TyVAC Nepal: typhoid vaccine study
| ISRCTN | ISRCTN43385161 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN43385161 |
| Secondary identifying numbers | OVG2017/05 |
- Submission date
- 20/06/2017
- Registration date
- 26/09/2017
- Last edited
- 11/10/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Current plain English summary as of 13/08/2018:
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), grant number OPP1151153
Who is the main contact?
Prof. Andrew Pollard
Previous 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
Contact information
Scientific
Oxford Vaccine Group
Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)
Churchill Hospital Old Road
Oxford
OX3 7LE
United Kingdom
 ORCID ID |
0000-0001-7361-719X |
|---|
Study information
| Study design | Participant- and observer-blind randomised-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Community |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Assessing the impact of a Vi-Polysaccharide Conjugate Vaccine in preventing typhoid infection among Nepalese children – a Phase III trial |
| Study objectives | 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(s) | 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 |
| Health condition(s) or problem(s) studied | Blood culture confirmed typhoid fever |
| Intervention | Current interventions as of 13/08/2018: 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, and all children who received the intervention vaccine will also be offered the control meningococcal group A vaccine. 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. Previous interventions: 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | TyBar (Vi-TCV), MenAfriVac |
| Primary outcome measure | 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 Added 20/06/2019: 7. 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 with at least 3 days of fever, for the duration of the trial in each vaccination arm |
| Overall study start date | 01/11/2017 |
| Completion date | 01/08/2020 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Child |
| Lower age limit | 9 Months |
| Upper age limit | 16 Years |
| Sex | Both |
| Target number of participants | 20,000 |
| Total final enrolment | 20019 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/11/2017 |
| Date of final enrolment | 09/04/2018 |
Locations
Countries of recruitment
- Nepal
Study participating centre
-
Nepal
Sponsor information
University/education
University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom
"ROR" |
https://ror.org/052gg0110 |
|---|
Funders
Funder type
Charity
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Bill & Melinda Gates Foundation, Gates Foundation, BMGF, B&MGF, GF
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/08/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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. Added 20/06/2019: An interim analysis will be conducted after 45 cases have been identified and one year of follow-up has been reached. The results of the interim analysis will be published in a high impact journal. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Andrew Pollard. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 07/03/2019 | 08/03/2019 | Yes | No |
| Results article | results | 05/12/2019 | 06/12/2019 | Yes | No |
| Results article | 09/11/2021 | 26/10/2021 | Yes | No | |
| Results article | Under-detection of blood culture-positive enteric fever cases: The impact of missing data and methods for adjusting incidence estimates | 16/01/2020 | 11/10/2023 | Yes | No |
Editorial Notes
11/10/2023: Publication reference added.
26/10/2021: Publication reference added.
06/12/2019: Publication reference and total final enrolment number added.
20/06/2019: The secondary outcome measures and publication and dissemination plan were updated.
08/03/2019: Publication reference added.
01/03/2019: Internal review.
13/08/2018: The following changes have been made to the trial record:
1. The interventions were updated
2. The recruitment end date was changed from 01/03/2018 to 09/04/2018
3. The plain English summary has been updated
