HYDROxychloroquine in Syndrome Primary AntiPhospholipid

• Status: Not yet recruiting
• Trial end date: 2025-10-02
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Hydroxychloroquine

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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