Clinical trial NCT06882070: ROTA-biotic: Measuring the Impact of Rotavirus Vaccines on Paediatric Antibiotic Usage
Official title: ROTA-biotic: Measuring the Impact of Rotavirus Vaccines on Paediatric Antibiotic Usage
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rotavirus Gastroenteritis
Rotavirus Vaccines
Antimicrobial Resistance (AMR)
Antibiotic
Microbiome
Infant Diarrhea
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Wellcome Trust
name: Centre for Infectious Disease Research in Zambia
name: Noguchi Memorial Institute for Medical Research
name: Amsterdam Institute for Global Health and Development
First posted: 2025-03-18
Enrollment: 1600
Sex: ALL
Minimum age (years): 6
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

Acute disease at the time of enrollment/first study vaccination - temporary exclusion Presence of fever on the day of enrollment/first study vaccination (axillary temperature \>37.6oC) Concurrent participation in another clinical trial (other than the parent study) throughout the entire timeframe for this study.

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

Primary outcomes:
measure: 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.
timeFrame: 2 years
Secondary outcomes:
measure: • 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.
timeFrame: 2 years
measure: • 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.
timeFrame: 2 years
measure: • To assess the background incidence of antibiotic usage in the community in the first two years of life.
timeFrame: 2 years
measure: • 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.
timeFrame: 2 years
measure: • To assess the relationship between RVV efficacy (TV P2-VP8 and Rotarix) and faecal bacterial microbiome composition over the first two years of life.
timeFrame: 2 years
measure: • Verification of weekly recall and medicine cabinet review of antibiotic use through assessment of antibiotic metabolites in the urine.
timeFrame: 2 years
Other outcomes:
Locations:
city: Accra
country: Ghana
facility: Noguchi Memorial Institute of Medical Research-University of Ghana
city: Lusaka
country: Zambia
facility: Center for Infectious Disease Research in Zambia
Study officials:
References: