Clinical trial NCT06965049: Vaginal Probiotics During Pregnancy After Premature (24-32 Weeks of Gestation) Preterm Rupture of Membranes
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Pregnancy
Prematurity
PPROM
Keywords: pregnancy
prematurity
PPROM
vaginal probiotics
microbiota
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: Lallemand Health Solutions, Canada
First posted: 2025-05-11
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recruitment rate
timeFrame: 7 months
measure: Feasability dashboard
timeFrame: 7 months
measure: Treatment adherence
timeFrame: 7 months
Secondary outcomes:
measure: Probiotics primers
timeFrame: From enrollement to infant 7th day of life
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Centre de recherche du CHUM
state: Quebec
Study officials:
References: