Condition category
Infections and Infestations
Date applied
20/06/2017
Date assigned
26/09/2017
Last edited
26/09/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Typhoid fever is a bacterial infection that can cause severe disease and even death. Typhoid is spread through contaminated food and water, due to poor hygiene and sanitation conditions. In Nepal, typhoid fever causes a lot of disease, mostly in children. Previous vaccines have not provided long-term protection for children. A new typhoid vaccine, Vi-TCV, has been developed and is licensed for use in Nepal. This vaccine is safe for children and may provide long-term protection. However, this vaccine is not yet available through the routine childhood immunisation programme. Before the government will introduce the vaccine into the routine programme, more information is needed on the level of protection that the vaccine provides. The aim of this study is to find out whether the typhoid vaccine Vi-TCV reduces the incidence of typhoid fever in children.

Who can participate?
Children under the age of 16

What does the study involve?
Participants are randomly allocated to either receive the typhoid vaccine (Vi-TCV) or a vaccine which protects against meningitis. Participants are followed-up over a two-year period. When participants develop a fever during that time, they are asked to come to the local hospital or the study clinics in the community. If they have a fever over 38 degrees C or if they have had a fever for 2 or more days they receive treatment and a blood test to check if they have typhoid fever. The cost of treatment for suspected or confirmed typhoid is covered by the study. All participants are also monitored for side effects associated with the vaccine. At the end of the study, all of the children who first received the meningitis vaccine are offered the typhoid vaccine too.

What are the possible benefits and risks of participating?
Participants benefit from the study by receiving the typhoid vaccine for free, which is not currently available through the routine immunisation system in Nepal. Participants also have free treatment for any suspected or confirmed typhoid infections. The vaccine has been found to be safe in all previous studies, but since this is the largest study of this vaccine to date, there is a risk for participants that a rare side effect, not yet identified, may become apparent in this study.

Where is the study run from?
Patan Hospital (Nepal)

When is the study starting and how long is it expected to run for?
November 2017 to August 2020

Who is funding the study?
Bill and Melinda Gates Foundation (USA)

Who is the main contact?
Prof. Andrew Pollard

Trial website

Contact information

Type

Scientific

Primary contact

Prof Andrew Pollard

ORCID ID

http://orcid.org/0000-0001-7361-719X

Contact details

Oxford Vaccine Group
Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)
Churchill Hospital Old Road
Oxford
OX3 7LE
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

OVG2017/05

Study information

Scientific title

Assessing the impact of a Vi-Polysaccharide Conjugate Vaccine in preventing typhoid infection among Nepalese children – a Phase III trial

Acronym

Study hypothesis

The typhoid vaccine, Vi-TCV, will reduce the incidence of laboratory confirmed typhoid fever in children receiving the vaccine, compared to those receiving a control vaccine.

Ethics approval

1. Nepal Health Research Council (NHRC), 16/08/2017, reference number: 386, registration number: 170/2017
2. Oxford Tropical Research Ethics Council (OxTREC), 10/08/2017, ref: 15-17

Study design

Participant- and observer-blind randomised-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Community

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Blood culture confirmed typhoid fever

Intervention

Participants will be randomised (block randomisation) 1:1 to receive a single dose of either Vi-TCV or MenA vaccine:
Intervention: Vi Typhoid conjugate vaccine (Vi-TCV), trade name: TyBar
Control: Meningococcal group A vaccine (MenA), trade name: MenAfriVac
Neither the participants or the researchers will know which vaccine any child has received until the end of trial. At the end of the trial, once it is unblinded, and everyone knows which vaccine they received, all of the children who first received the control vaccine will be offered the typhoid vaccine too.

Participants will be followed-up over a two year period. When participants develop a fever during that time, they will be asked to come to the local hospital or the trial clinics in the community. If they have a fever over 38 degrees C, or if they have had a fever for 2 or more days, they will get treatment and a blood test to check if they have typhoid fever. The cost of treatment for suspected or confirmed typhoid will be covered by the trial. All participants will also be monitored for safety outcomes associated with the vaccine.

