Clinical trial NCT05966649: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Preterm Spontaneous Labor With Preterm Delivery
Preterm Birth
Microbial Colonization
Keywords: Preterm birth
Vaginal microbiome
Probiotics
Synbiotics
Lead sponsor: Ziekenhuis Oost-Limburg
Sponsor class: OTHER
First posted: 2023-07-28
Enrollment: 402
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Signed written informed consent must be obtained before any study assessment is performed;
2. 18 years of age or older;
3. Singleton pregnancy;
4. Pregnancy consultation between 8 and 10 weeks gestation.
5. 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:

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

Primary outcomes:
measure: Gestational age at delivery
timeFrame: Through study completion - at delivery
Secondary outcomes:
measure: Incidence of PTB, defined as GA at delivery < 37 weeks
timeFrame: Through study completion - at delivery
measure: Proportion of PTB in different categories
timeFrame: Through study completion - at delivery
measure: PPROM
timeFrame: Up to 34 weeks from the date of randomization
measure: PPROM
timeFrame: Up to 34 weeks from the date of randomization
measure: PPROM
timeFrame: Up to 34 weeks from the date of randomization
measure: Composition of the vaginal microbiome
timeFrame: 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)
measure: Incidence of neonatal admissions
timeFrame: Neonatal admission at a neonatal intensive care unit (when the neonate is admitted at a neonatal intensive care unit within 7 days of delivery)
measure: Duration of neonatal admissions
timeFrame: Neonatal admission at a neonatal intensive care unit (when the neonate is admitted at a neonatal intensive care unit within 7 days of delivery)
measure: Incidence of maternal admissions
timeFrame: Up to 34 weeks from the date of randomization
measure: Duration of maternal admissions
timeFrame: Up to 34 weeks from the date of randomization
measure: Quality Of Life during pregnancy and during neonatal admission at a neonatal intensive care unit
timeFrame: Trough study completion, on average 1 year
measure: Neonatal outcome: infectious parameters
timeFrame: 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)
measure: Neonatal outcome: bronchopulmonary dysplasia (BPD)
timeFrame: 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)
measure: Neonatal outcome: intraventricular haemorrhage
timeFrame: 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)
measure: Neonatal outcome: periventricular leukomalacia
timeFrame: 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)
measure: Neonatal outcome: respiratory support
timeFrame: 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)
measure: Neonatal outcome: retinopathy
timeFrame: 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)
measure: Neonatal outcome: neonatal morbidity
timeFrame: 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)
measure: Neonatal outcome: birth weight
timeFrame: After the neonate is born
Other outcomes:
measure: Effect of antibiotics on the vaginal microbiome
timeFrame: During pregnancy until 28 days after PPROM
measure: Effect on the gastrointestinal microbiome of the neonate in case of PPROM
timeFrame: Between 13 to 36 weeks from the date of randomization
measure: Placental microbiome in case of preterm birth
timeFrame: Between 13 to 36 weeks from the date of randomization
Locations:
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
state: Limburg
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
state: Limburg
city: Gent
country: Belgium
facility: UZ Gent
state: Oost-Vlaanderen
city: Brugge
country: Belgium
facility: AZ Sint-Jan
state: West-Vlaanderen
city: Brugge
country: Belgium
facility: AZ Sint-Lucas
state: West-Vlaanderen
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Liège
country: Belgium
facility: CHR Citadelle
Study officials:
References: