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Hydroxychloroquine for prevention of recurrent miscarriage: study protocol for a multicentre randomised placebo-controlled trial BBQ study
  1. Elisabeth Pasquier1,
  2. Luc de Saint-Martin2,
  3. Gisèle Marhic3,
  4. Celine Chauleur4,
  5. Caroline Bohec5,
  6. Florence Bretelle6,
  7. Véronique Lejeune-Saada7,
  8. Jacob Hannigsberg8,
  9. Geneviève Plu-Bureau9,
  10. Virginie Cogulet10,
  11. Philippe Merviel8,
  12. Dominique Mottier11
  1. 1EA 3878, Brest University Hospital, Brest, France
  2. 2EA 3878 Groupe d’Etude de la Thrombose de Bretagne Occidentale, Brest, France
  3. 3Centre d’Investigation Clinique-INSERM 1412, Brest, France
  4. 4Thrombosis Research Group, University Hospital Bellevue, Saint-Etienne, France
  5. 5Division of Gynaecology, Hôpital François Mitterand, Pau, France
  6. 6Division of Gynaecology, Université de la Méditerranée, Hôpital Nord, Marseille, France
  7. 7Division of Gynaecology, Hôpital d’Auch, Auch, France
  8. 8Division of Gynecology, Brest University Hospital, Brest, France
  9. 9Division of Gynaecology, APHP, Hôpital Cochin, Paris, France
  10. 10Department of Pharmacy, Brest University Hospital, Brest, France
  11. 11Brest University Hospital, Brest, France
  1. Correspondence to Dr Elisabeth Pasquier; elisabeth.pasquier{at}chu-brest.fr

Abstract

Introduction Recurrent miscarriage (RM), defined by three or more consecutive losses during the first trimester of pregnancy, affects 1%–2% of fertile couples. Standard investigations fail to reveal any apparent cause in ~50% of couples. However, on the basis of animal models and clinical studies, several hypotheses have been put forward concerning underlying mechanisms of RM: altered ovarian reserve, progesterone defect, thrombotic and/or endothelial dysfunction and immunological disturbances. Nonetheless, no study has yet reached conclusive beneficial clinical evidence for a potential treatment in unexplained RM. Hydroxychloroquine (HCQ) is a molecule with extensive safety data during pregnancy. The pharmacological properties of HCQ (eg, antithrombotic, vascular protective, immunomodulatory, improved glucose tolerance, lipidlowering and anti-infectious) could be effective against some mechanisms of unexplained RM. Furthermore, eventhough clinical benefit of HCQ is suggested in prevention of thrombotic and late obstetric events in antiphospholipid (APL) syndrome, there are no data suggesting the benefit of HCQ in RM in the presence of APL antibodies.

Methods and analysis Taken all together and given the low cost of HCQ, the aim of this multicentre, randomised, placebo-controlled, double-blind study is to investigate whether HCQ would improve the live birth rate in women with RM, irrespective of maternal thrombophilic status: (1) no known thrombophilia, (2) inherited thrombophilia or (3) APL antibodies. The primary end point is a live and viable birth. After confirming eligibility and obtaining consent, 300 non-pregnant women will be randomised into two parallel groups for a daily oral treatment (HCQ 400 mg or placebo), initiated before conception and stopped at 10 weeks’ gestation. If pregnancy does not occur after 1 year, the treatment will be stopped.

Ethics and dissemination Agreement from the French National Public Health and Drug Security Agency (160765A-22) and ethical approval from the Committee for the Protection of Persons of NORD-OUEST I (2016-001330-97) have been obtained.

Trial registration numbers NCT0316513; Pre-results.

  • subfertility
  • internal medicine
  • clinical trials

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Footnotes

  • Contributors EP conceived and designed the study. EP drafted the original grant proposal and trial protocol. LDS-M provides methodological and statistical expertise. GM has assisted in developing the protocol, helped with implementation and has responsibilities for day-to-day running of the trial including participant recruitment, data collection and liaising with other sites. JH and PM have helped with protocol implementation. CB, CC, FB, VL-S, GP-B and DM have participated in the design of the study. VC coordinates treatment production and dispensation. All authors critically reviewed and approved the final version of the manuscript.

  • Funding The study was supported by a grant from the French Ministry of Health (PHRCN-17-0573).

  • Competing interests None declared.

  • Ethics approval Agreement from the French National Public Health and Drug Security Agency (160765A-22) and ethical approval from the Committee for the Protection of Persons of NORD-OUEST I (2016-001330-97) have been obtained on 4 November 2016 and 2 March 2017, respectively.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent for publication Obtained.

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