Hydroxychloroquine for Prevention of Recurrent Miscarriage.

NCT03165136 | Unknown Phase 3 DMC

• 1 other identifier: 29BRC16.0045
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 18

Brief Summary

Recurrent miscarriage (RM) defined by \>=3 consecutive losses affects 1% of fertile couples. Most women have recurrent early loss with a failure of development before 10 weeks' gestation. Standard investigations fail to reveal any apparent cause in \>50% of couples. No study has demonstrated any benefit of any medication in women with Unexplained RM, in the presence or absence of an inherited thrombophilia. Moreover, the benefit of aspirin and/or heparin has not been proved in women with Antiphospholipid (APL) antibody without other clinical manifestations of Antiphospholipid Syndrome. Hydroxychloroquine (HQ) is a molecule whose properties (anti-thrombotic, vascular-protective, immunomodulatory, improved glucose tolerance, lipid-lowering, anti-infectious) could be useful against mechanisms of Unexplained RM. There is no data concerning the benefit of HQ in RM in the presence or absence of antiphospholipid antibodies or any inherited thrombophilia. Administration in (Systemic Lupus erythematosus (SLE) women and for Malaria prevention provides extensive safety data during pregnancy. Oral administration makes possible treatment since the preconception period. For all of that and its low cost, hydroxychloroquine should be evaluated in RM whatever the woman thrombophilic status.

Conditions

Recurrent Miscarriage; First Trimester Abortion

Keywords

Unexplained Recurrent Miscarriage; First trimester abortion; Hydroxychloroquine; Antiphospholipid antibody

Outcome Measures

Primary Outcomes (1)

• A live and viable birth

  In case of preterm and/or low birth weight, we define the viability by the decision to transfer the newborn to a neonatal intensive care unit

  At delivery

Secondary Outcomes (13)

• a live and viable birth (for the subgroup analyses)

  At delivery

• occurrence of pregnancy complications (Recurrent Miscarriage-any other premature termination of pregnancy-placental vascular disease)

  Since the beginning of pregnancy up to delivery

• gestation time (in weeks of amenorrhea) at delivery,

  At delivery up

• birth weight (in grams) at delivery

  At delivery

• survival of the newborn

  At 28 days of the newborn

Study Arms (2)

Hydroxychloroquine

EXPERIMENTAL

The treatment will be orally administrated, at a daily dose of 400 mg of hydroxychloroquine . The treatment will be started before conception and will be stopped at the end of the tenth week of gestation or before in case of pregnancy loss.

Drug: Hydroxychloroquine

Placebo

PLACEBO COMPARATOR

A similar placebo will be orally administrated every day.

Drug: Placebo

Interventions

Hydroxychloroquine DRUG

Hydroxychloroquine : 200 mg twice a day

Hydroxychloroquine

Placebo DRUG

placebo of hydroxychloroquine

Placebo

Eligibility Criteria

• Age: 18 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• women aged from 18 to 38 years,
• women trying to conceive,
• women with at least 3 previous consecutive miscarriage in the first pregnancy trimester, of unknown origin (normal parental karyotypes, no uterine cavity abnormality, no antiphospholipid syndrome with other clinical events than RM in the first trimester of pregnancy.)
• women who have given their informed consent

You may not qualify if:

• ongoing pregnancy,
• Normal pregnancy since the last miscarriage,
• Uterine cavity abnormality,
• Abnormal parental karyotype,
• Antiphospholipid syndrome defined as both persistent positive antiphospholipid antibodies (40 IU or more of anticardiolipin or anti beta2 GPI IgG or IgM, and/or lupus anticoagulant) and a specific clinical setting (thrombotic or obstetrical, apart from RM)
• women with a contraindication or an indication to a treatment by hydroxychloroquine
• Previous exposure \> 4 years to chloroquine or hydroxychloroquine
• impossible follow up

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (18)

Centre Hospitalier Annecy Genevois

Annecy, 74374, France

Location

CH d'Auch

Auch, 32008, France

Location

CHU Besançon

Besançon, 25030, France

Location

CHRU de Brest

Brest, 29609, France

Location

CHU Estaing

Clermont-Ferrand, France

Location

CHRU de Lille

Lille, 59037, France

Location

Hôpital Nord - Unité mère-enfant

Marseille, 13015, France

Location

CH de Mont de Marsan

Mont-de-Marsan, 40000, France

Location

CHU de Nantes

Nantes, 44093, France

Location

Hopital Saint Antoine

Paris, 75012, France

Location

Hôpital Bichat

Paris, 75018, France

Location

Hopital Port Royal Cochin

Paris, 75679, France

Location

CHG François Mitterand

Pau, 64 000, France

Location

Centre hospitalier de Cornouaille

Quimper, 29000, France

Location

Hôpital sud de Rennes

Rennes, 35200, France

Location

CHU de Saint Etienne - Hôpital Nord

Saint-Etienne, 42 270, France

Location

Nouvel Hôpital Civil

Strasbourg, 67091, France

Location

CH de Bigorre

Tarbes, 65013, France

Location

Related Publications (1)

• Pasquier E, de Saint-Martin L, Marhic G, Chauleur C, Bohec C, Bretelle F, Lejeune-Saada V, Hannigsberg J, Plu-Bureau G, Cogulet V, Merviel P, Mottier D. Hydroxychloroquine for prevention of recurrent miscarriage: study protocol for a multicentre randomised placebo-controlled trial BBQ study. BMJ Open. 2019 Mar 20;9(3):e025649. doi: 10.1136/bmjopen-2018-025649.

  PMID: 30898821 DERIVED

MeSH Terms

Conditions

Abortion, Habitual

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Abortion, Spontaneous; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Elisabeth PASQUIER, MD

  EA3878 - University Hospital of Brest

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Active drug and placebo will be exactly the same
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double Blind Randomized clinical trial

Study Record Dates

• First Submitted: May 3, 2017
• First Posted: May 24, 2017
• Study Start: December 4, 2017
• Primary Completion: November 1, 2025
• Study Completion: February 1, 2026
• Last Updated: October 2, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (18)