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

NCT06884384 | Not Yet Recruiting

• 2 other identifiers: 2024-A02295-422023-0195
• Study Type: observational
• Target: 310
• Locations: 1 country
• Sites: 13

Brief 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. 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.

Conditions

Antiphospholipid Syndrome (APS); Cohort Study; Thrombotic and Bleeding Events

Keywords

Antiphospholipid Syndrome; VKA treatment; DOAC Treatment; biological analysis; Thrombotic and bleeding events

Outcome Measures

Primary Outcomes (1)

• 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

  "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

  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

  From enrollment to the end of follow-up (24 month post-inclusion or thrombotic recurrence)

• Occurrence of clinically relevant hemorrhage between the 2 arms

  From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)

• Occurrence of a minor bleed between the 2 arms

  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

  From enrollment to the end of follow-up (24 months post-inclusion or thrombotic recurrence)

Study Arms (2)

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); 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.

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

Interventions

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

Patient with DOAC treatment; Patient with VKA treatment

Completion of a questionnaire on compliance with anticoagulant treatment BEHAVIORAL

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.

Also known as: GIRERD questionnaire

Patient with DOAC treatment; Patient with VKA treatment

Completion of a questionnaire on satisfaction with treatment anticoagulant BEHAVIORAL

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.

Also known as: Anti-Clot Treatment Scale - ACTS

Patient with DOAC treatment; Patient with VKA treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (13)

Central Hospital, Nancy, France

Vandœuvre-lès-Nancy, Grand Est, 54500, France

Location

CHU d'Amiens

Amiens, 80054, France

Location

CHU de Besançon

Besançon, 25030, France

Location

CHU de Brest

Brest, 29200, France

Location

CHU de Dijon

Dijon, 21079, France

Location

CHU de Lyon

Lyon, 69003, France

Location

Hôpital Robert Schuman, UNEOS

Metz, 57000, France

Location

CH de Mulhouse

Mulhouse, 68100, France

Location

CHU de Nantes

Nantes, 44800, France

Location

Hôpital Lariboisière - APHP

Paris, 75010, France

Location

CHU de Reims

Reims, 51100, France

Location

CHU de Saint Etienne

Saint-Priest-en-Jarez, 42270, France

Location

CHU de Strasbourg - Hôpital civil

Strasbourg, 67091, France

Location

Related Publications (5)

• 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.

  PMID: 34817786 BACKGROUND

• Dufrost 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.

  PMID: 32436109 BACKGROUND

• Zuily 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.

  PMID: 32881337 BACKGROUND

• Dufrost 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.

  PMID: 30103045 BACKGROUND

• Pengo 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.

  PMID: 30002145 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

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

MeSH Terms

Conditions

Antiphospholipid Syndrome

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases

Study Officials

• Virginie DUFROST, MD

  CHRU - Nancy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 13, 2025
• First Posted: March 19, 2025
• Study Start: September 15, 2025
• Primary Completion (Estimated): September 15, 2031
• Study Completion (Estimated): September 15, 2031
• Last Updated: June 13, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (13)