Antiphospholipid Syndrome (APS)DOWAPSNCT06884384
DOAC Versus VKA in Patients With Non-high-risk APS : Prospective Cohort Study
An observational study of Antiphospholipid Syndrome (APS) and Cohort Study, run by Central Hospital, Nancy, France at 13 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antiphospholipid Syndrome (APS), Cohort Study, Thrombotic and Bleeding Events
- What is being tested?
- Additional blood collection during routine blood sampling at the inclusion (33.9 ml) and at the thrombotic recurrence (between 3.5 and 5 ml), Completion of a questionnaire on compliance with anticoagulant treatment and Completion of a questionnaire on satisfaction with treatment anticoagulant
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- How many people
- 310 participants
- Where
- 13 sitesFrance
- Study dates
- 15 Sep 2025to 15 Sep 2031
- Phase
- Observational
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: 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.
Who may be able to join
- 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
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- 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
Who cannot join
- 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:
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- 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.
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
France13 sites
CHU d'Amiens
Amiens, 80054
Simon Soudet, 000000000, Soudet.Simon@chu-amiens.fr
Simon SOUDET
CHU de Besançon
Besançon, 25030
Nadine Magy-Bertrand, 00000000, nadine.magy@univ-fcomte.fr
Nadine MAGY BERTRAND
CHU de Brest
Brest, 29200
Francis Couturaud, 00000000, francis.couturaud@chu-brest.fr
Francis COUTURAUD
CHU de Dijon
Dijon, 21079
Hélène Greigert, MD, 00000000 ext. +33, helene.greigert@chu-dijon.fr
Hélène GREIGERT
CHU de Lyon
Lyon, 69003
Thomas Barba, 00000000, thomas.barba@chu-lyon.fr
Thomas BARBA
Hôpital Robert Schuman, UNEOS
Metz, 57000
Julien Campagne, 00000000 ext. +33, julien.campagne@uneos.fr
Julien CAMPAGNE
CH de Mulhouse
Mulhouse, 68100
Amer Hamade, 00000000, HAMADEA@ghrmsa.fr
Amer HAMADE
CHU de Nantes
Nantes, 44800
Olivier Espitia, 00000000, Olivier.ESPITIA@chu-nantes.fr
Olivier ESPITIA
Hôpital Lariboisière - APHP
Paris, 75010
Maxime Delrue, 00000000, maxime.delrue@aphp.fr
Maxime DELRUE
CHU de Reims
Reims, 51100
Amélie Servettaz, 000000000, aservettaz@chu-reims.fr
Amélie SERVETTAZ
CHU de Saint Etienne
Saint-Priest-en-Jarez, 42270
Géraldine Poenou, 00000000, Geraldine.Poenou@chu-st-etienne.fr
Géraldine POENOU
CHU de Strasbourg - Hôpital civil
Strasbourg, 67091
Dominique Stephan, 00000000, Dominique.Stephan@chru-strasbourg.fr
Dominique STEPHAN
Central Hospital, Nancy, France
Vandœuvre-lès-Nancy, Grand Est, 54500
Virginie DUFROST, MD, 0383157828 ext. +33, v.dufrost@chru-nancy.fr
Denis WAHL, MD, PhD, d.wahl@chru-nancy.fr
About this study
Official title: 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.
Read the 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
- Being tested
- Additional blood collection during routine blood sampling at the inclusion (33.9 ml) and at the thrombotic recurrence (between 3.5 and 5 ml), Completion of a questionnaire on compliance with anticoagulant treatment, Completion of a questionnaire on satisfaction with treatment anticoagulant
- Keywords
- Antiphospholipid Syndrome, VKA treatment, DOAC Treatment, biological analysis, Thrombotic and bleeding events
- Medical subject headings
- Antiphospholipid Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Additional blood collection during routine blood sampling at the inclusion (33.9 ml) and at the thrombotic recurrence (between 3.5 and 5 ml)Biological
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
Completion of a questionnaire on compliance with anticoagulant treatmentBehavioural
Also called GIRERD questionnaire
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.
Completion of a questionnaire on satisfaction with treatment anticoagulantBehavioural
Also called Anti-Clot Treatment Scale - ACTS
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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); Behavioral: Completion of a questionnaire on compliance with anticoagulant treatment; Behavioral: Completion of a questionnaire on satisfaction with treatment anticoagulant | |
| 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. Receives: 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); Behavioral: Completion of a questionnaire on compliance with anticoagulant treatment; Behavioral: Completion of a questionnaire on satisfaction with treatment anticoagulant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of thrombotic recurrence between the 2 arms
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
Measured: "From enrollment to the thrombotic recurrence or the end of the study (24 months post-inclusion)
Secondary outcomes (7)
Risk Factors of thrombotic recurrence on the 2 arms
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.
Measured: 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
Major bleeding as defined by the International Society on Thrombosis and Haemostasis within Haemostasis within 24 months of inclusion
Measured: From enrollment to the end of follow-up (24 month post-inclusion or thrombotic recurrence)
Occurrence of clinically relevant hemorrhage between the 2 arms
Occurrence of clinically relevant bleeding as defined by the International Society on Thrombosis and Haemostasis within 24 months of inclusion
Measured: From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
Occurrence of a minor bleed between the 2 arms
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.
Measured: 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
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.
Measured: From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
Drug Compliance evaluation between the 2 arms
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
Measured: 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
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
Measured: From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2025
- Study start15 Sep 2025 (estimated)
- Primary completion15 Sep 2031 (estimated)
- Study completion15 Sep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Antiphospholipid Syndrome (APS)Studies of the same condition, open and under way.
- 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
- 310 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Virginie Dufrost, Central Hospital, Nancy, France
- Investigators
- Virginie DUFROST, MD, Principal investigator, CHRU - Nancy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06884384
- Sponsor's protocol ID
- 2024-A02295-42
- Other IDs
- 2023-0195
- Acronym
- DOWAPS
- Status last verified
- Apr 2025
- First submitted
- 13 Mar 2025
- Last updated
- 13 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Williams B, Saseen JJ, Trujillo T, Palkimas S. Direct oral anticoagulants versus warfarin in patients with single or double antibody-positive antiphospholipid syndrome. J Thromb Thrombolysis. 2022 Jul;54(1):67-73. doi: 10.1007/s11239-021-02587-0. Epub 2021 Nov 24.
PubMed 34817786Dufrost V, Darnige L, Reshetnyak T, Vorobyeva M, Jiang X, Yan XX, Gerotziafas G, Jing ZC, Elalamy I, Wahl D, Zuily S. New Insights into the Use of Direct Oral Anticoagulants in Non-high Risk Thrombotic APS Patients: Literature Review and Subgroup Analysis from a Meta-analysis. Curr Rheumatol Rep. 2020 May 20;22(7):25. doi: 10.1007/s11926-020-00901-y.
PubMed 32436109Zuily S, Cohen H, Isenberg D, Woller SC, Crowther M, Dufrost V, Wahl D, Dore CJ, Cuker A, Carrier M, Pengo V, Devreese KMJ. Use of direct oral anticoagulants in patients with thrombotic antiphospholipid syndrome: Guidance from the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2020 Sep;18(9):2126-2137. doi: 10.1111/jth.14935.
PubMed 32881337Dufrost V, Risse J, Reshetnyak T, Satybaldyeva M, Du Y, Yan XX, Salta S, Gerotziafas G, Jing ZC, Elalamy I, Wahl D, Zuily S. Increased risk of thrombosis in antiphospholipid syndrome patients treated with direct oral anticoagulants. Results from an international patient-level data meta-analysis. Autoimmun Rev. 2018 Oct;17(10):1011-1021. doi: 10.1016/j.autrev.2018.04.009. Epub 2018 Aug 11.
PubMed 30103045Pengo V, Denas G, Zoppellaro G, Jose SP, Hoxha A, Ruffatti A, Andreoli L, Tincani A, Cenci C, Prisco D, Fierro T, Gresele P, Cafolla A, De Micheli V, Ghirarduzzi A, Tosetto A, Falanga A, Martinelli I, Testa S, Barcellona D, Gerosa M, Banzato A. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018 Sep 27;132(13):1365-1371. doi: 10.1182/blood-2018-04-848333. Epub 2018 Jul 12.
PubMed 30002145