Antiphospholipid Syndrome in PregnancyPhase 2HYDROSAPLNCT04275778
HYDROxychloroquine in Syndrome Primary AntiPhospholipid
A Phase 2 study testing Plaquenil 200Mg Tablet in people with Antiphospholipid Syndrome in Pregnancy and Anticoagulants, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Antiphospholipid syndrome (APS) is defined by thrombosis or obstetric complication (≥ 3 spontaneous miscarriages or fetal death or prematurity <34 weeks gestation-related amenorrhea (SA)) associated with antiphospholipid antibodies. Read more about this study
- Who is it for?
- Ages 18 to 48 years, women only
- Conditions the study is for
- Antiphospholipid Syndrome in Pregnancy, Anticoagulants
- What is being tested?
- Plaquenil 200Mg Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- 9 Jul 2021to 2 Oct 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 48 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Age >18 years
- Spontaneous consecutive pregnancy ongoing before the 14th week of gestation
- -- SAPL obstetrics (modified Sapporo criteria = Sydney criteria) with fetal death ≥10 weeks of gestation without further explanation; and / or preeclampsia (or HELLP syndrome) and / or prematurity <34SA with placental insufficiency (with or without thrombotic SAPL)
- Signed informed consent
Who cannot join
- Other SAPL subgroups: early isolated miscarriages <10 weeks
- Contraindication to hydroxychloroquine:
- retinopathy,
- hypersensitivity to chloroquine or hydroxychloroquine or to any of the other ingredients especially lactose
- Associated systemic lupus, associated Sjogren syndrome
- Treatment with hydroxychloroquine in progress
Show all 9Show fewer
- Patient under guardianship or curatorship
- Patient deprived of liberty
- Lack of Social Insurance
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of the Benefit of Adjuvant Treatment With Hydroxychloroquine to the Usual Medical Management for Obtaining an Uncomplicated Term Pregnancy in Primary Obstetric Antiphospholipid Syndrome
Antiphospholipid syndrome (APS) is defined by thrombosis or obstetric complication (≥ 3 spontaneous miscarriages or fetal death or prematurity <34 weeks gestation-related amenorrhea (SA)) associated with antiphospholipid antibodies. The rate of term pregnancies has been improved by conventional treatment (aspirin 100 mg / day with low molecular weight heparin (LMWH) in an isocoagulant dose) to almost 75%. In the PROMISSE study, when considering progressive pregnancies after 20 weeks, 19% of pregnancies presented at least one complication despite the treatment (maternal, fetal or neonatal complications) related to APS. In the European APS register, maternal complications and IUGR were observed in 13% of cases, and prematurity in approximately 14% of cases despite treatment. In a previous study of 72 pregnancies during a LAS, we observed, under aspirin and LMWH, 25% of fetal losses, and 10% of at least one maternal and / or fetal complication or prematurity. The presence of lupus, a history of thrombosis, a circulating anticoagulant (ACC) and a triple positivity of antiphospholipids are considered to be factors associated with a poor obstetrical prognosis. Hydroxychloroquine (HCQ) has anti-inflammatory and anti-thrombotic properties. In vitro studies have shown that HCQ is able to restore the expression of placental annexin V, which has an anticoagulant effect and prevent the attachment of antiphospholipid antibodies to the placenta.
HCQ during lupus decreases the thrombotic risk and its usefulness during thrombotic APS has been shown in a French series. In a European study, the addition of the HCQ to conventional treatment improved term pregnancies by 70% in the event of refractory APS. Its use during pregnancies of patients with lupus, the numerous data on tolerance during pregnancy and the follow-up of children born to mothers exposed to the HCQ demonstrates a reassuring tolerance profile for the mother and the fetus.
The objective of this clinical trial is to evaluate the benefit of addition or no of hydroxychloroquine to conventional treatment in obstetric APS.
Read the detailed description
The consecutive patientes with APS will be recruited in different ways based on daily practice; Patients fulfilling all criteria may be randomized following receipt of written informed consent.
The randomization will be stratified by center and by, the presence of anticoagulant antibody.
Te included patients will be randomized to receive conventional APS treatment (aspirin with low-molecular-weight heparin) combined with hydroxychloroquine or placebo.
In the two groups, the hydroxychloroquine or placebo will be initiated in the patients with ongoing pregnancy (≤14 week of gestation).
After the inclusion visit, the patients will be followed by the investigator every months until the end of the pregnancy and at 6 weeks postpartum.
At each visit, a clinical examination, routine biological analysis, APL antibody and complement determination will be performed. Hydroxychloroquine blood levels, PFA, Xa inhibition,and treatment adherence will be assessed during pregnancy.
At Inclusion :
- Maternal blood samples 20 ml of blood will be collected at the same time as the sample routinely collected just before delivery when the women are perfused.
