A multi-center, randomized, placebo-controlled trial is currently being conducted to evaluate the potential of synbiotic supplementation in preventing spontaneous preterm birth (sPTB) among at-risk pregnant women. The study, known as the PRIORI trial, is taking place across seven teaching hospitals in Belgium.
The trial design involves randomizing pregnant women between 80/7 and 106/7 weeks of gestation into either an intervention group receiving a daily oral synbiotic or a control group receiving a placebo. All participants will receive standard care, including vaginal progesterone and serial cervical length measurements, as deemed necessary.
The synbiotic formulation includes eight probiotic Lactobacillus strains, totaling 2 × 10^10 colony-forming units (CFU) per daily dose, along with the prebiotics inulin, fructooligosaccharides (FOS), and D-mannose. Enteric-coated capsules are used for both the synbiotic and placebo to ensure delayed release. Participants will take two capsules daily, one in the morning and one in the evening, until delivery.
The primary outcome of the trial is the gestational age at delivery, measured in weeks plus days. Secondary outcomes include preterm birth rates in various gestational age subcategories (extreme, severe, and moderate to late PTB), preterm premature rupture of membranes (PPROM) rates, gestational age at PPROM, vaginal microbiome analysis, and several neonatal outcomes. Neonatal outcomes include mortality, birth weight, necrotizing enterocolitis, bronchopulmonary dysplasia, intraventricular hemorrhage, encephalopathy of prematurity, infectious parameters, respiratory support, retinopathy and duration of neonatal admission.
Vaginal microbiome analysis will be performed via bacterial culture and metataxonomic 16S rRNA gene sequencing at multiple time points during the trial to assess the impact of synbiotic supplementation on the vaginal flora. Economic impact and quality of life (QoL) will be assessed using the Work Productivity and Activity Impairment (WPAI) and EQ-5D questionnaire.
The sample size calculation requires 382 patients to detect a clinically relevant difference in pregnancy duration of 1 week between the intervention and control group, assuming a SD of 3 weeks and with an alpha of 0.05, and a power of 90%. Accounting for a 5% dropout rate, the total number of patients to be recruited is 402.
Recruitment is expected to last approximately 36 months. Participants will be given a diary to record the intake of the IP or placebo, and adherence to the intervention will be checked based on the patient’s diary entries and the number of returned, unused capsules of IP or placebo.
Standardized treatment protocols were made in collaboration with all participating centres. Recommendations were made for the use of vaginal progesterone (200 mg once daily for the indication of sPTB prevention), tocolysis, corticosteroids for foetal lung maturation, magnesium sulphate for neuroprotection, cervical cerclage or pessary placement, antifungal medication for symptomatic Candidiasis, and antibiotics for PPROM, Group B Streptococci (GBS) prophylaxis, symptomatic BV, and common sexually transmitted infections. The use of any pre-, pro-, or synbiotic other than the IP is not allowed during the study.
