Synbiotics in Patients at RIsk fOr Preterm Birth

Preterm Birth Clinical Trial

— PRIORI  

Official title:

Synbiotics in Patients at RIsk fOr Preterm Birth: a Multi-center Double-blind Randomized Placebo-controlled trIal

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05966649
• Other study ID #: Z-2022080
• Status: Recruiting
• Phase: N/A
• Start date: March 16, 2023
• Est. completion date: June 2028

Study information

• Verified date: June 2023
• Source: Ziekenhuis Oost-Limburg
• Contact: Caroline Van Holsbeke, PhD
• Phone: 003289327521
• Email: Caroline.van.holsbeke[@]zol.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 402
• Est. completion date: June 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Microbial Colonization
• Premature Birth
• Preterm Birth
• Preterm Spontaneous Labor With Preterm Delivery

Intervention

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

Locations

Country	Name	City	State
Belgium	AZ Sint-Jan	Brugge	West-Vlaanderen
Belgium	AZ Sint-Lucas	Brugge	West-Vlaanderen
Belgium	Ziekenhuis Oost-Limburg	Genk	Limburg
Belgium	UZ Gent	Gent	Oost-Vlaanderen
Belgium	AZ Groeninge	Kortrijk
Belgium	Universitaire Ziekenhuizen Leuven	Leuven	Limburg
Belgium	CHR Citadelle	Liège

Sponsors (1)

Lead Sponsor	Collaborator
Ziekenhuis Oost-Limburg

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effect of antibiotics on the vaginal microbiome	When the patient is admitted in case the pregnancy was complicated with PPROM	During pregnancy until 28 days after PPROM
Other	Effect on the gastrointestinal microbiome of the neonate in case of PPROM	When the neonate is born after a pregnancy complicated with PPROM	Between 13 to 36 weeks from the date of randomization
Other	Placental microbiome in case of preterm birth	In case the pregnancy was complicated with preterm birth (delivery before 37 weeks of gestation)	Between 13 to 36 weeks from the date of randomization
Primary	Gestational age at delivery		Through study completion - at delivery
Secondary	Incidence of PTB, defined as GA at delivery < 37 weeks		Through study completion - at delivery
Secondary	Proportion of PTB in different categories	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	Through study completion - at delivery
Secondary	PPROM	Incidence	Up to 34 weeks from the date of randomization
Secondary	PPROM	Gestational age at PPROM	Up to 34 weeks from the date of randomization
Secondary	PPROM	Time to delivery	Up to 34 weeks from the date of randomization
Secondary	Composition of the vaginal microbiome	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.	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)
Secondary	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)
Secondary	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)
Secondary	Incidence of maternal admissions		Up to 34 weeks from the date of randomization
Secondary	Duration of maternal admissions		Up to 34 weeks from the date of randomization
Secondary	Quality Of Life during pregnancy and during neonatal admission at a neonatal intensive care unit	Using EQ5D questionnaire (5 questions and scale from 1 to 100)	Trough study completion, on average 1 year
Secondary	Neonatal outcome: infectious parameters	Sepsis (early, late and culture negative), number of episodes (min 72 hours) of antibiotic treatment, duration of antibiotic treatment in days	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)
Secondary	Neonatal outcome: bronchopulmonary dysplasia (BPD)	Proportion of each category (no, mild, moderate and severe)	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)
Secondary	Neonatal outcome: intraventricular haemorrhage	Incidence	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)
Secondary	Neonatal outcome: periventricular leukomalacia	Incidence	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)
Secondary	Neonatal outcome: respiratory support	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	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)
Secondary	Neonatal outcome: retinopathy	Incidence	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)
Secondary	Neonatal outcome: neonatal morbidity	Incidence	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)
Secondary	Neonatal outcome: birth weight		After the neonate is born