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CompletedNCT04172012ProRIDEUpdated Apr 25, 2025

Use of Probiotics to Reduce Infections, Death and ESBL Colonisation

A Phase 3 interventional study of Labinic (R) probiotic mixture and Placebo in Neonatal Sepsis, sponsored by Haydom Lutheran Hospital. Completed at 1 site in Tanzania. Open to participants aged Up to 3 Days, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-04-25.

Sponsored by Haydom Lutheran Hospital · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
2,000
Allocation
Randomized
Ages
Up to 3 Days
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Neonatal Sepsis

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Keywords

  • Tanzania
  • East Africa
  • Antimicrobial resistance
  • Probiotics
  • Extended Spectrum Beta-Lactamase Producing Bacteria
03

Who can participate

Ages eligible
Up to 3 Days
Sexes eligible
All
Accepts healthy volunteers
Yes

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

Exclusion Criteria:

  • Birth weight below 2 kg
  • Other health problems/illness, obvious congenital malformations.
  • Multiple pregnancy
  • Parents not consenting
04

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
2,000 participants (actual)

Study arms

  • Active comparator
    Probiotic

    Study subjects receive probiotic mixture for 4 weeks

    Biological: Labinic (R) probiotic mixture

  • Placebo comparator
    Placebo

    Study subjects receive placebo mixture for 4 weeks

    Other: Placebo

Interventions

  • BiologicalLabinic (R) probiotic mixture

    Labinic (R) probiotic mixture containing Lactobacillus acidophilus and Bifidobacterium infantis and B. breve

  • OtherPlacebo

    Placebo mixture

05

What researchers measure

Primary outcomes

  1. Composite outcome hospitalization and death

    Primary outcome is hospitalization and/or death of study subject

    Time frame: 6 months from inclusion

Secondary outcomes

  1. ESBL colonization

    Faecal colonisation with Extended-spectrum beta-lactamase-producing Enterobacteriaceae as detected by fecal swab

    Time frame: 6 weeks and 6 months

  2. Hospitalisation

    Hospitalisation

    Time frame: 6 weeks and 6 months

  3. Death

    Death during study period

    Time frame: 6 months

  4. Body weight

    Growth monitored by weight

    Time frame: 6 months

  5. Body length

    Growth monitored by length

    Time frame: 6 months

  6. Stool microbiota

    Stool microbiota composition including resistome analysis (metagenome sequencing)

    Time frame: 6 weeks and 6 months

  7. Stool metabolome

    Stool metabolome composition

    Time frame: 6 weeks and 6 months

  8. Stool inflammatory markers - Calprotectin

    Levels of Calprotectin in participants' stool samples

    Time frame: 6 weeks and 6 months

  9. Stool inflammatory markers - alpha-1 antitrypsin

    Levels of alpha-1 antitrypsin (AAT) in participants' stool samples

    Time frame: 6 weeks and 6 months

  10. Stool inflammatory markers - myeloperoxidase

    Levels of human myeloperoxidase (MPO) in participants' stool samples

    Time frame: 6 weeks and 6 months

  11. Number of participants with culture-confirmed bacteremia

    Bacteremia confirmed by blood culture

    Time frame: 6 months

  12. Genetic characteristics of ESBL-producing Enterobacteriaceae

    Genetic characteristics of ESBL-E from colonization and clinical samples (targeted screening)

    Time frame: 6 weeks and 6 months

06

Study locations

1 site
  • Haydom Lutheran Hospital
    Babati, Manyara, Tanzania
07

References and documents

Publications

  • Panigrahi P, Parida S, Nanda NC, Satpathy R, Pradhan L, Chandel DS, Baccaglini L, Mohapatra A, Mohapatra SS, Misra PR, Chaudhry R, Chen HH, Johnson JA, Morris JG, Paneth N, Gewolb IH. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature. 2017 Aug 24;548(7668):407-412. doi: 10.1038/nature23480. Epub 2017 Aug 16. PubMed 28813414 ↗
  • Esaiassen E, Hjerde E, Cavanagh JP, Pedersen T, Andresen JH, Rettedal SI, Stoen R, Nakstad B, Willassen NP, Klingenberg C. Effects of Probiotic Supplementation on the Gut Microbiota and Antibiotic Resistome Development in Preterm Infants. Front Pediatr. 2018 Nov 16;6:347. doi: 10.3389/fped.2018.00347. eCollection 2018. PubMed 30505830 ↗
  • Tellevik MG, Blomberg B, Kommedal O, Maselle SY, Langeland N, Moyo SJ. High Prevalence of Faecal Carriage of ESBL-Producing Enterobacteriaceae among Children in Dar es Salaam, Tanzania. PLoS One. 2016 Dec 9;11(12):e0168024. doi: 10.1371/journal.pone.0168024. eCollection 2016. PubMed 27936054 ↗
  • Kuwelker K, Langeland N, Lohr IH, Gidion J, Manyahi J, Moyo SJ, Blomberg B, Klingenberg C. Use of probiotics to reduce infections and death and prevent colonization with extended-spectrum beta-lactamase (ESBL)-producing bacteria among newborn infants in Tanzania (ProRIDE Trial): study protocol for a randomized controlled clinical trial. Trials. 2021 Apr 29;22(1):312. doi: 10.1186/s13063-021-05251-3. PubMed 33926519 ↗

Study documents

  • Study protocol · Dec 19, 2021
  • Statistical analysis plan · May 8, 2023
  • Informed consent form · Dec 19, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT04172012
Lead sponsor
Haydom Lutheran Hospital
Collaborators
University of Bergen, Helse Stavanger HF, UiT The Arctic University of Norway, Muhimbili University of Health and Allied Sciences
Responsible party
Sponsor
First posted
Nov 21, 2019
Start date
Feb 1, 2022
Primary completion
Jul 10, 2023
Completion
Sep 19, 2023
Last update
Apr 25, 2025

Study contacts

Nina Langeland, MD, PhD
principal investigator · University of Bergen

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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