Vaginal Probiotics During Pregnancy After Premature Rupture of Membranes (PROBPROM-Pilot)

Multicentric Clinical Pilot Essay Testing Association Between Antibiotics and Vaginal Probiotics for Patients With Prematured Rupture of Membranes Between 32 and 36 Weeks of Amenorrhea ( PROBPROM-Pilot Study)

The goal of this clinical trial is to compare the microbiota of preterm babies born after premature breaking water with full-term babies microbiota.

The main questions it aims to answer are:

• Is babies' microbiota differs with premature water breaking than full-term babies microbiota?
• Is vaginal probiotics given to the mother influence the baby microbiota? Researchers will compare vaginal probiotics use to no treatment to see if the babies microbiota and mother microbiota is influenced.

Participants will

• Take vaginal probiotics between premature breaking water until delivery (group A)
• Keep a diary of their symptoms and compliance to treatment (group A)
• Take samples of vaginal secretions and of baby's stool (all groups)

Study Overview

• Status: Withdrawn
• Conditions: Pregnancy; Prematurity; PPROM
• Intervention / Treatment: Other: Vaginal probiotics

Detailed Description

Premature rupture of fetal membranes before labor (PPROM) reprensents 30% of premature births. As PPROM is strongly associated with ascending vaginal infection, antibiotics are recommended during the latent period (LP) (the interval between rupture and birth). They prolong the LP and improve the health of the children, but they also aggravate pre-existing vaginal dysbiosis. The addition of vaginal probiotics (VP) stabilizes the vaginal microbiota (VM) and increases Lactobacillus levels. By increasing the number of good germs in the vagina, they will rebalance the good germs and the pathogenic germs that make their way up to the uterus. This could reduce uterine infection and improve the foetus; intestinal flora.

Pathophysiological hypotheses for improving neonatal health:

The use of VP could have three modes of action on neonatal outcome:

i) decrease vaginal dysbiosis: pregnancy prolongation and reduce fetal immaturity complications (e.g.reduce intraventricular hemorrhage); ii) Reduction of intra-uterine infection/inflammation: Reduce neonatal complications linked to inflammation (e.g. diminish cystic periventricular leukomalacia); iii) improvement of neonatal intestinal microbiota (NIM) (probiotic swallowing): reduce complications associated with neonatal dysbiosis (e.g. reduce ulcerative colitis (NEC)).

3.1 Primary objective Mechanistic proof of concept To compare the NIM of the babies of the participants after PPROM with or without probiotics compared with the NIM of the babies of the participants without PRPOM (meconium and at 7 days of life).

Secondary objectives Primary secondary objectives (Group A or B versus C)

1. To compare the VM of participants after PPROM with or without probiotics with the VM of participants without PPROM at the end of pregnancy (early latency phase).
2. Compare the VM of participants after PPROM with or without probiotics with the VM of participants without PPROM in early labor (end of latency phase).
3. To test the possibility of transmission analysis of VP in the NIM (meconium and at 7 d of life) with groups B and C: PPROM-control and control without PPROM.

Secondary clinical objectives

1. Explore recruitment (rate, reasons for acceptance and refusal, characteristics of mothers recruited), treatment adherence >80% and attrition rate <5%.
2. Test tools for sample collection, participant information and consent form.

Population:

Pregnant women aged 18 and over, giving birth at one the three centers participating in the study CHUM, CHUSJ or CHUQ (Quebec). These women will be divided into 3 groups:

• Group A: PPROM-VP Pregnant women admitted for PPROM with VP intake
• Group B: PPROM-control Pregnant women admitted for PPROM without VP intake
• Group C: term-control without PPROM Pregnant women with expected full-term deliveries, without VP intake

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H2X 0A9
      • CHUM Clinical research Centre

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Groups A and B:

Women ≥ 18 years of age, mono-fetal pregnancy, hospitalized for PPROM between 32 0/7 d and 36 0/7 d weeks of ammenorhea with LP < 7 days in one of the participating centers, with expectant management, who have consented to participate, agree to collect samples and speak French or English

Group C:

Women ≥ 18 years, mono-fetal pregnancy, expected delivery in one of the participating centers and speaking French or English

Exclusion Criteria:

• Groups A and B:
• Presence of active labor,
• Situations contraindicating expectant management (e.g. infection),
• Significant malformation, chromosomal abnormality or fetal death,
• Signs of fetal distress,
• vaginal probiotics intake 15 days before study entry.

For Group A only:

• Allergies to soy and/or milk;
• Weakened immune system (e.g. AIDS, prolonged treatment with corticosteroids),
• Not to have been treated with the following antibiotics during pregnancy: nalidixic acid (Negram) and/or cefoxitin (Mefoxin) and/or sulfamethoxazole (Bactrim).

Group C:

• History of obstetric complications (prematurity <37 weeks, diagnosed pre-eclampsia, gestational diabetes treated with insulin),
• Known obstetrical or fetal complications of the current pregnancy, such as threat of preterm delivery (premature rupture of membranes or preterm labor), chorioamnionitis, placenta previa, active vaginal bleeding, cervical cerclage, fetal distress or malformation, corticosteroid therapy,
• Risk factors for obstetrical complications during pregnancy, such as gestational diabetes, type I/II diabetes and high blood pressure (systole ≥ 140 and diastole ≥ 90),
• Antibiotics taken 15 days prior to inclusion,
• Taking probiotics 15 days prior to inclusion,
• Tested positive for Streptococcus group B during previous pregnancies (as this will require antibiotics at delivery),
• Presence of symptoms such as fever, nausea, vomiting, bloody diarrhea or severe abdominal pain.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotics group; Pregnant women admitted to one of the center participating in the essay for PPROM accepting vaginal probiotics intake and sample collection	Other: Vaginal probiotics; Probiotics from Canadian company Lallemand Health Solutions are stored at room temperature and administered vaginally.
No Intervention: Control group - PPROM; Pregnant women admitted to one of the study's centers for PPROM without vaginal probiotics intake
No Intervention: Control group- Full Term; Pregnant women with expected full-term deliveries, without vaginal probiotics intake

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probiotics primers presence	Evaluate the presence or absence of probiotics in the meconium and stools of 7-day-old babies using specific primers to detect strains	at birth and 7th day of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	To assess feasability of the study the recruitment will be explored (recruitment rate = (# of eligible patient- # of patient who didn't consent) / # of eligible patient), also, reasons for acceptance and refusal, characteristics of mothers recruited will be documented.	12 months
Numbers of mother and baby health issues	Monitor side-effects reported in the logbook and medical record, as well as clinical outcomes for mother and baby	During the enrollment until 30 days after delivery
Probiotics primers in other samples presence	Evaluate the presence or absence of probiotics in the various samples, i.e. vaginal secretions, meconium and 7-day-old baby's stools, using specific primers to detect strains, and ii) perform microbiota analysis to compare the microbiota of mothers with and without PPROM.	between the enrollment until 30 days after delivery
Attrition rate	To assess feasability of the study, the attrition rate will be explored. Attrititon rate = (# participants who dropped out / total of participants)	13 months
Treatment adherence	# of caps took during the treatment phase will be reported to explore the adherence of treatment. This will help to assess feasability of the study	13 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2025
• Primary Completion (Actual): June 17, 2025
• Study Completion (Actual): June 17, 2025

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: March 10, 2025
• First Posted (Actual): March 17, 2025

Study Record Updates

• Last Update Posted (Actual): July 4, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 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-02-2025-12298

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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