Antiphospholipid SyndromePhase 3ADORANCT07875153
Anticoagulant Cessation After Antiphospholipid Autoantibodies Loss in Thrombotic Antiphospholipid Syndrome
A Phase 3 study testing Vitamin K Antagonist - Drug and Anticoagulant Therapy Discontinuation in people with Antiphospholipid Syndrome and Thrombotic Antiphospholipid Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antiphospholipid Syndrome, Thrombotic Antiphospholipid Syndrome, Thrombosis
- What is being tested?
- Vitamin K Antagonist - Drug and Anticoagulant Therapy Discontinuation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 234 participants
- Where
- 1 siteFrance
- Study dates
- Dec 2026to Jan 2031
- Phase
- Phase 3
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
Who may be able to join
- Adults ≥ 18 years old
- Signed written consent form
- Primary or secondary thrombotic APS according to 2023 ACR/EULAR classification criteria
- aPL antibodies loss of LA, aCL, and aβ2GPI antibodies - defined as a normalised level (< 99th percentile) - in at least two consecutive measurements with at least 12 months between each measurement including one negative measurement within the 3 months preceding inclusion
- Long term (>12 months) VKAs therapy
Who cannot join
- History of severe venous thrombosis. Severe venous thrombosis including massive pulmonary embolism; chronic thromboembolic pulmonary hypertension; hepatic, mesenteric, renal and/or cerebral venous thrombosis
- History of arterial thrombosis
- History of recurrent venous thrombosis while receiving VKAs
- History of catastrophic antiphospholipid syndrome (CAPS)
- Triple aPL positivity
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 for each VKAs medicinal product
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- Malignant hypertension
- Severe hepatic impairment
- Active malignancy
- Presence of a mechanical heart valve or any other medical condition requiring anticoagulation with a VKA
- Pregnancy or breastfeeding
- Subject deprived of freedom, subject under a legal protective measure
- No affiliation to any health insurance system
- Enrolment to another interventional study (clinical trial on medicinal product, medical device and interventional research involving human participants not concerning health product)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
AP-HP Hôpital Bichat - Claude Bernard
Paris, 75018
KARIM SACRE, MD, 01.40.25.60.19, karim.sacre@aphp.fr
ARTHUR MAGEAU, MD, 01.40.25.87.06, arthur.mageau@aphp.fr
About this study
Official title: A Randomised Controlled Trial to Evaluate Anticoagulant Cessation After Antiphospholipid Autoantibodies Loss in Thrombotic Antiphospholipid Syndrome
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.
Read the detailed description
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.
- Being tested
- Vitamin K Antagonist - Drug, Anticoagulant Therapy Discontinuation
- Keywords
- antiphospholipid antibodies, vitamin K antagonists, PROBE design, non-inferiority trial, recurrent thrombosis
- Medical subject headings
- Antiphospholipid Syndrome, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin K Antagonist - DrugDrug
Also called Fluindione, Warfarine, Acénocoumarol
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)
Anticoagulant Therapy DiscontinuationOther
Discontinuation of vitamin K antagonist therapy at the randomisation visit. No anticoagulant treatment is administered during follow-up unless a recurrent thrombotic event occurs
| Study group | Role | What they receive |
|---|---|---|
| Anticoagulation Cessation | Experimental | 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. Receives: Other: Anticoagulant Therapy Discontinuation |
| Anticoagulation Maintenance | Active comparator | 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) Receives: Drug: Vitamin K Antagonist - Drug |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 48 months
Secondary outcomes (5)
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.
Measured: 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
Measured: Up to 48 months
All-Cause Mortality
All-causes mortality rate during follow-up, compared between the anticoagulation cessation and anticoagulation maintenance arms.
Measured: 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.
Measured: 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.
Measured: Up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2026
- Study startDec 2026 (estimated)
- Primary completionDec 2030 (estimated)
- Study completionJan 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Antiphospholipid SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The trial follows a PROBE (Prospective Randomized Open, Blinded Endpoint) design: treatment allocation is open-label (neither patients nor investigators are blinded to the assigned arm), but the assessment of the primary endpoint follows blinded evaluation procedures to limit detection bias
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 234 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Direction Générale de l'Offre de Soin (DGOS)
- Responsible party
- Sponsor
- Investigators
- KARIM SACRE, MD, Study chair, Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Bichat, Department of Internal Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07875153
- Sponsor's protocol ID
- APHP251593
- Other IDs
- 2026-526448-12-00
- Acronym
- ADORA
- Status last verified
- Sep 2026
- First submitted
- 10 Sep 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided