Use of Probiotics to Reduce Infections, Death and ESBL Colonisation

Phase 3

Completed

• Conditions: Neonatal Sepsis
• Interventions: Other: Placebo; Biological: Labinic (R) probiotic mixture

• Registration Number: NCT04172012
• Lead Sponsor: Haydom Lutheran Hospital

Brief Summary

This study examines the effect of oral probiotic treatment to newborns on preventing hospitalizations, death and colonization with Extended-spectrum beta-lactamase-producing Gram negative bacteria. Half of the babies will receive 4 weeks treatment with an oral mixture of the probiotic Labinic (R) while the other half will receive a placebo mixture.

Detailed Description

Studies show that probiotics given to prematurely born babies prevents sepsis and is widely used in the western world for this purpose. Probiotics consists of one or more normal gut-bacteria. A large study in India showed that giving probiotics to full-born babies reduced hospitalizations and morbidity. This study investigates giving a probiotic mixture with different combination of bacteria, Lactobacillus acidophilus, Bifidobacterium infantis and Bifidobacterium breve, for a longer duration (4 weeks instead of 7 days).

Infections with antibiotic-resistant bacteria is a major threat to health-care world-wide, and sepsis/severe infection caused by such bacteria is a major cause of neonatal death. The study hypothesis is that giving probiotics to newborns prevents them from getting colonized with antibiotic-resistant bacteria, such as Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). By preventing colonization with ESBL-PE, severe infections such as sepsis may be prevented, and thereby survival may be improved.

Study Timeline

• Study First Submitted: 2019-11-19
• Study First Submitted QC: 2019-11-19
• Study First Posted: 2019-11-21
• Study Start: 2022-02-01
• Primary Completion: 2023-07-10
• Study Completion: 2023-09-19
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2000

Inclusion Criteria

• Healthy newborn infants with a birth weight equal or above 2.0 kgs, will be included in the study between 0-3 days of life.
• Newborn infants have to come from families who are long-term or permanent residents in the defined catchment area for this trial (30 km radius from HLH) in Tanzania.
• Parents are able and willing to complete study visit (including required study procedures) schedules over the six months proposed follow-up, which also includes hospitalizations required for compliance of this study protocol.
• Parents agrees for the child not to participate in another study during the study period
• Children less than one year admitted to hospital with suspected infection, not included in the RCT, will be included in a sub-study. A separate inclusion form is prepared for these children.

Exclusion Criteria

• Birth weight below 2 kg
• Other health problems/illness, obvious congenital malformations.
• Multiple pregnancy
• Parents not consenting

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Study subjects receive placebo mixture for 4 weeks
Probiotic	Labinic (R) probiotic mixture	Study subjects receive probiotic mixture for 4 weeks

Primary Outcome Measures

Name	Time	Method
Composite outcome hospitalization and death	6 months from inclusion	Primary outcome is hospitalization and/or death of study subject

Secondary Outcome Measures

Name	Time	Method
ESBL colonization	6 weeks and 6 months	Faecal colonisation with Extended-spectrum beta-lactamase-producing Enterobacteriaceae as detected by fecal swab
Hospitalisation	6 weeks and 6 months	Hospitalisation
Death	6 months	Death during study period
Stool metabolome	6 weeks and 6 months	Stool metabolome composition
Body weight	6 months	Growth monitored by weight
Body length	6 months	Growth monitored by length
Stool microbiota	6 weeks and 6 months	Stool microbiota composition including resistome analysis (metagenome sequencing)
Stool inflammatory markers - Calprotectin	6 weeks and 6 months	Levels of Calprotectin in participants' stool samples
Stool inflammatory markers - alpha-1 antitrypsin	6 weeks and 6 months	Levels of alpha-1 antitrypsin (AAT) in participants' stool samples
Number of participants with culture-confirmed bacteremia	6 months	Bacteremia confirmed by blood culture
Stool inflammatory markers - myeloperoxidase	6 weeks and 6 months	Levels of human myeloperoxidase (MPO) in participants' stool samples
Genetic characteristics of ESBL-producing Enterobacteriaceae	6 weeks and 6 months	Genetic characteristics of ESBL-E from colonization and clinical samples (targeted screening)

Trial Locations

Locations (1)

Haydom Lutheran Hospital; 🇹🇿 Babati, Manyara, Tanzania