNEOS
        • Contact:
        • Principal Investigator:
          • Julien CAMPAGNE
      • Mulhouse, France, 68100
        • CH de Mulhouse
        • Contact:
        • Principal Investigator:
          • Amer HAMADE
      • Nantes, France, 44800
      • Paris, France, 75010
        • Hôpital Lariboisière - APHP
        • Contact:
        • Principal Investigator:
          • Maxime DELRUE
        • Sub-Investigator:
          • Damien SENE
      • Reims, France, 51100
        • CHU de Reims
        • Contact:
        • Principal Investigator:
          • Amélie SERVETTAZ
      • Saint-Priest En Jarez, France, 42270
      • Strasbourg, France, 67091
        • CHU de Strasbourg - Hôpital Civil
        • Principal Investigator:
          • Anne Sophie KORGANOW
        • Contact:
        • Principal Investigator:
          • Dominique STEPHAN
    • Grand Est
      • Vandoeuvre-lès-Nancy, Grand Est, France, 54500
        • Central Hospital, Nancy, France
        • Contact:
        • Contact:
        • Principal Investigator:
          • Virginie DUFROST, MD
        • Principal Investigator:
          • Thomas MOULINET, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Population of "non-high-risk" thrombotic APS patients treated with oral AntiXa or VKA regarding the treatment already taken at inclusion. Non-high-risk" APS is defined by no history of arterial or small vessels thrombosis, any valvulopathy related to APS, and a biological profile with only one or two positive antiphospholipid tests.

Patients will be recruited via the departments authorized to manage them, during their consultation or hospitalization. Patients will be invited to participate in the study as part of their regular follow-up visit. There will be no change in current antithrombotic treatment at the time of inclusion.

Description

Inclusion Criteria:

  • Persons who have received full information about the organization of the research and have given their oral consent to participate.
  • Male or female 18 years of age or older;

  • Carrier of venous thrombotic SAPL:

    • Not favoured by a major or ≥ 2 minor favouring factors, if the patient doesn't present with obstetrical SAPL in accordance with the ACR/EULAR 2023 clinical classification criteria.
    • Or favored by ≥ 2 minors, if the patient has obstetrical SAPL: severe preeclampsia < 34 weeks or placental insufficiency
    • Regardless of how long the disease has been present

    • With persistent positivity of at least one biological criterion:

      • Positivity of circulating lupus anticoagulant or IgG anticardiolipid or IgG anti-beta-2GPI
      • And persistence of the same positive test ≥ 12 weeks apart
      • And With maximum delay of positivity of the 1st antiphospholipid test of 3 years after the thrombotic event

  • Current anticoagulant treatment, regardless of date of introduction

    • rivaroxaban or apixaban
    • or antivitamin K
  • Patient affiliated to a social security system

Exclusion Criteria:

  • Venous thrombotic event motivating current anticoagulant treatment favoured by a major favouring factor:

    • Active cancer
    • Hospitalization with bed rest for at least 3 days in the 3 months preceding the event
    • Major trauma with fractures or spinal cord injury in the month preceding the event
    • Surgery with general/spinal/epidural anesthesia for > 30 minutes in the 3 months preceding the event.

  • In the absence of a history of pre-eclampsia or placental insufficiency: venous thrombotic event motivating current anticoagulant treatment favoured by 2 or more minor favouring factors:

    • Systemic autoimmune disease or active inflammatory bowel disease
    • Acute/severe infection
    • Central venous catheter in the same vascular bed
    • Hormone replacement therapy, estrogenic oral contraceptives, or hormone-stimulating therapy in progress
    • Long-distance travel (≥ 8 hours)
    • Obesity (BMI ≥ 30 kg/m²)
    • Pregnancy or post-partum (6 weeks after delivery)
    • Prolonged immobilization
    • Surgery with general/spinal/epidural anesthesia for < 30 minutes in the 3 months preceding the event
  • Known triple antiphospholipid positivity
  • Isolated IgM antiphospholipid positivity
  • History of known arterial thrombosis
  • History of known microcirculatory thrombosis
  • Known SAPL-related cardiac valvular disease
  • Persons referred to in articles L. 1121-5, L. 1121-7 and L1121-8 of the Public Health Code
  • Persons deprived of their liberty by judicial or administrative decision, persons under psychiatric care under articles L. 3212-1 and L. 3213-1.
  • Glomerular filtration rate < 30ml/min.
  • Weight < 50kg
  • History of thrombotic recurrence under well-administered anticoagulant therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patient with VKA treatment
Population of "non-high-risk" thrombotic APS patients treated with VKAs, regardless of how long they have been on therapy. "Non-high-risk" APS is defined by the absence of a history of arterial or microcirculatory thrombosis, the absence of valvulopathy related to APS and a biological profile with only one or two positive antiphospholipid tests.
Biological: Additional blood collection during routine blood sampling at the inclusion (33.9 ml) and at the thrombotic recurrence (between 3.5 and 5 ml)

At inclusion, the blood sample is used to perform thrombin generation tests (activated protein C resistance profile and ratio), classical and innovative aPL assays centrally to limit the fluctuation inherent in the tests used and enable comparison between patients, immunothrombosis markers: circulating neutrophil extracellular traps (NETs) assay, sTREM-1 assay

In the event of recurrence, blood sampling can be used to confirm compliance with treatment by measuring the anti Xa activity of the drug or INR

