Clinical trial NCT04852185: Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana
Official title: A Cluster-randomised Controlled Phase IV Trial Assessing the Impact of a Vi-Polysaccharide Conjugate Vaccine in Preventing Typhoid Infection in Asante Akim, Ghana (TyVEGHA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Typhoid Fever
Keywords: Typhoid
Typhoid conjugate vaccine
Cluster randomised trial
Lead sponsor: International Vaccine Institute
Sponsor class: OTHER
Collaborators: name: Kwame Nkrumah University of Science and Technology
name: University of Cambridge
name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Fondation Mérieux
name: University of Maryland, Baltimore
First posted: 2021-04-21
Enrollment: 23000
Sex: ALL
Minimum age (years): 9
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participant- and observer-blinded, cluster-randomised controlled Phase IV trial
Primary purpose: PREVENTION

Brief summary: A cluster-randomised controlled Phase IV trial (cRCT) assessing the impact of a Vi-Polysaccharide conjugate vaccine in preventing typhoid infection in Asante Akim, Ghana (TyVEGHA) with a primary endpoint of determining the total protection conferred by single-dose vaccination with Vi-TT against blood culture-confirmed symptomatic S. Typhi infection in the intervention vaccine clusters, compared with the control vaccine clusters.

Detailed description: Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates \>100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), the uptake of these vaccines in African countries has remained low. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, are critical to enhancing the introduction of TCVs in high-burden settings. Here we describe a cluster-randomized trial to investigate population-level protection of TCV against blood culture-confirmed typhoid fever. A total of 80 geographically distinct clusters have been delineated within the Agogo district of the Asante Akim region in Ghana. Clusters will be randomized to the intervention arm receiving TCV or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the overall protection of TCV against blood culture-confirmed typhoid fever. Total, direct, and indirect protection will be measured as secondary outcomes. Blood culture-based enhanced surveillance will enable the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs will improve uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings.

Eligibility criteria: Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet the following criteria:

* Healthy participants aged 9 months to \<16 years (i.e., ≤15 years and 364 days) of age at the time of vaccination
* Participants/Parents/legally authorized representative (LAR) who have voluntarily given informed assent (sought from participants aged 12 years to \<16 years) and informed consent
* Participants/Parents/LAR living within study target area at the time of vaccination and willing to follow the study procedures and be available for the entire duration of the study

Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study:

* Known allergy to any vaccine component
* Self-reported ongoing acute and/or chronic illness
* Any self-reported coagulopathies
* Any medical or social compelling reasons in the judgment of a clinical physician
* Self-reported pregnancy/Positive urine pregnancy test or lactating
* Previous typhoid vaccination in the last 5 years (proven by the presentation of a vaccine card or self-reporting).

Temporary exclusion criteria

* Self-reported fever (elevated tympanic (≥38°C) or axillary temperature (≥37.5°C)) within 24 hours of vaccination
* Self-reported use of antipyretics within 4hours prior to vaccination
* Any other vaccination during the last 4 weeks (proven by the presentation of a vaccine card or self-reporting)
* Girls ≥11 years of age with self-reported irregular menstruation or who do not know their last menstruation date

Primary outcomes:
measure: Total Protection
timeFrame: 3 years
Secondary outcomes:
measure: Safety Assessment
timeFrame: 3 years
measure: Overall protection
timeFrame: 3 years
measure: Total protection against severe typhoid.
timeFrame: 3 years
measure: Total protection against clinical typhoid.
timeFrame: 3 years
measure: Overall protection against clinical typhoid.
timeFrame: 3 years
measure: Indirect Protection aganist Blood Culture Confirmed Typhoid.
timeFrame: 3 years
measure: Seroconversion rates
timeFrame: 3 years
measure: Geometric mean titers
timeFrame: 3 years
Other outcomes:
Locations:
city: Kumasi
country: Ghana
facility: Kwame Nkrumah University of Science and Technology
state: Ashanti
Study officials:
affiliation: University of Cambridge
name: Florian Marks, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kwame Nkrumah University of Science and Technology
name: Ellis Owusu Dabo, PhD
role: PRINCIPAL_INVESTIGATOR
References: