ROTA-biotic: Measuring the Impact of Rotavirus Vaccines on Paediatric Antibiotic Usage

NCT06882070 | Completed DMC

• 1 other identifier: 219775/Z/19/Z
• Study Type: observational
• Target: 1,600
• Locations: 2 countries
• Sites: 2

Brief Summary

Rotavirus is the most common aetiology of serious diarrhoea in young children. Despite antibiotics not being indicated in its treatment, diarrhoea remains a very common cause for antibiotic prescribing in low-income settings. We hypothesized that effective rotavirus vaccination could reduce diarrhoeal episodes and thereby unnecessary antibiotic usage in young children in low-income settings. The study aimed to evaluate the impact of rotavirus vaccination on antibiotic usage. Specifically, the study quantified how differences in rotavirus vaccine efficacy would impact days of prescription and nonprescription antibiotic usage in the first 2 years of life among two large cohorts of children in Zambia and Ghana. The key goal was to understand the effect of rotavirus vaccine efficacy on antibiotic usage and household antibiotic costs. The goal was to generate evidence needed to inform policymakers seeking to introduce new rotavirus vaccines into national vaccination programs, of potential, and often under-appreciated, secondary effects of rotavirus vaccine implementation on antibiotic usage. The study was conducted within a Phase III randomised controlled trial comparing the efficacy of a new parenteral trivalent P2-VP8 subunit rotavirus vaccine to the oral live attenuated vaccine, Rotarix®, against severe rotavirus gastroenteritis in the first 2 years of life in Zambia and Ghana.

Conditions

Rotavirus Gastroenteritis; Rotavirus Vaccines; Antimicrobial Resistance (AMR); Antibiotic; Microbiome; Infant Diarrhea

Outcome Measures

Primary Outcomes (1)

• To assess the relative efficacy of the TV P2-VP8 vaccine in comparison to Rotarix® in reducing prescription and non-prescription antibiotic consumption in the first two years of life.

  2 years

Secondary Outcomes (6)

• • To assess the relative efficacy of the TV P2-VP8 vaccine in comparison to Rotarix® in reducing recurrent antibiotic consumption in the first two years of life.

  2 years

• • To assess the relative efficacy of the TV P2-VP8 vaccine in comparison to Rotarix® in reducing household prescription and non-prescription antibiotic costs in the first two years of life.

  2 years

• • To assess the background incidence of antibiotic usage in the community in the first two years of life.

  2 years

• • To assess the relationship between frequency of antibiotic use and faecal bacterial microbiome composition, ARG abundance and bacterial metabolites in the urine over the first two years of life.

  2 years

• • To assess the relationship between RVV efficacy (TV P2-VP8 and Rotarix) and faecal bacterial microbiome composition over the first two years of life.

  2 years

Study Arms (2)

Trial cohort

This group received either the trivalent P2-VP8 subunit rotavirus vaccine or oral live attenuated vaccine, Rotarix®,

Other: Vaccine

Community cohort

This acted as control group, away from the vaccine trial groups

Interventions

Vaccine OTHER

Trivalent P2-VP8 subunit rotavirus vaccine

Also known as: trivalent P2-VP8 subunit rotavirus vaccine, oral live attenuated vaccine, Rotarix®

Trial cohort

Eligibility Criteria

• Age: 6 Weeks - 8 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

The infants were from communities that are typical peri-urban settlements in Zambia and Ghana with informal housing, poor sanitation and mostly shared water supply from communal boreholes. These were high density communities with high unemployment rates and generally high incidence of infectious diseases.

You may qualify if:

• Healthy infants as established by medical history and clinical examination before randomisation into the study Age: ≥6 and \<8 weeks at the time of first study vaccination (42 days through 55 days old, inclusive, with the day after birth considered 1-day old) Parental ability and willingness to provide written informed consent. Intention of the participants' parents to remain in the area with the child during the study period

You may not qualify if:

• Presence of severe malnutrition (weight-for-height z-score ≤-3SD median (per WHO published child growth standards) History of premature birth (\<37 weeks gestation) and/or birth weight of \<2.5 kg History of congenital abdominal disorders, intussusception, or abdominal surgery Prior receipt of rotavirus vaccine

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Wellcome Trust: collaborator
• Centre for Infectious Disease Research in Zambia: collaborator
• Noguchi Memorial Institute for Medical Research: collaborator
• Amsterdam Institute for Global Health and Development: collaborator

Study Sites (2)

Noguchi Memorial Institute of Medical Research-University of Ghana

Accra, Ghana

Location

Center for Infectious Disease Research in Zambia

Lusaka, Lusaka Province, 10101, Zambia

Location

Biospecimen

Retention: SAMPLES WITH DNA

Stool and urine samples

MeSH Terms

Conditions

Diarrhea, Infantile

Interventions

Vaccines; Vaccines, Attenuated; RIX4414 vaccine

Condition Hierarchy (Ancestors)

Diarrhea; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: March 12, 2025
• First Posted: March 18, 2025
• Study Start: May 4, 2021
• Primary Completion: June 4, 2024
• Study Completion: June 4, 2024
• Last Updated: March 18, 2025

Record last verified: 2024-12

Locations

GH (1); ZA (1)