Prednisolone Administration in Patients With Unexplained REcurrent MIscarriages

Launched by LEIDEN UNIVERSITY MEDICAL CENTER · Feb 2, 2023

Keywords

ClinConnect Summary

This clinical trial is studying whether a medication called prednisolone can help women who have experienced unexplained recurrent miscarriages achieve a live birth. Recurrent miscarriages affect about 3% of couples trying to conceive, and in many cases, the reasons for these losses are unknown. Prednisolone works by suppressing the immune system, which some believe may help support a healthy pregnancy. In this study, pregnant women who have had multiple miscarriages and are less than 7 weeks along will be randomly assigned to receive either prednisolone or a placebo (a harmless pill with no active ingredients) for 8 weeks.

To participate, women need to be between 18 and 39 years old, have had at least two miscarriages without any known medical causes, and be able to confirm their pregnancy with a test. Throughout the study, participants will have routine prenatal care, complete a few brief questionnaires, and have regular check-ins with a research nurse to monitor their pregnancy and any side effects. The findings from this trial could influence future guidelines and recommendations for managing recurrent miscarriages, so participation may help improve care for others in similar situations.

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• • Unexplained recurrent pregnancy loss: defined as the loss of ≥2 pregnancies, without any known cause for RM (parental chromosomal abnormalities, uterine anomalies, acquired or hereditary thrombophilia, endocrine diseases (such as hypothyroidism or diabetes)).
• * The miscarriages include:
• • all consecutive or non-consecutive pregnancy losses before the 24th week of gestation verified by ultrasonography or uterine curettage and histology
• • non-visualized pregnancies (including biochemical pregnancy losses and/or resolved and treated pregnancies of unknown location), verified by positive urine or serum hCG Ectopic and molar pregnancies are not included
• • Age 18 - 39 years at randomization (likelihood of miscarriages due to chromosomal aberrations is higher when age \> 39 years. Such miscarriages are unlikely to be pre-vented by prednisolone therapy)
• • Conception confirmed by urinary pregnancy test, with estimated gestational age ≤ 7weeks
• • Willing and able to give informed consent in English or Dutch (IC)
• Exclusion Criteria:
• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• • Any of the following diagnosis for the recurrent miscarriages
• • Antiphospholipid syndrome (lupus anticoagulant and/ or anticardiolipin anti-bodies and/or beta-2 glycoprotein \[IgG or IgM)
• • Congenital uterine abnormalities (as assessed by 2D or 3d ultrasound, hys-terosonography, hysterosalpingogram or hysteroscopy)
• • Abnormal parental karyotype
• • Instable or exacerbation of auto-immune diseases such as diabetes, thyroid disease, inflammatory bowel diseases or SLE
• • Inability to conceive within 1 year of recruitment
• • Current treatment with systemic prednisolone or other immune suppressive medication (for any indication)
• • Previous enrolment in the PREMI trial
• • Enrolment in any other trial that studies the effectiveness of an intervention on RM
• * Contraindications to prednisolone use:
• • Known allergy for prednisolone
• • Acute bacterial infection or parasite infection
• • Active COVID infection
• • Systemic sclerosis
• • Ulcus ventriculi or ulcus duodeni in medical history
• • Obesity with BMI \>40
• * Some drugs are known to interact with Prednisolone, and thus women on the following drugs are not eligible to take part in the PREMI trial:
• • Enzyme inducers, such as carbamazepine, fenobarbital, fenytoïne and ri-fampicine
• • CYP3A inhibitors, such as Cobicistat or Ritonavir
• • Cyclosporine
• • Digoxin
• • Vaccination (with inactivated virus or bacteria) during prednisolone use is possibly less effective