Clinical trial NCT05500482: Vellore Typhoid Vaccine Impact Trial
Official title: Vellore Typhoid Vaccine Impact Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Typhoid Fever
Keywords: typhoid conjugate vaccine
cluster randomised trial
Enteric Fever
Lead sponsor: Christian Medical College, Vellore, India
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: University College, London
name: Imperial College London
First posted: 2022-08-15
Enrollment: 72500
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This cluster randomised trial will examine the impact of introducing TyphiBEV, a typhoid conjugate vaccine licensed in India, on the incidence of typhoid fever in a high burden urban setting in South India.

Detailed description: TyphiBEV®, a typhoid conjugate vaccine from Biological E, has been licensed by the Central Drugs Standard Control Organaisation in India based on immunogenicity and safety data. A similar typhoid conjugate vaccine has been demonstrated in large clinical trials to provide 80% vaccine efficacy in Nepal and Bangladesh. The TyphiBEV® has not been similarly evaluated. The demonstration of the impact of a city-scale typhoid conjugate vaccine introduction on the burden of typhoid will aid policy decisions on the use of typhoid conjugate vaccines in the national immunisation program.

After written informed consent, the investigators will establish stimulated passive surveillance in 72,000 individuals between 1 and 30 years of age within the Vellore Demographic Surveillance System to determine the incidence of blood-culture confirmed typhoid fever. Thirty-six thousand surveillance participants between 1 year and 30 years residing in the 30 clusters (areas) randomised to receive the vaccine will receive the vaccine at the beginning of the trial. Those in other areas will receive the same at the end of two years. Using a stimulated passive surveillance approach, those with acute febrile illness will be encouraged to visit study surveillance hospitals. Participants will be evaluated for blood-culture confirmed typhoid fever if they are eligible. The incidence of typhoid among those living in areas assigned to vaccination compared to those whose residence is in areas not designated for vaccination will be used to calculate the impact of the vaccine on disease burden.

Eligibility criteria: Inclusion Criteria:

* Consent

  * For adults, 18 years and over - they must be willing and competent to provide informed consent
  * For those aged under 18 years, the parent/guardian is willing and competent to provide informed consent, and if the participant is 11 to 18 years of age, informed assent will also be sought,
* Age:

  * Between 1 and 30 years (i.e., up to 29 years 364 days) at time of recruitment into the surveillance
  * Currently living within the study catchment area with no plans to leave the study area in the next 24 months

Exclusion Criteria:

* For fever surveillance

  o Medical reasons that prevent the participant from complying with study requirements including follow up and testing during illness
* For vaccination

  * Has received a typhoid vaccine in the previous three years
  * Is known to have an allergy to any vaccine component
  * Nursing mothers, Pregnancy or planning pregnancy around vaccination
  * Receipt of any other vaccine in the past 30 days (temporary exclusion)
  * Febrile illness in the 24 hours before vaccination (temporary exclusion)

Primary outcomes:
measure: Total effect
timeFrame: at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters.
Secondary outcomes:
measure: Overall effect
timeFrame: at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters.
measure: Effect in children 1 to 14 years
timeFrame: at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters.
measure: Effect on all febrile illness requiring healthcare visits
timeFrame: at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters.
measure: Safety outcomes
timeFrame: Seven days after vaccine receipt
Other outcomes:
measure: Indirect effect
timeFrame: at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters.
measure: Effect on hospitalised typhoid fever
timeFrame: at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters.
Locations:
city: Vellore
country: India
facility: Christian Medical College Vellore
state: Tamil Nadu
Study officials:
affiliation: Christian Medical College, Vellore, India
name: Jacob John, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Christian Medical College, Vellore, India
name: Gagandeep Kang, MD PhD
role: STUDY_CHAIR
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