Neonatal Sepsis
Conditions
Keywords
Tanzania, East Africa, Antimicrobial resistance, Probiotics, Extended Spectrum Beta-Lactamase Producing Bacteria
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.
Interventions
BIOLOGICALLabinic (R) probiotic mixture
Labinic (R) probiotic mixture containing Lactobacillus acidophilus and Bifidobacterium infantis and B. breve
OTHERPlacebo
Placebo mixture
Sponsors
University of Bergen
Helse Stavanger HF
UiT The Arctic University of Norway
Muhimbili University of Health and Allied Sciences
Haydom Lutheran Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Investigational product (probiotic) and placebo product have both been produced by the same manufacturer and is delivered in identical bottles.
Intervention model description
Placebo-controlled double-blinded randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
No minimum to 3 Days
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
* Birth weight below 2 kg * Other health problems/illness, obvious congenital malformations. * Multiple pregnancy * Parents not consenting
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite outcome hospitalization and death | 6 months from inclusion | Primary outcome is hospitalization and/or death of study subject |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalisation | 6 weeks and 6 months | Hospitalisation |
| Death | 6 months | Death during study period |
| 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) |
| ESBL colonization | 6 weeks and 6 months | Faecal colonisation with Extended-spectrum beta-lactamase-producing Enterobacteriaceae as detected by fecal swab |
| 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 |
| Stool inflammatory markers - myeloperoxidase | 6 weeks and 6 months | Levels of human myeloperoxidase (MPO) in participants' stool samples |
| Number of participants with culture-confirmed bacteremia | 6 months | Bacteremia confirmed by blood culture |
| Genetic characteristics of ESBL-producing Enterobacteriaceae | 6 weeks and 6 months | Genetic characteristics of ESBL-E from colonization and clinical samples (targeted screening) |
| Stool metabolome | 6 weeks and 6 months | Stool metabolome composition |
Countries
Tanzania
Outcome results
None listed