Use of Probiotics to Reduce Infections, Death and ESBL Colonisation

Neonatal Sepsis Clinical Trial

— ProRIDE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04172012
• Other study ID #: 2019/1025
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 1, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: December 2023
• Source: Haydom Lutheran Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2000
• Est. completion date: December 31, 2024
• Est. primary completion date: July 10, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 3 Days

Eligibility

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

Related Conditions & MeSH terms

• Neonatal Sepsis

Intervention

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

Other:
• Placebo
Placebo mixture

Locations

Country	Name	City	State
Tanzania	Haydom Lutheran Hospital	Babati	Manyara

Sponsors (5)

Lead Sponsor	Collaborator
Haydom Lutheran Hospital	Helse Stavanger HF, Muhimbili University of Health and Allied Sciences, UiT The Arctic University of Norway, University of Bergen

Country where clinical trial is conducted

Tanzania, 

References & Publications (3)

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. — View 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. Erratum In: Nature. 2017 Nov 29;: — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite outcome hospitalization and death	Primary outcome is hospitalization and/or death of study subject	6 months from inclusion
Secondary	ESBL colonization	Faecal colonisation with Extended-spectrum beta-lactamase-producing Enterobacteriaceae as detected by fecal swab	6 weeks and 6 months
Secondary	Hospitalisation	Hospitalisation	6 weeks and 6 months
Secondary	Death	Death during study period	6 months
Secondary	Body weight	Growth monitored by weight	6 months
Secondary	Body length	Growth monitored by length	6 months
Secondary	Stool microbiota	Stool microbiota composition including resistome analysis (metagenome sequencing)	6 weeks and 6 months
Secondary	Stool metabolome	Stool metabolome composition	6 weeks and 6 months
Secondary	Stool inflammatory markers - Calprotectin	Levels of Calprotectin in participants' stool samples	6 weeks and 6 months
Secondary	Stool inflammatory markers - alpha-1 antitrypsin	Levels of alpha-1 antitrypsin (AAT) in participants' stool samples	6 weeks and 6 months
Secondary	Stool inflammatory markers - myeloperoxidase	Levels of human myeloperoxidase (MPO) in participants' stool samples	6 weeks and 6 months
Secondary	Number of participants with culture-confirmed bacteremia	Bacteremia confirmed by blood culture	6 months
Secondary	Genetic characteristics of ESBL-producing Enterobacteriaceae	Genetic characteristics of ESBL-E from colonization and clinical samples (targeted screening)	6 weeks and 6 months