PRIORI: Synbiotics in Patients at RIsk fOr Preterm Birth

• Sponsor: Ziekenhuis Oost-Limburg (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05966649
• Collaborator: (none)
• Enrollment: 402
• Locations: 6
• Arms: 2
• Anticipated Duration (Months): 50.5
• Patients Per Site: 67
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Preterm Spontaneous Labor With Preterm Delivery; Preterm Birth; Microbial Colonization	Other: Synbiotics; Other: Placebo	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 402 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Synbiotics in Patients at RIsk fOr Preterm Birth: a Multi-center Double-blind Randomized Placebo-controlled trIal
• Actual Study Start Date: Mar 16, 2023
• Anticipated Primary Completion Date: Dec 1, 2026
• Anticipated Study Completion Date: Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Synbiotics Oral synbiotic (food supplement) containing 8 probiotic Lactobacillus strains, the prebiotics inulin, fructooligosaccharides (FOS) and D-mannose.	Other: Synbiotics; Oral synbiotic (food supplement) containing 8 probiotic Lactobacillus strains, the prebiotics inulin, fructooligosaccharides (FOS) and D-mannose.
Placebo Comparator: Placebo Matching placebo	Other: Placebo; Matching placebo

Outcome Measures

Primary Outcome Measures

1. Gestational age at delivery [Through study completion - at delivery]

Secondary Outcome Measures

1. Incidence of PTB, defined as GA at delivery < 37 weeks [Through study completion - at delivery]

2. 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

3. PPROM [Up to 34 weeks from the date of randomization]

   Incidence

4. PPROM [Up to 34 weeks from the date of randomization]

   Gestational age at PPROM

5. PPROM [Up to 34 weeks from the date of randomization]

   Time to delivery

6. 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.

7. 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)]

8. 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)]

9. Incidence of maternal admissions [Up to 34 weeks from the date of randomization]

10. Duration of maternal admissions [Up to 34 weeks from the date of randomization]

11. Quality Of Life during pregnancy and during neonatal admission at a neonatal intensive care unit [Trough study completion, on avarage 1 year]

    Using EQ5D questionnaire (5 questions and scale from 1 to 100)

12. 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

13. 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)

14. 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

15. 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

16. 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

17. 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

18. 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

19. Neonatal outcome: birth weight [After the neonate is born]

Other Outcome Measures

1. Effect of antibiotics on the vaginal microbiome [During pregnancy until 28 days after PPROM]

   When the patient is admitted in case the pregnancy was complicated with PPROM

2. Effect on the gastrointestinal microbiome of the neonate in case of PPROM [Between 13 to 36 weeks from the date of randomization]

   When the neonate is born after a pregnancy complicated with PPROM

3. Placental microbiome in case of preterm birth [Between 13 to 36 weeks from the date of randomization]

   In case the pregnancy was complicated with preterm birth (delivery before 37 weeks of gestation)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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 37 weeks following PPROM, preterm labor or cervical insufficiency

• PPROM ≤37 weeks in previous pregnancy but delivery ≥37 weeks

• 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

2. Multiple pregnancy

3. Need for primary (type 1) cerclage

4. Inflammatory bowel disease

5. Known congenital uterine anomaly

6. History of LLETZ conization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ziekenhuis Oost-Limburg	Genk	Limburg	Belgium	3600
2	Universitaire Ziekenhuizen Leuven	Leuven	Limburg	Belgium	3000
3	UZ Gent	Gent	Oost-Vlaanderen	Belgium	9000
4	AZ Sint-Jan	Brugge	West-Vlaanderen	Belgium	8300
5	AZ Sint-Lucas	Brugge	West-Vlaanderen	Belgium	8310
6	CHR Citadelle	Liège		Belgium	4000

Sponsors and Collaborators

• Ziekenhuis Oost-Limburg

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ziekenhuis Oost-Limburg
• ClinicalTrials.gov Identifier: NCT05966649
• Other Study ID Numbers: Z-2022080
• First Posted: Jul 28, 2023
• Last Update Posted: Jul 28, 2023
• Last Verified: Jun 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ziekenhuis Oost-Limburg: Preterm birth; Vaginal microbiome; Probiotics; Synbiotics
• Additional relevant MeSH terms: Communicable Diseases; Infections; Premature Birth

Study Results

No Results Posted as of Jul 28, 2023