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

Central Hospital, Nancy, France

Status: Not yet enrolling

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

Treatments: Behavioral: Completion of a questionnaire on satisfaction with treatment anticoagulant; 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

Study type: Observational

Funder types: Other

Identifiers

NCT06884384

2023-0195 (Other Identifier)

2024-A02295-42

Details and patient eligibility

About

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.

Full 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

Enrollment: 310 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

310 participants in 2 patient groups

Patient with VKA treatment

Description:

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.

Treatment:

Behavioral: Completion of a questionnaire on compliance with anticoagulant treatment

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 satisfaction with treatment anticoagulant

Patient with DOAC treatment

Description:

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.

Treatment:

Behavioral: Completion of a questionnaire on compliance with anticoagulant treatment

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 satisfaction with treatment anticoagulant