Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03165136 |
| Other study ID # |
29BRC16.0045 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
December 4, 2017 |
| Est. completion date |
February 1, 2026 |
Study information
| Verified date |
September 2023 |
| Source |
University Hospital, Brest |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
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.
