Hydroxychloroquine sulfate for Recurrent pregnancy loss

Inclusion criteria

• {"criterion_text":"- ≥ 4 confirmed consecutive pregnancy losses prior to gestational age 22+0 in women with unexplained recurrent pregnancy loss (RPL)\n- ≥ 3 confirmed consecutive pregnancy losses prior to gestational age 22+0 in women with unexplained RPL with minimum one second trimester loss"}

Exclusion criteria

• {"criterion_text":"- Age < 18 years or > 40 years\n- Previous HCQ treatment in relation to conceive\n- > 1 previous live birth.\n- Previous participation in current study.\n- Prominent uterine abnormalities detected by hysterosalpingography/hysteroscopy or hydrosonography\n- Known prominent chromosome abnormalities for the couple trying to conceive\n- A menstrual cycle < 23 days or > 35 days if the pregnancy is conceived naturally. If the woman received fertility treatment the menstrual cycle has no consequence.\n- Detection of positive lupus-anticoagulant or positive IgG/IgM for anticardiolipin-antibodies (≥10 GPL kU/l, measured at the same laboratories at the Capital Region of Denmark) or plasma homocysteine ≥25 microgram/l by repeated measurements 12 weeks apart before the pregnancy.\n- Positive HIV test or test indicating chronic hepatitis B or C.\n- Psoriasis, retinopathic or serious hearing deficiency (contraindication for treatment with HCQ)\n- Current chronic disease implicating a constant consumption of immunomodulatory medicine or medicine potentially harmful to the pregnancy/embryo\n- Hgb ≤ 6.5 mmol/L, leucocytes < 3.5 E9/L, thrombocytes < 145 E9/L by the time of inclusion"}

Primary endpoints

• {"endpoint_text":"- The trial will conclude after the inclusion and follow-up (pregnancy loss or 6 months after live birth) for 186 women. Included women who become pregnant less than two months after starting the medication or do not achieve pregnancy within one year of starting the medication will be replaced 1:1 by new patients included in the trial.","definition_or_measurement_approach":"Primary endpoint measured by completion of inclusion and follow-up for 186 women; follow-up defined as occurrence of pregnancy loss or 6 months after live birth. Replacement rule: participants who become pregnant <2 months after starting medication or who do not achieve pregnancy within 1 year will be replaced 1:1."}

Other endpoints

• {"endpoint_text":"- The difference in LBR for women allocated treatment with HCQ and those allocated placebo treatment, according to the protocol. PL due to chromosome abnormalities, ectopic pregnancy, neglect of treatment, induced abortion or those who withdraw from the treatment earlier than the protocol dictates do not fall under the category of treatment failure, and these are excluded in this secondary analysis (Per protocol (PP) analysis).\n- Birth weight, duration of pregnancy, Apgar-score five minutes after birth and the number of days admitted into a neonatal department. Patients with RPL have an increased risk of preterm birth, perinatal morbidities, and low birth weight25,26. Hence, it is relevant to investigate whether treatment with HCQ can reduce these complications, or if treatment with HCQ reduces the rate of PL at the expense of an increased rate of perinatal complications. The rate of perinatal complications is compared to the placebo group in this analysis.\n- Immune and inflammatory profiles and trajectories in women treated with HCQ vs placebo and women with live birth vs another PL. Pre-pregnancy inflammatory levels will be contrasted between women treated with HCQ and placebo to identify high responders. Furthermore, repeated measures analysis enables the understanding of pregnancy-complications and identification of high-risk groups at early stages, which may benefit from treatment.\n- Monitoring metabolic activity measured by ultra-low dose FDG-PET/CT scans in a sub-study. Metabolic activity correlates with grade of inflammation and will be measured in the uterus and immune-related tissue such as bone marrow, spleen, thymus, and lymph nodes","definition_or_measurement_approach":"Secondary/exploratory endpoints include: (1) per-protocol analysis of live birth rate (LBR) excluding specified causes of pregnancy loss; (2) neonatal outcomes (birth weight, gestational duration, 5-minute Apgar, days in neonatal unit) compared between HCQ and placebo groups; (3) immune/inflammatory profiling with repeated measures to compare trajectories between treatment groups and outcomes; (4) sub-study measurement of metabolic activity by ultra-low dose FDG-PET/CT in uterus and immune tissues."}

Denmark

Earliest CTIS Part Ii Submission Date

12-07-2024

Latest Decision Or Authorization Date

25-07-2024

Processing Time Days

13

Number Of Sites

1

Number Of Participants

186

Primary sponsor

Full Name

Hvidovre Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"Sponsor duties code: 1 (as listed in sponsor thirdParties sponsorDuties)","organisation_type":"Hospital/Clinic/Other health care facility"}