At delivery
- Cord fluid : will be collected at the same as cord fluid pH is routinely measured just after delivery. The aliquots previously labelled and stowed in the specific boxes for the study will be stored locally and will be transported to the "Centre de Ressources Biologiques"(CRB) of the Saint Antoine Hospital. Last visit for children : At 12 months The patient will be contacted by phone by the local medical team to collect the following data: Children's anthropometric data; safety data ; possible hospitalization..
- Being tested
- Plaquenil 200Mg Tablet, Placebo oral tablet
- Keywords
- APS, Anticoagulants, Pregancy, Heparin Low-Molecular-Weight, Aspirin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plaquenil 200Mg TabletDrug
Hydroxychloroquine will be taken at a dosage of 400 mg / day until delivery
Placebo oral tabletDrug
placebo will be taken at a dosage of 400 mg / day until delivery
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine | Active comparator | Hydroxychloroquine will be prescribed upon confirmation of pregancy at a dosage of 400 mg / day. Either in 2 doses (1 tablet of 200 mg in the morning and 1 tablet of 200 mg in the evening). Or in a single take: 2 tablets of 200 mg.
Treatment will be continueted during the pregnancy and will be stopped at delivery. Receives: Drug: Plaquenil 200Mg Tablet |
| Placebo group | Placebo comparator | Placebo will be prescribed upon confirmation of pregancy at a dosage of 400 mg / day. Either in 2 doses (1 tablet of 200 mg in the morning and 1 tablet of 200 mg in the evening). Or in a single take: 2 tablets of 200 mg.
Treatment will be continueted during the pregnancy and will be stopped at delivery. Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of term pregnancies with a eutrophic child
eutrophic child = a full term birth without maternal, fetal or neonatal complications
Measured: at delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start9 Jul 2021
- Primary completion2 Oct 2024 (estimated)
- Study completion2 Oct 2025 (estimated)
Why it stopped: The study was terminated following revisions to the diagnostic criteria defining the target pathology, which significantly impacted the study design
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 in PregnancyStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Group 1 : Hydroxychloroquine Group 2 : Placebo d'hydroxychloroquine Hydroxychloroquine or placebo will be performed at 2 pills (400 mg) per day, during the pregnancy, and stopped at delivery. The conventional treatment will be the same in the 2 groups: * aspirin 100 mg/day will begin , the preference at the preconception, and continued during pregnancy and will be stopped at 35 weeks of gestation. LMWH enoxaparin 4000 UI/day will begin as soon as possible after confirmation of the pregnancy, and will be continued during 6 weeks postpartum.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Arsène MEKINIAN, MD, Principal investigator, Internal Medecine_Hospital Saint Antoine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04275778
- Sponsor's protocol ID
- P160944J
- Acronym
- HYDROSAPL
- Status last verified
- Feb 2026
- First submitted
- 17 Feb 2020
- Last updated
- 6 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet. 2010 Oct 30;376(9751):1498-509. doi: 10.1016/S0140-6736(10)60709-X. Epub 2010 Sep 6.
PubMed 20822807Fain O, Mekinian A. [Antiphospholipid syndrome]. Rev Prat. 2011 Nov;61(9):1261-2. No abstract available. French.
PubMed 22308813Mekinian A, Lachassinne E, Nicaise-Roland P, Carbillon L, Motta M, Vicaut E, Boinot C, Avcin T, Letoumelin P, De Carolis S, Rovere-Querini P, Lambert M, Derenne S, Pourrat O, Stirnemann J, Chollet-Martin S, Biasini-Rebaioli C, Rovelli R, Lojacono A, Ambrozic A, Botta A, Benbara A, Pierre F, Allegri F, Nuzzo M, Hatron PY, Tincani A, Fain O, Aurousseau MH, Boffa MC. European registry of babies born to mothers with antiphospholipid syndrome. Ann Rheum Dis. 2013 Feb;72(2):217-22. doi: 10.1136/annrheumdis-2011-201167. Epub 2012 May 15.
PubMed 22589374Mekinian A, Loire-Berson P, Nicaise-Roland P, Lachassinne E, Stirnemann J, Boffa MC, Chollet-Martin S, Carbillon L, Fain O. Outcomes and treatment of obstetrical antiphospholipid syndrome in women with low antiphospholipid antibody levels. J Reprod Immunol. 2012 Jun;94(2):222-6. doi: 10.1016/j.jri.2012.02.004. Epub 2012 Mar 3.
PubMed 22386067Mekinian A, Lazzaroni MG, Kuzenko A, Alijotas-Reig J, Ruffatti A, Levy P, Canti V, Bremme K, Bezanahary H, Bertero T, Dhote R, Maurier F, Andreoli L, Benbara A, Tigazin A, Carbillon L, Nicaise-Roland P, Tincani A, Fain O; SNFMI and the European Forum on Antiphospholipid Antibodies. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study. Autoimmun Rev. 2015 Jun;14(6):498-502. doi: 10.1016/j.autrev.2015.01.012. Epub 2015 Jan 21.
PubMed 25617818
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Benefit of Adjuvant Treatment With Hydroxychloroquine to the Usual Medical Management for Obtaining an Uncomplicated Term Pregnancy in Primary Obstetric Antiphospholipid Syndrome
- ClinicalTrials.gov ID
- NCT04275778
- Acronym / sponsor ID
- HYDROSAPL / P160944J
- Keywords
- APS, Anticoagulants, Pregancy, Heparin Low-Molecular-Weight, Aspirin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was terminated following revisions to the diagnostic criteria defining the target pathology, which significantly impacted the study design
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 9 Jul 2021 (actual)
- Primary completion
- 2 Oct 2024 (estimated)
- Study completion
- 2 Oct 2025 (estimated)
- First posted
- 19 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Antiphospholipid syndrome (APS) is defined by thrombosis or obstetric complication (≥ 3 spontaneous miscarriages or fetal death or prematurity <34 weeks gestation-related amenorrhea (SA)) associated with antiphospholipid antibodies. The rate of term pregnancies has been improved by conventional treatment (aspirin 100 mg / day with low molecular weight heparin (LMWH) in an isocoagulant dose) to almost 75%. In the PROMISSE study, when considering progressive pregnancies after 20 weeks, 19% of pregnancies presented at least one complication despite the treatment (maternal, fetal or neonatal complications) related to APS. In the European APS register, maternal complications and IUGR were observed in 13% of cases, and prematurity in approximately 14% of cases despite treatment. In a previous study of 72 pregnancies during a LAS, we observed, under aspirin and LMWH, 25% of fetal losses, and 10% of at least one maternal and / or fetal complication or prematurity. The presence of lupus, a history of thrombosis, a circulating anticoagulant (ACC) and a triple positivity of antiphospholipids are considered to be factors associated with a poor obstetrical prognosis. Hydroxychloroquine (HCQ) has anti-inflammatory and anti-thrombotic properties. In vitro studies have shown that HCQ is able to restore the expression of placental annexin V, which has an anticoagulant effect and prevent the attachment of antiphospholipid antibodies to the placenta.
HCQ during lupus decreases the thrombotic risk and its usefulness during thrombotic APS has been shown in a French series. In a European study, the addition of the HCQ to conventional treatment improved term pregnancies by 70% in the event of refractory APS. Its use during pregnancies of patients with lupus, the numerous data on tolerance during pregnancy and the follow-up of children born to mothers exposed to the HCQ demonstrates a reassuring tolerance profile for the mother and the fetus.
The objective of this clinical trial is to evaluate the benefit of addition or no of hydroxychloroquine to conventional treatment in obstetric APS.
Detailed description
The consecutive patientes with APS will be recruited in different ways based on daily practice; Patients fulfilling all criteria may be randomized following receipt of written informed consent.
The randomization will be stratified by center and by, the presence of anticoagulant antibody.
Te included patients will be randomized to receive conventional APS treatment (aspirin with low-molecular-weight heparin) combined with hydroxychloroquine or placebo.
In the two groups, the hydroxychloroquine or placebo will be initiated in the patients with ongoing pregnancy (≤14 week of gestation).
After the inclusion visit, the patients will be followed by the investigator every months until the end of the pregnancy and at 6 weeks postpartum.
At each visit, a clinical examination, routine biological analysis, APL antibody and complement determination will be performed. Hydroxychloroquine blood levels, PFA, Xa inhibition,and treatment adherence will be assessed during pregnancy.
At Inclusion :
- Maternal blood samples 20 ml of blood will be collected at the same time as the sample routinely collected just before delivery when the women are perfused.
At delivery
- Cord fluid : will be collected at the same as cord fluid pH is routinely measured just after delivery. The aliquots previously labelled and stowed in the specific boxes for the study will be stored locally and will be transported to the "Centre de Ressources Biologiques"(CRB) of the Saint Antoine Hospital. Last visit for children : At 12 months The patient will be contacted by phone by the local medical team to collect the following data: Children's anthropometric data; safety data ; possible hospitalization..
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Group 1 : Hydroxychloroquine Group 2 : Placebo d'hydroxychloroquine Hydroxychloroquine or placebo will be performed at 2 pills (400 mg) per day, during the pregnancy, and stopped at delivery. The conventional treatment will be the same in the 2 groups: * aspirin 100 mg/day will begin , the preference at the preconception, and continued during pregnancy and will be stopped at 35 weeks of gestation. LMWH enoxaparin 4000 UI/day will begin as soon as possible after confirmation of the pregnancy, and will be continued during 6 weeks postpartum.
