Prednisolone Administration in Patients With Unexplained REcurrent MIscarriages

NCT05725512 | Recruiting Phase 4 DMC

• 1 other identifier: LUMC-PREMI
• Study Type: interventional
• Target: 490
• Locations: 1 country
• Sites: 1

Brief Summary

Recurrent miscarriages (RM) affects 3% of all fertile couples, but remains unexplained in most cases, limiting therapeutic options. Possibly the maternal immune system plays a role in recurrent miscarriage. Prednisolone suppresses the immune system and might enable development of normal pregnancy. In this randomized controlled clinical trial the investigators will study the effect of prednisolone on the live birth rate in patients with RM. Secondary, the tolerability and safety for mother and child and the cost-effectiveness is investigated. In the study one group of pregnant women with RM and gestational age \<7 weeks will receive prednisolone, the other group will receive a placebo. Total use of the medicine during this study is 8 weeks, further care during the study is routinely antenatal care. Subjects will be asked to fill in 4 short questionnaires and will have contact with a research nurse at different time points to gain information on the course of the pregnancy and possible side effects. Results of the study will be implemented in (inter) national guidelines, to effect everyday practice.

Conditions

Recurrent Miscarriage; Recurrent Pregnancy Loss; Habitual Abortion; Miscarriage; Fertility Disorders

Keywords

Recurrent pregnancy loss; Recurrent miscarriage; prednisolone

Outcome Measures

Primary Outcomes (1)

• Live birth rate

  Birth of a living child beyond 24 weeks

  Within 24 months after eligibility

Secondary Outcomes (12)

• Ongoing pregnancy

  At +/- 12 weeks of pregnancy

• Congenital abnormalities

  At or short after birth, within 24 months after eligibility

• Gestational age

  After birth, within 24 months after eligibility

• Survival at 28 days of neonatal life

  28 days postpartum

• Adverse events

  From start intervention until stop intervention (maximum of 7 weeks)

Other Outcomes (1)

• Level of immune cells post intervention

  After miscarriage or delivery, within 24 months after eligibility

Study Arms (2)

Prednisolone

EXPERIMENTAL

Prednisolone tablets (20 mg daily for 6 weeks, 10 mg daily for 1 week, 5 mg daily for 1 week)

Drug: Prednisolone

Placebo

PLACEBO COMPARATOR

Identical placebo tablets for 8 weeks

Drug: Placebo

Interventions

Prednisolone DRUG

Prednisolone tablets (20 mg daily for 6 weeks, 10 mg daily for 1 week, 5 mg daily for 1 week) or identical placebo tablets for 8 weeks

Prednisolone

Placebo DRUG

Placebo identical to prednisolone tablets

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Amsterdam University Medical Center: collaborator
• Erasmus Medical Center: collaborator
• Academisch Ziekenhuis Groningen: collaborator
• Maastricht University Medical Center: collaborator
• Isala: collaborator
• Catharina Ziekenhuis Eindhoven: collaborator
• Haaglanden Medical Centre: collaborator
• Amphia Hospital: collaborator
• Radboud University Medical Center: collaborator
• Jeroen Bosch Ziekenhuis: collaborator
• Onze Lieve Vrouwe Gasthuis: collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 233ZA, Netherlands

RECRUITING

Related Publications (1)

• Bequet Y, van der Hoorn ML, Eikmans M, Van der Molen R, le Cessie S, van Geloven N, van den Akker-van Marle E, Vermeulen M, van den Berg M, de Bruin JP, Cantineau A, Huppelschoten D, Meuleman T, Mulders A, Al-Nasiry S, Teklenburg G, Verhoeve H, Visser J, van der Zanden M, Goddijn M, Lashley E. Effect of prednisolone on live birth rate in women with unexplained recurrent pregnancy loss: a study protocol for a double-blind, placebo-controlled, multicentre, randomised controlled trial (PREMI-study). BMJ Open. 2025 Jun 19;15(6):e096545. doi: 10.1136/bmjopen-2024-096545.

  PMID: 40537239 DERIVED

MeSH Terms

Conditions

Abortion, Habitual; Abortion, Spontaneous

Interventions

Prednisolone

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

Eileen Lashley, PhD

CONTACT

0031-715263362; e.e.l.o.lashley@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: None of the personnel with patient contact will have knowledge to the patient's allocation to prednisolone or placebo group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle investigator

Study Record Dates

• First Submitted: January 19, 2023
• First Posted: February 13, 2023
• Study Start: January 29, 2024
• Primary Completion (Estimated): July 29, 2026
• Study Completion (Estimated): July 29, 2027
• Last Updated: May 24, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After results have been published in a manuscript.
• Access Criteria: If informed consent of participants is available, individual data on above mentioned co-variates will be shared for IPD meta-analysis. Sharing will be done after publication and will be available up to 5 years after study has ended. Study protocol will be available too. Data will only be shared with researchers with a methodologically sound proposal directed to e.e.l.o.lashley@lumc.nl. To gain access, data requestors will need to sign a data access agreement.

Locations

NL (1)