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
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 110
- 试验地点
- 2
- 主要终点
- Percentage of term pregnancies with a eutrophic child
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 48 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Hydroxychloroquine
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.
干预措施: Plaquenil 200Mg Tablet (Drug)
Placebo group
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.
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Percentage of term pregnancies with a eutrophic child
时间窗: at delivery
eutrophic child = a full term birth without maternal, fetal or neonatal complications
次要结局
未报告次要终点