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine | Active comparator | Drug: Plaquenil 200Mg TabletHydroxychloroquine will be prescribed upon confirmation of pregancy at a dosage of 400 mg / day. Either in 2 doses (1 tablet of 200 mg in the morning and 1 tablet of 200 mg in the evening). Or in a single take: 2 tablets of 200 mg. Treatment will be continueted during the pregnancy and will be stopped at delivery. |
| Placebo group | Placebo comparator | Drug: Placebo oral tabletPlacebo will be prescribed upon confirmation of pregancy at a dosage of 400 mg / day. Either in 2 doses (1 tablet of 200 mg in the morning and 1 tablet of 200 mg in the evening). Or in a single take: 2 tablets of 200 mg. Treatment will be continueted during the pregnancy and will be stopped at delivery. |
Who may qualify
- Ages
- 18 to 48 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age >18 years
- Spontaneous consecutive pregnancy ongoing before the 14th week of gestation
- -- SAPL obstetrics (modified Sapporo criteria = Sydney criteria) with fetal death ≥10 weeks of gestation without further explanation; and / or preeclampsia (or HELLP syndrome) and / or prematurity <34SA with placental insufficiency (with or without thrombotic SAPL)
- Signed informed consent
Key exclusion criteria (9 listed)
- Other SAPL subgroups: early isolated miscarriages <10 weeks
- Contraindication to hydroxychloroquine:
- Associated systemic lupus, associated Sjogren syndrome
- Treatment with hydroxychloroquine in progress
- Patient under guardianship or curatorship
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plaquenil 200Mg TabletHydroxychloroquine will be taken at a dosage of 400 mg / day until delivery | Drug | Hydroxychloroquine |
| Placebo oral tabletplacebo will be taken at a dosage of 400 mg / day until delivery | Drug | Placebo group |
Primary outcome
Percentage of term pregnancies with a eutrophic child
Time frame: at delivery
eutrophic child = a full term birth without maternal, fetal or neonatal complications
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2026.
- Background: PubMed 20822807Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet. 2010 Oct 30;376(9751):1498-509. doi: 10.1016/S0140-6736(10)60709-X. Epub 2010 Sep 6.
- Background: PubMed 22308813Fain O, Mekinian A. [Antiphospholipid syndrome]. Rev Prat. 2011 Nov;61(9):1261-2. No abstract available. French.
- Background: PubMed 22589374Mekinian A, Lachassinne E, Nicaise-Roland P, Carbillon L, Motta M, Vicaut E, Boinot C, Avcin T, Letoumelin P, De Carolis S, Rovere-Querini P, Lambert M, Derenne S, Pourrat O, Stirnemann J, Chollet-Martin S, Biasini-Rebaioli C, Rovelli R, Lojacono A, Ambrozic A, Botta A, Benbara A, Pierre F, Allegri F, Nuzzo M, Hatron PY, Tincani A, Fain O, Aurousseau MH, Boffa MC. European registry of babies born to mothers with antiphospholipid syndrome. Ann Rheum Dis. 2013 Feb;72(2):217-22. doi: 10.1136/annrheumdis-2011-201167. Epub 2012 May 15.
- Background: PubMed 22386067Mekinian A, Loire-Berson P, Nicaise-Roland P, Lachassinne E, Stirnemann J, Boffa MC, Chollet-Martin S, Carbillon L, Fain O. Outcomes and treatment of obstetrical antiphospholipid syndrome in women with low antiphospholipid antibody levels. J Reprod Immunol. 2012 Jun;94(2):222-6. doi: 10.1016/j.jri.2012.02.004. Epub 2012 Mar 3.
- Background: PubMed 25617818Mekinian A, Lazzaroni MG, Kuzenko A, Alijotas-Reig J, Ruffatti A, Levy P, Canti V, Bremme K, Bezanahary H, Bertero T, Dhote R, Maurier F, Andreoli L, Benbara A, Tigazin A, Carbillon L, Nicaise-Roland P, Tincani A, Fain O; SNFMI and the European Forum on Antiphospholipid Antibodies. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study. Autoimmun Rev. 2015 Jun;14(6):498-502. doi: 10.1016/j.autrev.2015.01.012. Epub 2015 Jan 21.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arsène MEKINIAN, MD principal investigator
Internal Medecine_Hospital Saint Antoine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Plaquenil 200Mg Tablet in people with Antiphospholipid Syndrome in Pregnancy and Anticoagulants, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of term pregnancies with a eutrophic child (time frame: at delivery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04275778, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2026; AzTrials last refreshed its copy on 30 Oct 2026.