HYDROxychloroquine in Syndrome Primary AntiPhospholipid

NCT04275778 | Unknown Phase 2

• 1 other identifier: P160944J
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Antiphospholipid Syndrome in Pregnancy; Anticoagulants

Keywords

APS; Anticoagulants; Pregancy; Heparin Low-Molecular-Weight; Aspirin

Outcome Measures

Primary Outcomes (1)

• Percentage of term pregnancies with a eutrophic child

  eutrophic child = a full term birth without maternal, fetal or neonatal complications

  at delivery

Study Arms (2)

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.

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.

Drug: Placebo oral tablet

Interventions

Plaquenil 200Mg Tablet DRUG

Hydroxychloroquine will be taken at a dosage of 400 mg / day until delivery

Hydroxychloroquine

Placebo oral tablet DRUG

placebo will be taken at a dosage of 400 mg / day until delivery

Placebo group

Eligibility Criteria

• Age: 18 Years - 48 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• Patient under guardianship or curatorship
• Patient deprived of liberty
• Lack of Social Insurance

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hopital Saint Antoine

Paris, 75012, France

RECRUITING

Related Publications (5)

• 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.

  PMID: 20822807 BACKGROUND

• Fain O, Mekinian A. [Antiphospholipid syndrome]. Rev Prat. 2011 Nov;61(9):1261-2. No abstract available. French.

  PMID: 22308813 BACKGROUND

• Mekinian 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.

  PMID: 22589374 BACKGROUND

• Mekinian 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.

  PMID: 22386067 BACKGROUND

• Mekinian 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.

  PMID: 25617818 BACKGROUND

MeSH Terms

Interventions

Hydroxychloroquine

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Arsène MEKINIAN, MD

  Internal Medecine_Hospital Saint Antoine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olivier FAIN, MD-PhD

CONTACT

01 49 28 21 04; olivier.fain@aphp.fr

Arsène MEKINIAN, MD

CONTACT

01 49 28 21 04; arsene.mekinian@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Hydroxychloroquine and placebo will be provided by "AGEPS" which outsources these drugs fabrication. The "AGEPS" outsources operations which are technically non-feasible locally, or if the volume or logistical constraints are inconsistent with the balance of its human and material resources.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 17, 2020
• First Posted: February 19, 2020
• Study Start: July 9, 2021
• Primary Completion: October 2, 2024
• Study Completion: October 2, 2025
• Last Updated: March 2, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)