Synbiotics in Patients at RIsk fOr Preterm Birth

Official title

Synbiotics in Patients at RIsk fOr Preterm Birth: a Multi-center Double-blind Randomized Placebo-controlled trIal

Overview

Prematurity remains the main cause of death and serious health problems in new-borns. Besides the need for hospitalization and medical interventions in the first weeks or months of the new-borns' life, prematurity can cause long-lasting health problems (e.g. multiple hospital admissions, developmental delay, learning difficulties, motor delay, hearing or eye problems, ...). Moreover, prematurity places an enormous economic burden on the society. Aside from the medical problems and the financial cost, the emotional stress and psychological impact on the parents, siblings and other family members should not be underestimated. Previous preterm delivery (before 37 weeks of pregnancy) increases the risk for recurrent preterm delivery in a subsequent pregnancy. Therefore, these women should be considered as 'high risk' for preterm birth. Infections ascending from the vagina may be an important cause of preterm delivery in certain cases. Some women have an abnormal vaginal microbiome and are therefore at risk for infections and preterm birth. On the other hand, the vaginal flora is more stable and resistant to infections in healthy pregnant women who deliver at term (after 37 weeks of gestation). Synbiotics are a mixture containing probiotics and prebiotics. Probiotics are living bacteria with potential beneficial effects that can be used safely in pregnancy, while prebiotics are consumed by the bacteria. It is known that probiotics, when used for a long period of time, can maintain a healthy and stable vaginal flora that may protect against infections. In this study, pregnant patients with a history of preterm birth will be included in the first trimester of pregnancy to start with synbiotics or placebo. The investigators will examine the effect of synbiotics on the vaginal flora and on the pregnancy duration. The hypothesis is that synbiotics, when started early in the pregnancy, can change the disturbed vaginal flora into a stable micro-environment.

Interventions

• Other Synbiotics
  Oral synbiotic (food supplement) containing 8 probiotic Lactobacillus strains, the prebiotics inulin, fructooligosaccharides (FOS) and D-mannose.
• Other Placebo
  Matching placebo

Primary outcome measures

• Gestational age at delivery [Time frame: Through study completion - at delivery]

Secondary outcome measures (12)

• Incidence of PTB, defined as GA at delivery < 37 weeks [Time frame: Through study completion - at delivery]
• Proportion of PTB in different categories [Time frame: Through study completion - at delivery]
• PPROM [Time frame: Up to 34 weeks from the date of randomization]
• PPROM [Time frame: Up to 34 weeks from the date of randomization]
• PPROM [Time frame: Up to 34 weeks from the date of randomization]
• Composition of the vaginal microbiome [Time frame: Assessed 3 times during the study period: at randomization, 11-13 weeks after randomization (at gestational age 19-21 weeks), and 21-23 weeks after randomization (29-31 weeks of gestation)]
• Incidence of neonatal admissions [Time frame: Neonatal admission at a neonatal intensive care unit (when the neonate is admitted at a neonatal intensive care unit within 7 days of delivery)]
• Duration of neonatal admissions [Time frame: Neonatal admission at a neonatal intensive care unit (when the neonate is admitted at a neonatal intensive care unit within 7 days of delivery)]
• Incidence of maternal admissions [Time frame: Up to 34 weeks from the date of randomization]
• Duration of maternal admissions [Time frame: Up to 34 weeks from the date of randomization]
• Quality Of Life during pregnancy and during neonatal admission at a neonatal intensive care unit [Time frame: Trough study completion, on average 1 year]
• Neonatal outcome: infectious parameters [Time frame: During the admission at the neonatal intensive care unit (when the neonate is admitted at a neonatal intensive care unit within 7 days of delivery)]

Eligibility criteria

Inclusion criteria

• Signed written informed consent must be obtained before any study assessment is performed;
• 18 years of age or older;
• Singleton pregnancy;
• Pregnancy consultation between 8 and 10 weeks gestation.
• At least one of the following risk factors for spontaneous preterm birth:

• Prior spontaneous preterm birth, defined as delivery between 24 and 36 weeks following PPROM, preterm labor or cervical insufficiency
• PPROM ≤36 weeks in previous pregnancy
• Prior spontaneous second-trimester pregnancy loss, defined as PPROM, preterm labor or cervical insufficiency with birth between 14 and 24 weeks.

Exclusion criteria

• Patients who are already using pro-, pre- or synbiotics and not willing to stop
• Multiple pregnancy
• Need for primary (type 1) cerclage
• Inflammatory bowel disease
• Known congenital uterine anomaly
• History of LLETZ conization

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Other

Study locations

Belgium · 9 centers

• Universitaire Ziekenhuis Antwerpen — Edegem
• Ziekenhuis Oost-Limburg — Genk
• Universitaire Ziekenhuizen Leuven — Leuven
• CHR Citadelle — Liège
• UZ Gent — Ghent
• AZ Sint-Jan — Bruges
• AZ Sint-Lucas — Bruges
• AZ Maria Middelares — Ghent
• … and 1 more center

Publications

• Nulens K, Papy E, Tartaglia K, Dehaene I, Logghe H, Van Keirsbilck J, Chantraine F, Masson V, Simoens E, Gysemans W, Bruckers L, Lebeer S, Allonsius CN, Oerlemans E, Steensels D, Reynders M, Timmerman D, Devlieger R, Van Holsbeke C. Synbiotics in patients at risk for spontaneous preterm birth: protocol for a multi-centre, double-blind, randomised placebo-controlled trial (PRIORI). Trials. 2024 Sep PMID 39289685

Identifiers

NCT: NCT05966649 · Z-2022080

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