A Phase 3 interventional study of Vitamin K Antagonist - Drug and Anticoagulant Therapy Discontinuation in Antiphospholipid Syndrome, Thrombotic Antiphospholipid Syndrome and Thrombosis, sponsored by Assistance Publique - Hôpitaux de Paris. Not yet recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-15.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 3, Interventional, and Treatment
This is an open-label, non-inferiority, randomized controlled trial with two parallel arms (experimental and control), following a PROBE (Prospective Randomized Open, Blinded Endpoint) design. The study evaluates whether anticoagulation cessation is non-inferior to anticoagulation maintenance regarding the risk of recurrent thrombosis after antiphospholipid antibodies (aPL) loss in patients with thrombotic antiphospholipid syndrome (APS). Currently, the cornerstone of APS treatment is long-term anticoagulation by vitamin K antagonists (VKAs), which expose patients to the risk of bleeding and have a negative impact on health-related quality of life due to the need for frequent International Normalized Ratio (INR) monitoring. No clinical trial in the existing literature has evaluated anticoagulant cessation after aPL loss. The primary endpoint is the first recurrent thrombotic event during follow-up.
The most frequent clinical manifestations of antiphospholipid syndrome (APS) are thrombotic events. The specificities of antiphospholipid antibodies (aPL), their isotypes, and the presence of multiple aPL autoantibodies have been associated with different risk profiles regarding thrombotic manifestations, while the risk of thrombotic events after disappearance of aPL appears to decrease. Currently, no clinical trial in the existing literature has evaluated anticoagulant cessation after aPL loss.
At the randomisation visit, demographic, medical, and biological characteristics are collected and the 36-Item Short Form Health Survey (SF-36) questionnaire is completed. Follow-up visits are scheduled every 3 months for the first 6 months (M3, M6), then every 6 months for a minimum of 18 months and a maximum of 42 months (M12 through M48). In the experimental arm, International Normalized Ratio (INR) testing is performed at baseline then discontinued; in the control arm, INR is monitored at baseline, at each protocol visit, in case of recurrent thrombotic event, and as clinically indicated. Serum and plasma samples are collected at baseline, at each follow-up visit, and in case of recurrent thrombotic event, for centralized aPL antibody measurement and biocollection.
The study was designed to demonstrate non-inferiority based on a 2-year outcome rate of 20% in the anticoagulant cessation group and 17% in the anticoagulation maintenance group. A total of 234 patients is required to reject the non-inferiority null hypothesis with 80% power, a one-sided type I error rate of 2.5%, and a non-inferiority margin of 10%. The primary endpoint will be analyzed in both intention-to-treat (ITT, primary analysis) and per-protocol (PP) populations. Between-group comparisons will use an appropriate statistical model (e.g., logistic regression, linear models, or Cox proportional hazards models), with treatment effect estimated together with its two-sided 95% confidence interval. Sensitivity analyses will be conducted to assess the robustness of the primary results, and missing data will be handled according to prespecified methods.
125 studies on the registry are indexed under Antiphospholipid Syndrome; 55 are open to participants now.
This study's planned enrollment of 234 is above the median of 40 across 67 interventional studies indexed under Antiphospholipid Syndrome.
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Exclusion Criteria:
Participants in this arm discontinue vitamin K antagonist (VKA) therapy at the randomisation visit. Anticoagulant treatment duration in this arm is 0 month. International Normalized Ratio (INR) testing is performed at baseline (M0) and then discontinued. Participants are followed according to the study visit schedule (M3, M6, then every 6 months up to M48), with clinical and biological assessments including antiphospholipid antibody (aPL) measurement, and are restarted on anticoagulant therapy only in case of a recurrent thrombotic event.
Other: Anticoagulant Therapy Discontinuation
Participants in this arm continue vitamin K antagonist (VKA) therapy (fluindione, warfarin, or acenocoumarol), dosed orally to obtain an International Normalized Ratio (INR) between 2 and 3, for a minimum of 24 months (up to 48 months depending on time of enrollment). INR is monitored at baseline (M0), at M3, at each subsequent protocol visit, in case of recurrent thrombotic event, and as clinically indicated. Participants are also followed with clinical and biological assessments including antiphospholipid antibody (aPL) measurement. Participants follow the same visit schedule as the experimental arm (M3, M6, then every 6 months up to M48)
Drug: Vitamin K Antagonist - Drug
Continuation of vitamin K antagonist therapy (fluindione, warfarin, or acenocoumarol), administered orally and dosed to obtain an International Normalized Ratio (INR) between 2 and 3, for a minimum of 24 months (up to 48 months depending on time of enrollment)
Also known as: Fluindione, Warfarine, Acénocoumarol
Discontinuation of vitamin K antagonist therapy at the randomisation visit. No anticoagulant treatment is administered during follow-up unless a recurrent thrombotic event occurs
First Recurrent Of Thrombotic Event
Occurrence of a first recurrent thrombotic event during follow-up, in patients randomised to anticoagulation cessation compared to anticoagulation maintenance.
Time frame: Up to 48 months
Health-Related Quality of Life
Change in health-related quality of life assessed using the 36-Item Short Form Health Survey (SF-36), a patient-reported outcome questionnaire comprising 8 subscales, each scored from 0 to 100. Higher scores indicate better health-related quality of life.
Time frame: At baseline and at each follow-up visit, up to 48 months
Major Bleeding Events
Number of major bleeding events during follow-up, with and without anticoagulant therapy. Major bleeding is defined as: a) fatal bleeding; and/or b) bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome; and/or c) bleeding causing a fall in hemoglobin level of 2 g/dL or more, or leading to transfusion
Time frame: Up to 48 months
All-Cause Mortality
All-causes mortality rate during follow-up, compared between the anticoagulation cessation and anticoagulation maintenance arms.
Time frame: Up to 48 months
Risk Factors Associated With Recurrent Thrombosis
Baseline and clinical characteristics (age, gender, obesity, surgeries, trauma, immobilization, infection, malignancy, pregnancy, contraceptive agents, primary/secondary APS status, aPL profile, aPL reappearance) analyzed in relation to the occurrence of recurrent thrombosis after anticoagulation cessation.
Time frame: Up to 48 months
Incidence of aPL Reappearance
Incidence of aPL reappearance during follow-up, in patients with and without anticoagulant therapy after aPL loss. Reappearance is defined as a normalised level (\>99th percentile) of LA, aCL, or aβ2GPI antibodies in at least one measurement during follow-up.
Time frame: Up to 48 months
Plan to share: Undecided
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Start is estimated for Dec 2026; primary completion for Dec 2030, 48 months later.
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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