Hydroxychloroquine for Prevention of Recurrent Miscarriage. (BBQ)
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|ClinicalTrials.gov Identifier: NCT03165136|
Recruitment Status : Recruiting
First Posted : May 24, 2017
Last Update Posted : June 17, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Miscarriage First Trimester Abortion||Drug: Hydroxychloroquine Drug: Placebo||Phase 3|
Regarding the mechanisms of unexplained RM, on the basis of animal models and clinical studies, many hypotheses were raised:
- Reduced ovarian reserve,
- Progesterone defect: a double-blind trial did not show any benefit of progesterone therapy.
- Thrombotic mechanisms and/or endothelial dysfunction: An association with some inherited thrombophilias was suggested. A prothrombotic state outside of pregnancy was measured in women with previous RM and without known thrombophilia.
- Immunological disturbances (high titers of anti-thyroid or APL antibodies, maternal carriage of specific HLA alleles and immunological reactions against male-specific minor antigens, increased numbers of peripheral blood natural killer, overexpression of TOLL receptors, increase of TH1 and TH17 processes). Consequently, immunomodulatory treatments were proposed and assessed (no impact of intravenous immunoglobulins and no conclusive benefit of corticosteroids).
- Miscellaneous: BMI> 30 and chronic endometritis. Besides, the experience gained from previous clinical trials in RM leads us to emphasize, that subcutaneous administration of heparin limits its assessment among fertile women. Indeed, the treatment could not be administrated before conception and consequently the exposure was often too short (injections cannot be routinely initiated before 5 weeks).
Except psychological support, there is no treatment whose benefit has been proved in unexplained RM, in the presence or in the absence of an inherited thrombophilia. Moreover the absence of benefit of some treatments has been clearly demonstrated. Although the prognostic is not so poor (live-birth rates around 70%), proposed therapeutic interventions are sometimes excessive (regarding possible side effects and cost): as intravenous immunoglobulins, assisted procreation ...anti-TNF.
Consequently, for the management of these distressed patients, investigating other therapeutic options is highly needed.
Regarding recurrent miscarriage in women with high titers of antiphospholipid but without any other previous clinical event listed in the antiphospholipid syndrome, the benefit of antithrombotic treatment remains controversial (negative results of the HepASA trial) and hydroxychloroquine has never been assessed, although retrospective studies are encouraging.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||300 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Double Blind Randomized clinical trial|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Active drug and placebo will be exactly the same|
|Official Title:||Prévention Des Fausses Couches Spontanées Répétées Par Hydroxychloroquine. Essai thérapeutique Multicentrique, randomisé, en Double Insu, Contre Placebo|
|Actual Study Start Date :||December 4, 2017|
|Estimated Primary Completion Date :||November 1, 2023|
|Estimated Study Completion Date :||February 1, 2024|
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.
Hydroxychloroquine : 200 mg twice a day
Placebo Comparator: Placebo
A similar placebo will be orally administrated every day.
placebo of hydroxychloroquine
- A live and viable birth [ Time Frame: At delivery ]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
- a live and viable birth (for the subgroup analyses) [ Time Frame: At delivery ]
- occurrence of pregnancy complications (Recurrent Miscarriage-any other premature termination of pregnancy-placental vascular disease) [ Time Frame: Since the beginning of pregnancy up to delivery ]
- gestation time (in weeks of amenorrhea) at delivery, [ Time Frame: At delivery up ]
- birth weight (in grams) at delivery [ Time Frame: At delivery ]
- survival of the newborn [ Time Frame: At 28 days of the newborn ]
- psychomotor development of the child (normal/abnormal) [ Time Frame: at 6 months of age ]
- psychomotor development of the child (normal/abnormal) [ Time Frame: at 12 months of age ]
- height (in centimeters) [ Time Frame: at 6 months of age ]
- height (in centimeters) [ Time Frame: at 12 months of age ]
- weight (in grams) [ Time Frame: at 6 months of age ]
- weight (in grams) [ Time Frame: at 12 months of age ]
- Cranial perimeter (in centimeters) [ Time Frame: at 6 months of age ]
- Cranial perimeter (in centimeters) [ Time Frame: at 12 months of age ]
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): NCT03165136
|Contact: Elisabeth PASQUIER, MDemail@example.com|
|Contact: Gisèle MARHIC, Ingfirstname.lastname@example.org|
|Auch, France, 32008|
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|Besançon, France, 25030|
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|CHRU de Brest||Recruiting|
|Brest, France, 29609|
|Contact: Elisabeth PASQUIER email@example.com|
|Contact: Gisèle MARHIC firstname.lastname@example.org|
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|Hôpital Nord - Unité mère-enfant||Recruiting|
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|CH de Bigorre||Recruiting|
|Tarbes, France, 65013|
|Contact: Giulia Mencattini firstname.lastname@example.org|
|Principal Investigator:||Elisabeth PASQUIER, MD||EA3878 - University Hospital of Brest|