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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Haydom Lutheran Hospital
- Enrollment
- 2,000
- Locations
- 1
- Primary Endpoint
- Composite outcome hospitalization and death
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, 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.
Eligibility Criteria
- Ages
- — to 3 Days (Child)
- Sex
- 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
- •Birth weight below 2 kg
- •Other health problems/illness, obvious congenital malformations.
- •Multiple pregnancy
- •Parents not consenting
Arms & Interventions
Placebo
Study subjects receive placebo mixture for 4 weeks
Intervention: Placebo (Other)
Probiotic
Study subjects receive probiotic mixture for 4 weeks
Intervention: Labinic (R) probiotic mixture (Biological)
Outcomes
Primary Outcomes
Composite outcome hospitalization and death
Time Frame: 6 months from inclusion
Primary outcome is hospitalization and/or death of study subject
Secondary Outcomes
- ESBL colonization(6 weeks and 6 months)
- Hospitalisation(6 weeks and 6 months)
- Death(6 months)
- Stool metabolome(6 weeks and 6 months)
- Body weight(6 months)
- Body length(6 months)
- Stool microbiota(6 weeks and 6 months)
- Stool inflammatory markers - Calprotectin(6 weeks and 6 months)
- Stool inflammatory markers - alpha-1 antitrypsin(6 weeks and 6 months)
- Number of participants with culture-confirmed bacteremia(6 months)
- Stool inflammatory markers - myeloperoxidase(6 weeks and 6 months)
- Genetic characteristics of ESBL-producing Enterobacteriaceae(6 weeks and 6 months)