Hydroxychloroquine (HCQ) for Recurrent Pregnancy Loss

Study Overview
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Brief Summary
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Recurrent pregnancy loss (RPL) defined as 3 or more pregnancy losses affects approximately 3% of couples trying to achieve parenthood. Most cases of RPL are unexplained and have no effective treatment to improve the chance of a live birth. Exciting indications for using Hydroxychloroquine (HCQ) include: Malaria profylaxis and treatment, systemic and discoid lupus erythematosus (SLE) and rheumatoid athritis (RA). HCQ has been reported to have the following properties (anti-thrombotic, vascular-protective, immunomodulatory, improving glucose tolerance, lipid-lowering, and anti-infectious). There is no data concerning the benefit of HCQ in RPL. Administration for other indications provides extensive safety data during pregnancy. This study has the potential to establish support for a new treatment option for unexplained RPL.

Official Title
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Hydroxycloroquin (Plaquenil) Behandling af Gentagne Graviditetstab (Abortus Habitualis) - et Randomiseret, Dobbeltblindet, Placebo Kontrolleret Studium

Conditions
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Recurrent Pregnancy Loss

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Hydroxychloroquine placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 4 confirmed consecutive pregnancy losses prior to gestational age 22+0 in women with unexplained RPL ≥ 3 confirmed consecutive pregnancy losses prior to gestational age 22+0 in women with unexplained RPL with minimum one second trimester loss. Exclusion Criteria: Age below 18 years or above 39 at inclusion Abnomal uterine anatomi at hysterosalpingography/hysteroscopy or hydrosonography Chromosomal abnormalities within the couple Menstrual cycle below 23 days or above 35 days Lupusantikoagulans positivity or immunoglobulin (Ig)G/IgM anticardiolipinantibodies (≥10 GPL kU/l at Rigshospitalets Laboratorium) or plasma homocystein ≥25 mikrogr./l at repeated measurement with 12 weeks interval. HIV or Hepatitis B or C positive Psoriasis, retinopathy og serious imparied hearing (Contraindications for HCQ) Chronic disease that lead to intake of immunemodulatory drugs or potentially pregnancy toxic agents Hemoglobin ≤ 6.5 mmol/L, leukocytes <3.5 E9/L, platelets <145 E9/L at inclusion Previous treatment with HCQ in pregnancy >1previous live birth previous participation in this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychlorochine HCQ<br>Women in the experimental arm will take 200 mg HCQ tablets every day, starting minimum 2 months (recommended 3-6) prior to conception and continuing until 28 weeks of pregnancy or until the pregnancy is over. | Drug: Hydroxychloroquine<br>* One tablet a day from inclusion until end of pregnancy or gestational age 28<br>* Other names: Placebo;|
| Placebo Comparator: Hydroxychlorochine HCQ Placebo<br>Women in the experimental arm will take 200 mg HCQ placebo tablets every day, starting minimum 2 months (recommended 3-6) prior to conception and continuing until 28 weeks of pregnancy or until the pregnancy is over. | Drug: Hydroxychloroquine placebo<br>* One tablet a day from inclusion until end of pregnancy or gestational age 28<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth |  | At delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth after exclusion of patients with a chromosomal abnormal pregnancy loss, extrauterine pregnancy loss, intended abortion or patients with insufficient intake of study medicine |  | At delivery | 
| Birth weight |  | At delivery | 
| Gestational age |  | up to at delivery | 
| Admittance to neonatal unit |  | Within 28 days of delivery | 
| Immunological status | Measuements of celllur and humoral immunity | Up to two years after end of study |