Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04275778
Other study ID # P160944J
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date July 9, 2021
Est. completion date October 2, 2025

Study information

Verified date February 2022
Source Assistance Publique - Hôpitaux de Paris
Contact Olivier FAIN, MD-PhD
Phone 01 49 28 21 04
Email olivier.fain@aphp.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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.


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..


Recruitment information / eligibility

Status Recruiting
Enrollment 110
Est. completion date October 2, 2025
Est. primary completion date October 2, 2024
Accepts healthy volunteers No
Gender Female
Age group 18 Years to 48 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
France Hopital Saint Antoine Paris

Sponsors (1)

Lead Sponsor Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (5)

Fain O, Mekinian A. [Antiphospholipid syndrome]. Rev Prat. 2011 Nov;61(9):1261-2. French. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of term pregnancies with a eutrophic child eutrophic child = a full term birth without maternal, fetal or neonatal complications at delivery
See also
  Status Clinical Trial Phase
Terminated NCT02128841 - Comparison of Antithrombotic Treatments After Aortic Valve Replacement. Rivaroxaban: A New Antithrombotic Treatment for Patients With Mechanical Prosthetic Aortic Heart Valve. Phase 2
Recruiting NCT03666962 - Evaluating Medication Adherence to Novel Oral Anticoagulants With Anticoagulant Activity Monitoring in Patients With Atrial Fibrillation
Recruiting NCT03670446 - Pharmacists' Intervention in Patients Using Novel Oral Anticoagulants:A Study on Behavioral Patterns N/A
Recruiting NCT04796714 - AntiPlatelet theraPy stratEgy followiNg Left Atrial appenDAGe closurE Phase 4
Completed NCT01033279 - Quality of Life and Efficacy Evaluation of Patient Self-monitoring Their Oral Anticoagulation Therapy N/A
Completed NCT00287313 - Daily Vitamin K in Patients on Warfarin With Unstable INRs N/A
Completed NCT00222638 - Influenza Vaccination and Oral Anticoagulant Therapy Phase 4
Active, not recruiting NCT06203795 - Dialysis Performance of the FX CorAL Membrane N/A
Completed NCT03864900 - Efficacy of a Health Belief Model Based Intervention for Anticoagulation Adherence N/A
Active, not recruiting NCT06401863 - Shared Decision for Drug Interactions in Oral Anticoagulation N/A
Not yet recruiting NCT04977076 - Comparison Between Direct Oral Anticoagulation (DOAC) Interruption and DOAC Continuation in Patients Undergoing Elective Invasive Coronary Angiography or Percutaneous Coronary Intervention N/A
Recruiting NCT04861103 - Anticoagulation Profile in Pregnant Women Treated With Three Times a Day of Low Molecular Weight Heparin (LMWH) Phase 4
Completed NCT01653405 - Improving Anticoagulation Control in VISN 1 N/A
Not yet recruiting NCT05820854 - Self-care and Self-efficacy Scale in Oral Anticoagulation Therapy
Completed NCT04681482 - Effectiveness And Safety Of Oral Anticoagulants Among Obese Patients With Non-Valvular A-Fib In VA Patients With Medicare
Not yet recruiting NCT06137794 - Application of "I-Anticoagulation"in Patients With Atrial Fibrillation N/A
Completed NCT02103101 - Influence of ABCB1 Polymorphisms on Plasma Concentrations of New Oral Anticoagulants in Case of Serious Adverse Events N/A
Completed NCT05065502 - MIDAS Cluster Randomized Controlled Trial of Implementation Strategies to Optimize Use of Medications in VA Clinical Settings N/A
Recruiting NCT03965208 - Safety and Efficacy of Bivalirudin Versus Heparin for Systemic Anticoagulation in Extracorporeal Membrane Oxygenation Phase 4
Completed NCT03318393 - Study Comparing Bivalirudin Versus Heparin in Neonatal and Pediatric ECMO Phase 4