Vaginal Probiotics During Pregnancy After Premature (24-32 Weeks of Gestation) Preterm Rupture of Membranes (PROB-PROM)

Multicentric Clinical Pilot Trial Testing the Association Between Antibiotics and Vaginal Probiotics for Patients With Prematured Rupture of Membranes Between 24 and 32 Weeks of Amenorrhea ( PROB-PROM Study)

The goal of this clinical trial is to evaluate the feasibility of the randomized controlled trial (RCT).

Secondary objectives include comparing the microbiota of preterm babies born after premature rupture of membranes across study groups.

To achieve this, participants will be asked to:

• Use the vaginal study product from the time of membrane rupture until delivery
• Keep a diary documenting their symptoms and treatment adherence
• Provide vaginal secretion samples and stool samples from their baby

Study Overview

• Status: Not yet recruiting
• Conditions: Pregnancy; Prematurity; PPROM
• Intervention / Treatment: Other: Probiotic; Other: Placebo

Detailed Description

Premature rupture of fetal membranes before labor (PPROM) accounts for 30% of preterm births. Since PPROM is strongly associated with ascending vaginal infection, antibiotics are recommended during the latent period (LP) (the interval between rupture and birth). While they prolong the LP and improve neonatal health, they also exacerbate pre-existing vaginal dysbiosis. The addition of vaginal probiotics (VP) helps stabilize the vaginal microbiota (VM) and increase Lactobacillus levels. By enhancing the presence of beneficial bacteria in the vagina, probiotics help restore the balance between beneficial and pathogenic microbes, potentially reducing uterine infection and improving the fetal intestinal microbiota.

Pathophysiological Hypotheses for Improving Neonatal Health

The use of VP may influence neonatal outcomes through three potential mechanisms:

i) Reduction of vaginal dysbiosis: Prolongs pregnancy and mitigates complications related to fetal immaturity (e.g., decreases risk of intraventricular hemorrhage).

ii) Reduction of intrauterine infection/inflammation: Lowers neonatal complications associated with inflammation (e.g., reduces incidence of cystic periventricular leukomalacia).

iii) Improvement of neonatal intestinal microbiota (NIM) through probiotic ingestion: Decreases complications linked to neonatal dysbiosis (e.g., reduces risk of necrotizing enterocolitis [NEC]).

Primary Objectives

• To assess the validity of:

  i) A recruitment rate > 35% ii) A treatment adherence rate > 80% iii) A sample attrition rate < 5%

• To identify barriers and facilitators in different settings for the implementation of the randomized controlled trial (RCT).

Secondary Objectives

• To compare the presence of probiotics in the vaginal microbiota and neonatal stool (meconium and at 7 days of life).
• To measure the effect of probiotics on the evolution of maternal vaginal microbiota and neonatal intestinal microbiota.

Population Pregnant women aged 18 years or older giving birth at one of the eight centers participating in the study in Quebec and Ontario, Canada. Participants will be randomly assigned, in a blinded manner, to either the probiotic or placebo group.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jean-Charles Pasquier; Phone Number: 819-679-2212; Email: jean-charles.pasquier@umontreal.ca
• Study Contact Backup: Name: Sarah Bilodeau; Phone Number: 30620 514-890-8000; Email: sarah.bilodeau.chum@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre de Recherche du CHUM
      • Principal Investigator: Jean-Charles Pasquier
      • Contact: Sarah Bilodeau; Phone Number: 30620 514-890-8000; Email: sarah.bilodeau.chum@ssss.gouv.qc.ca
      • Contact: Bilodeau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• women ≥ 18 years of age;
• mono-fetal pregnancy;
• treated for PPROM between 24 and 32 weeks of gestation with latency period between 12 hours and < 7 days in one of the study centers with expectant management;
• speaking and able to read French or English.

Exclusion Criteria:

• Presence of active labor;
• Situation contraindicating expectant management (e.g., infection);
• Significant malformation, chromosomal anomaly, or fetal death;
• Signs of fetal distress;
• Allergy or intolerance to any of the following substances: vitamin C (ascorbic acid), magnesium stearate, maltodextrin, gelatin, yeast, sucrose, trehalose;
• Allergy to soy or lactose;
• Weakened immune system (e.g., AIDS, prolonged corticosteroid treatment, etc.);
• Vaginal probiotics intake 15 days before study inclusion;
• Oral probiotic intake 30 days before study inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Probiotics group; Probiotics is a mix of probiotic strains.	Other: Probiotic; Participant will take 1 intravaginal capsule once a day at bedtime between inclusion in the study until delivery
Placebo Comparator: Placebo group; Capsule of sugar, same appearance than the probiotic.	Other: Placebo; Participant will take 1 intravaginal capsule once a day at bedtime between inclusion in the study until delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	To assess the feasibility of the study, each local site team will complete a dashboard documenting every individual met and informed about the study. This dashboard will be used to calculate the recruitment rate, using the formula: Recruitment rate = (Number of eligible patients - Number of patients who did not consent) / Number of eligible patients Additionally, the dashboard will track reasons for acceptance or refusal.	7 months
Feasability dashboard	The attrition rate will be explored to assess feasability of the study. Attrititon rate = (# participants who dropped out / total of participants).	7 months
Treatment adherence	Finally, number of caps took during the treatment phase will be reported to explore the adherence of treatment.	7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probiotics primers	Evaluate the presence or absence of probiotics in the various samples, i.e. vaginal secretions, meconium and 7-day-old baby's stool, using specific primers to detect strains.	From enrollement to infant 7th day of life

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Lallemand Health Solutions, Canada

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: April 14, 2025
• First Submitted That Met QC Criteria: May 1, 2025
• First Posted (Actual): May 11, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2025
• Last Update Submitted That Met QC Criteria: May 1, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: pregnancy; prematurity; microbiota; PPROM; vaginal probiotics
• Additional Relevant MeSH Terms: Urogenital Diseases; Wounds and Injuries; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth; Rupture
• Other Study ID Numbers: MP-02-2025-12882

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Protocol, Statistical Analysis Plan (SAP) and informed Consent Form (ICF). No data concerning individual participant will be shared or published.
• IPD Sharing Time Frame: The supporting information will be shared before the end of the study.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No