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Trial record 1 of 9 for:    Recruiting Studies | Antiphospholipid Syndrome | France
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HYDROxychloroquine in Syndrome Primary AntiPhospholipid (HYDROSAPL)

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ClinicalTrials.gov Identifier: NCT04275778
Recruitment Status : Recruiting
First Posted : February 19, 2020
Last Update Posted : March 2, 2022
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.


Condition or disease Intervention/treatment Phase
Antiphospholipid Syndrome in Pregnancy Anticoagulants Drug: Plaquenil 200Mg Tablet Drug: Placebo oral tablet Phase 2

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..

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Investigator)
Masking Description: 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.
Primary Purpose: Treatment
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
Actual Study Start Date : July 9, 2021
Estimated Primary Completion Date : October 2, 2024
Estimated Study Completion Date : October 2, 2025


Arm Intervention/treatment
Active Comparator: 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.

Drug: Plaquenil 200Mg Tablet
Hydroxychloroquine will be taken at a dosage of 400 mg / day until delivery

Placebo Comparator: 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.

Drug: Placebo oral tablet
placebo will be taken at a dosage of 400 mg / day until delivery




Primary Outcome Measures :
  1. Percentage of term pregnancies with a eutrophic child [ Time Frame: at delivery ]
    eutrophic child = a full term birth without maternal, fetal or neonatal complications



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 48 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04275778


Contacts
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Contact: Olivier FAIN, MD-PhD 01 49 28 21 04 ext 00 33 olivier.fain@aphp.fr
Contact: Arsène MEKINIAN, MD 01 49 28 21 04 ext 00 33 arsene.mekinian@aphp.fr

Locations
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France
Hopital Saint Antoine Recruiting
Paris, France, 75012
Contact: Makinian Pr Arsène    +33149282104    arsene.mekinian@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Arsène MEKINIAN, MD Internal Medecine_Hospital Saint Antoine
Publications:

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04275778    
Other Study ID Numbers: P160944J
First Posted: February 19, 2020    Key Record Dates
Last Update Posted: March 2, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
APS
Anticoagulants
Pregancy
Heparin Low-Molecular-Weight
Aspirin
Additional relevant MeSH terms:
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Antiphospholipid Syndrome
Syndrome
Disease
Pathologic Processes
Autoimmune Diseases
Immune System Diseases
Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents