Vellore Typhoid Vaccine Impact Trial (VEVACT)

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.

Study Overview

• Status: Recruiting
• Conditions: Typhoid Fever
• Intervention / Treatment: Biological: Typhoid conjugate Vaccine

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.

• Study Type: Interventional
• Enrollment (Estimated): 72500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jacob John, MD PhD; Phone Number: 00919442631628; Email: jebu@cmcvellore.ac.in

Study Locations

• India
  • Tamil Nadu
    • Vellore, Tamil Nadu, India, 632002
      • Recruiting
      • Christian Medical College Vellore
      • Contact: Jacob John, MD PhD; Phone Number: 00914162284401; Email: vevact@tyimpact.in
      • Sub-Investigator: Gagandeep Kang, MD PhD
      • Sub-Investigator: Winsley Rose, MD
      • Sub-Investigator: Venkataraghava Mohan, MD
      • Sub-Investigator: Prasanna Samuel, PhD
      • Sub-Investigator: Priscilla Rupali, MD
      • Sub-Investigator: Vinod J Abraham, MD
      • Sub-Investigator: Nicholas C Grassly, DPhil
      • Sub-Investigator: Tim Morris, PhD
      • Sub-Investigator: Andrew Copas, PhD
      • Sub-Investigator: Jason Andrews, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 30 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccinated arm; Typhoid Conjugate Vaccine (TyphiBEV) 0.5 ml as a single dose given intramuscularly to consenting, eligible residents of vaccine clusters	Biological: Typhoid conjugate Vaccine; TyphiBEV is a clear colourless monovalent vaccine containing 25 µg of Typhoid Vi polysaccharide manufactured using the Citrobacter freundii sensu lato3056 (Vi) and is conjugated to CRM 197 as a carrier protein. Sodium chloride and Phosphate buffer are used as a buffering agent in the vaccine formulation with 2-Phenoxyethanol as a preservative.; Other Names: TyphiBEV
No Intervention: Control arm; No vaccination in the control clusters

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total effect	Number of blood culture confirmed typhoid fever episodes in vaccinated participants from vaccine clusters compared to the number of blood culture confirmed typhoid fever episodes in unvaccinated participants from non-vaccine clusters	at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety outcomes	The number and description of solicited and non-solicited adverse events reported within the first seven days after vaccination in the safety subset of vaccine recipients	Seven days after vaccine receipt
Overall effect	The number of blood culture confirmed typhoid fever episodes in participants from vaccine clusters compared to the number of blood culture confirmed typhoid fever episodes in participants from non-vaccine clusters	at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters.
Effect in children 1 to 14 years	The number of blood culture confirmed typhoid fever episodes in vaccinated children between 1 year and 14 years and 364 days from vaccine clusters compared to the number of blood culture confirmed typhoid fever episodes in unvaccinated children between 1 year and 14 years and 364 days from non-vaccine clusters	at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters.
Effect on all febrile illness requiring healthcare visits	The number of febrile illness episodes where healthcare is sought among vaccinated participants from vaccine clusters compared to unvaccinated participants from non-vaccine clusters	at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indirect effect	The number of blood culture confirmed typhoid fever episodes in unvaccinated participants from vaccine clusters compared to the number of blood culture confirmed typhoid fever episodes in unvaccinated participants from non-vaccine clusters	at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters.
Effect on hospitalised typhoid fever	The number of blood culture confirmed typhoid fever episodes in hospitalised participants who have been vaccinated compared to the number of blood culture confirmed typhoid fever episodes in hospitalised participants who have not been vaccinated	at 24 months of follow up beginning 28 days after vaccine introduction in vaccine clusters.

Collaborators and Investigators

• Sponsor: Christian Medical College, Vellore, India
• Collaborators: Imperial College London; University College, London; Bill and Melinda Gates Foundation
• Investigators: Principal Investigator: Jacob John, MD PhD, Christian Medical College, Vellore, India; Study Chair: Gagandeep Kang, MD PhD, Christian Medical College, Vellore, India

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: August 8, 2022
• First Posted (Actual): August 15, 2022

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: cluster randomised trial; typhoid conjugate vaccine; Enteric Fever
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Salmonella Infections; Typhoid Fever
• Other Study ID Numbers: 14247[INTERVEN]

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All de-identified individual level data as permitted by the local law will be made available on Mendeley Data. Access to data will be possible by writing to the vevact@tympact.in on or after 31 Dec 2025
• IPD Sharing Time Frame: Within 6 months of data lock at the end of the trial and for a period of five years thereafter
• IPD Sharing Access Criteria: Upon providing a draft hypothesis and analysis plan
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No