Behavioral: Completion of a questionnaire on compliance with anticoagulant treatment
The Girerd questionnaire (6 questions) will be proposed to patients in order to estimate the degree of compliance with AODs and VKAs at inclusion and at each follow-up visit for the duration of their participation in the study.
Other Names:
  • GIRERD questionnaire
Behavioral: Completion of a questionnaire on satisfaction with treatment anticoagulant
The ACTS questionnaire (15 questions) will be proposed to them in order to estimate their satisfaction with their anticoagulant treatment (AOD or AVK) at inclusion and at each follow-up visit for the duration of their participation in the study.
Other Names:
  • Anti-Clot Treatment Scale - ACTS
Patient with DOAC treatment
Population of "non-high-risk" thrombotic APS patients treated with oral AntiXa, regardless of how long they have been treated. Non-high-risk" APS is defined by the absence of a history of arterial or microcirculatory thrombosis, the absence of valvulopathy related to APS, and a biological profile with only one or two positive antiphospholipid tests.
Biological: Additional blood collection during routine blood sampling at the inclusion (33.9 ml) and at the thrombotic recurrence (between 3.5 and 5 ml)

At inclusion, the blood sample is used to perform thrombin generation tests (activated protein C resistance profile and ratio), classical and innovative aPL assays centrally to limit the fluctuation inherent in the tests used and enable comparison between patients, immunothrombosis markers: circulating neutrophil extracellular traps (NETs) assay, sTREM-1 assay

In the event of recurrence, blood sampling can be used to confirm compliance with treatment by measuring the anti Xa activity of the drug or INR

Behavioral: Completion of a questionnaire on compliance with anticoagulant treatment
The Girerd questionnaire (6 questions) will be proposed to patients in order to estimate the degree of compliance with AODs and VKAs at inclusion and at each follow-up visit for the duration of their participation in the study.
Other Names:
  • GIRERD questionnaire
Behavioral: Completion of a questionnaire on satisfaction with treatment anticoagulant
The ACTS questionnaire (15 questions) will be proposed to them in order to estimate their satisfaction with their anticoagulant treatment (AOD or AVK) at inclusion and at each follow-up visit for the duration of their participation in the study.
Other Names:
  • Anti-Clot Treatment Scale - ACTS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of thrombotic recurrence between the 2 arms
Time Frame: "From enrollment to the thrombotic recurrence or the end of the study (24 months post-inclusion)

Occurrence (percentage at group level) of thrombotic recurrence within 24 months of inclusion confirmed by objective examination and defined by the occurrence of one of the following events:

  • Venous thrombosis of any location or pulmonary embolism
  • Arterial thrombosis in any location
  • Microcirculatory thrombosis in any location
"From enrollment to the thrombotic recurrence or the end of the study (24 months post-inclusion)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Risk Factors of thrombotic recurrence on the 2 arms
Time Frame: Biological parameters : at the end of the study after the last visit of the last patient. No biological parameters : from enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
The risk factors for thrombotic recurrence tested were: age, gender, cardiovascular risk factors, manifestations associated with APS, associated autoimmune diseases, biological parameters (antiXa activity, INR, biomarkers of immunothrombosis collected as part of the research.
Biological parameters : at the end of the study after the last visit of the last patient. No biological parameters : from enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
Occurrence of major hemorrhage between the 2 arms
Time Frame: From enrollment to the end of follow-up (24 month post-inclusion or thrombotic recurrence)
Major bleeding as defined by the International Society on Thrombosis and Haemostasis within Haemostasis within 24 months of inclusion
From enrollment to the end of follow-up (24 month post-inclusion or thrombotic recurrence)
Occurrence of clinically relevant hemorrhage between the 2 arms
Time Frame: From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
Occurrence of clinically relevant bleeding as defined by the International Society on Thrombosis and Haemostasis within 24 months of inclusion
From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
Occurrence of a minor bleed between the 2 arms
Time Frame: From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
Occurrence of a minor bleed within 24 months of inclusion, defined as a bleed that does not meet the International Society on Thrombosis and Haemostasis definition of clinically relevant major or non-major bleeding.
From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
Net clinical benefit defined as a composite endpoint between the 2 arms
Time Frame: From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
Net clinical benefit defined as a composite endpoint including venous, arterial or microcirculatory thrombotic recurrence, cardiovascular death or major bleeding as defined by ISTH during 24-month follow-up.
From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
Drug Compliance evaluation between the 2 arms
Time Frame: From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
Drug Compliance score assessed by Girerd test at baseline and follow-up visits. Score between 0 to 6. 0 indicates a good observance, 1 to 2 : minimal observance problem and ≥ 3 : Poor compliance
From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
Quality of life under anticoagulants evaluation by Anti-Clot Treatment Scale (ACTS) satisfaction scores between the 2 arms
Time Frame: From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)

Anti-Clot Treatment Scale (ACTS) satisfaction scores measured at inclusion and at follow-up visits.

The ACTS Burdens total score ranges from 12 to 60, and the ACTS Benefits total score ranges from 3 to 15. A high score for both indicates better quality of life on anticoagulants
From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Central Hospital, Nancy, France

Investigators

  • Principal Investigator: Virginie DUFROST, MD, CHRU - Nancy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 15, 2025

Primary Completion (Estimated)

September 15, 2031

Study Completion (Estimated)

September 15, 2031

Study Registration Dates

First Submitted

March 13, 2025

First Submitted That Met QC Criteria

March 13, 2025

First Posted (Actual)

March 19, 2025

Study Record Updates

Last Update Posted (Actual)

June 13, 2025

Last Update Submitted That Met QC Criteria

June 11, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-A02295-42
  • 2023-0195 (Other Identifier: Promotor code)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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