Clinical trial NCT04172012: Use of Probiotics to Reduce Infections, Death and ESBL Colonisation
Official title: Use of Probiotics to Reduce Infections and Death and Prevent Colonization With Extended-spectrum Beta-lactamase Producing Bacteria, Among Newborn Infants in Haydom and Surrounding Area, Tanzania, a Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neonatal Sepsis
Keywords: Tanzania
East Africa
Antimicrobial resistance
Probiotics
Extended Spectrum Beta-Lactamase Producing Bacteria
Lead sponsor: Haydom Lutheran Hospital
Sponsor class: OTHER
Collaborators: name: University of Bergen
name: Helse Stavanger HF
name: UiT The Arctic University of Norway
name: Muhimbili University of Health and Allied Sciences
First posted: 2019-11-21
Enrollment: 2000
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-controlled double-blinded randomized clinical trial
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite outcome hospitalization and death
timeFrame: 6 months from inclusion
Secondary outcomes:
measure: ESBL colonization
timeFrame: 6 weeks and 6 months
measure: Hospitalisation
timeFrame: 6 weeks and 6 months
measure: Death
timeFrame: 6 months
measure: Body weight
timeFrame: 6 months
measure: Body length
timeFrame: 6 months
measure: Stool microbiota
timeFrame: 6 weeks and 6 months
measure: Stool metabolome
timeFrame: 6 weeks and 6 months
measure: Stool inflammatory markers - Calprotectin
timeFrame: 6 weeks and 6 months
measure: Stool inflammatory markers - alpha-1 antitrypsin
timeFrame: 6 weeks and 6 months
measure: Stool inflammatory markers - myeloperoxidase
timeFrame: 6 weeks and 6 months
measure: Number of participants with culture-confirmed bacteremia
timeFrame: 6 months
measure: Genetic characteristics of ESBL-producing Enterobacteriaceae
timeFrame: 6 weeks and 6 months
Other outcomes:
Locations:
city: Babati
country: Tanzania
facility: Haydom Lutheran Hospital
state: Manyara
Study officials:
affiliation: University of Bergen
name: Nina Langeland, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.