Intervention type

Biological/Vaccine

Phase

Drug names

Primary outcome measures

The efficacy and rate reduction of the Vi-TCV in preventing blood culture-confirmed symptomatic infection caused by S. Typhi, measured through the incidence of blood culture confirmed typhoid fever in participants presenting to hospital or clinic for the duration of the trial, in each vaccination arm

Secondary outcome measures

1. Vi-TCV vaccine safety, measured as the proportion of participants developing all adverse events within the first 7 days post-vaccination, and serious adverse events within 6 months of vaccination, as determined through self-reporting at three-monthly follow-up contact
2. The impact of vaccination with Vi-TCV on the incidence of inpatient/outpatient admission rates for fever, measured by the rates of participants with at least ≥2 days of subjective persistent fever, or a temperature of at least 38 degrees C, at presentation at Patan Hospital or trial clinics in each vaccination arm, stratified by duration and severity of fever
3. The difference in rates of hospital and clinic presentation for febrile illness in each vaccination arm, measured as the rates of hospital or clinic presentation with febrile illness of any duration in each vaccination arm, measured by hospital presentation logs, hospital records, trial clinic records and self-reporting during three monthly follow-up
4. Days spent in hospital from febrile illness, measured as the length of stay in hospital, collected from Patan hospital patient records, and parent/self-reported, in each vaccination arm
5. Incidence of clinically-suspected enteric fever, measured as the number of clinical diagnoses of typhoid fever, as determined by trial staff in Patan hospital outpatient clinics and trial clinic, in each vaccination arm throughout the two year follow-up period
6. Paratyphoid infection rates in each vaccination arm, measured as the rates of blood culture confirmed Paratyphoid cases in participants presenting to hospital or clinic for the duration of the trial, in each vaccination arm

Overall trial start date

01/11/2017

Overall trial end date

01/08/2020

Reason abandoned

Eligibility

Participant inclusion criteria

1. Parent/legal guardian is willing and competent to provide informed consent. If the participant is 12 years of age or older, informed assent will also be sought
2. Aged between 9 months (or eligible for measles vaccination according to local protocol) and <16 years (i.e. up to 15 years 364 days) at time of vaccination
3. In good health on the day of vaccination
4. Parent/legal guardian confirms that their child will be wiling and be able to comply with study requirements including follow-up contact, according the trial schedule
5. Live within the study catchment area at the time of vaccination

Participant type

Healthy volunteer

Age group

Child

Gender

Both

Target number of participants

20,000

Participant exclusion criteria

The participant will not be enrolled if any of the following criteria apply:
1. They have knowingly received a typhoid vaccine in the last three years
2. They have a known allergy to any of the vaccine components
3. Any medical or social reasons that will prevent the participant from conforming to the study requirements as judged by a medical professional
4. They are planning to move away from the catchment area within the next 6 months

Participants will be temporarily excluded from being vaccinated if, at point of vaccination, any of the following apply:
1. Reported fever within 24 hours prior to vaccination
2. Use of anti-pyretics within 4 hours prior to vaccination
If these apply, the participant will be temporarily excluded for vaccination until 48 hours has passed. A re-assessment will be conducted to ensure these temporary exclusion criteria no longer exist

Recruitment start date

01/11/2017

Recruitment end date

01/03/2018

Locations

Countries of recruitment

Nepal

Trial participating centre

Patan Hospital
Kathmandu
-
Nepal

Sponsor information

Organisation

University of Oxford

Sponsor details

University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Bill and Melinda Gates Foundation

Alternative name(s)

Bill & Melinda Gates Foundation

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United States of America

Results and Publications

Publication and dissemination plan

It is planned that the results of this trial will be published in high-impact peer reviewed journals within one year of the conclusion of the trial, around August 2021.

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Andrew Pollard.

Intention to publish date

01/08/2021

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes