Synbiotics in Patients at RIsk fOr Preterm Birth

Not Applicable

Recruiting

• Conditions: Microbial Colonization; Preterm Spontaneous Labor With Preterm Delivery; Preterm Birth
• Interventions: Other: Synbiotics; Other: Placebo

• Registration Number: NCT05966649
• Lead Sponsor: Ziekenhuis Oost-Limburg

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-02
• Study Start: 2023-03-16
• Status Verified: 2023-06
• Study First Submitted QC: 2023-07-25
• Study First Posted: 2023-07-28
• Last Update Submitted: 2024-06-11
• Last Update Posted: 2024-06-13
• Primary Completion: 2027-12
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 402

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Synbiotics	Synbiotics	Oral synbiotic (food supplement) containing 8 probiotic Lactobacillus strains, the prebiotics inulin, fructooligosaccharides (FOS) and D-mannose.
Placebo	Placebo	Matching placebo

Primary Outcome Measures

Name	Time	Method
Gestational age at delivery	Through study completion - at delivery

Secondary Outcome Measures

Name	Time	Method
Incidence of PTB, defined as GA at delivery < 37 weeks	Through study completion - at delivery
Composition of the vaginal microbiome	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)	The vaginal microbiome will be assessed throughout pregnancy at 4 well-defined stages of pregnancy (9, 20, 30 weeks and at delivery) and at admission at the MIC unit for preterm labor, PPROM or cervical insufficiency.
Incidence of neonatal admissions	Neonatal admission at a neonatal intensive care unit (when the neonate is admitted at a neonatal intensive care unit within 7 days of delivery)
Duration of neonatal admissions	Neonatal admission at a neonatal intensive care unit (when the neonate is admitted at a neonatal intensive care unit within 7 days of delivery)
Incidence of maternal admissions	Up to 34 weeks from the date of randomization
Neonatal outcome: bronchopulmonary dysplasia (BPD)	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)	Proportion of each category (no, mild, moderate and severe)
Neonatal outcome: intraventricular haemorrhage	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)	Incidence
Neonatal outcome: respiratory support	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)	Need for respiratory support (CPAP: continuous positive airways pressure, non-invasive positive pressure ventilation or mechanical endotracheal ventilation) and the duration of respiratory support in days. Use and administration of surfactant
Neonatal outcome: retinopathy	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)	Incidence
Neonatal outcome: birth weight	After the neonate is born
PPROM	Up to 34 weeks from the date of randomization	Time to delivery
Proportion of PTB in different categories	Through study completion - at delivery	* of patients that deliver \< 28 weeks: extreme PTB; * of patients that deliver from 28 until 37 weeks: very PTB; * of patients that deliver from 32 until 37 weeks: moderate to late PTB
Neonatal outcome: periventricular leukomalacia	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)	Incidence
Duration of maternal admissions	Up to 34 weeks from the date of randomization
Quality Of Life during pregnancy and during neonatal admission at a neonatal intensive care unit	Trough study completion, on average 1 year	Using EQ5D questionnaire (5 questions and scale from 1 to 100)
Neonatal outcome: infectious parameters	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)	Sepsis (early, late and culture negative), number of episodes (min 72 hours) of antibiotic treatment, duration of antibiotic treatment in days
Neonatal outcome: neonatal morbidity	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)	Incidence

Trial Locations

Locations (7)

Universitaire Ziekenhuizen Leuven; 🇧🇪 Leuven, Limburg, Belgium

AZ Groeninge; 🇧🇪 Kortrijk, Belgium

Ziekenhuis Oost-Limburg; 🇧🇪 Genk, Limburg, Belgium

UZ Gent; 🇧🇪 Gent, Oost-Vlaanderen, Belgium

AZ Sint-Lucas; 🇧🇪 Brugge, West-Vlaanderen, Belgium

CHR Citadelle; 🇧🇪 Liège, Belgium

AZ Sint-Jan; 🇧🇪 Brugge, West-Vlaanderen, Belgium