Pneumococcal Vaccine Schedules (PVS)
| ISRCTN | ISRCTN15056916 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15056916 |
| Protocol serial number | SCC 1577 v1.2 |
| Sponsor | London School of Hygiene & Tropical Medicine |
| Funders | Medical Research Council, Wellcome Trust, Department for International Development, National Institute for Health Research, Bill and Melinda Gates Foundation |
- Submission date
- 19/09/2018
- Registration date
- 15/11/2018
- Last edited
- 05/12/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Pneumococcus bacteria are the most common cause of pneumonia (lung inflammation), septicemia (bacteria in the blood) and meningitis
(inflammation of the membranes around the brain) worldwide. Many countries have introduced pneumococcal conjugate vaccines (PCV) using three or four dose schedules and this has been followed by a drop in pneumococcal disease. Herd protection effects, in which vaccinatiuon of a proportion of the population reduces the spread of a disease within the unvaccinated population, have prevented more cases than the direct effects in vaccinated children. Many African and Asian countries have now introduced PCV using the standard schedule of three doses in early infancy (3+0 schedule).
Global control of pneumococcal disease however, is hampered by the cost of PCV. Low-income countries receive subsidised vaccine through the Gavi Alliance. However, when countries’ income per person exceeds the World Bank ‘low-income’ threshold, they ‘graduate’ from Gavi support and must pay a proportion of the cost. The cost of vaccine has prevented most middle-income countries from introducing PCV.
This study will test an alternative schedule that includes one early dose and a booster dose at 9 months of age, compared to the standard schedule. If this two-dose schedule is as effective as the three-dose schedule, this would make the cost of vaccinating lower. We aim to test if the impact of the alternative schedule is not worse than the standard schedule.
Who can participate?
Children aged 6 weeks to 365 days and living in the study area can receive the vaccine. The impact of the intervention will be measured in children aged 2 weeks to 59 months.
What does the study involve?
We plan to deliver two-dose (doses at age 6 weeks and 9 months, ‘1+1’) or three-dose (doses at age 6, 10, 14 weeks, ‘3+0’) schedules to infants resident in the study area over a period of 4 years. Vaccines will be administered at 68 immunisation clinics serving separate catchment populations. The immunisation clinic catchment population will be randomised to either group (1+1 or 3+0). We will conduct surveillance for disease in the 2 weeks to 59 months age group. After allowing time for the potentially different community-level effects of the two schedules to develop, we will measure the percentage of children with clinical pneumonia who have bacteria in their nose of the same type that is prevented by the vaccine. We will also measure the percentage of children aged 6-12 weeks presenting for their 1st dose of PCV, and the percentage of the whole population, who have bacteria in their nose of the same type that is prevented by the vaccine.
What are the possible benefits and risks?
Potential benefits include fewer injections, more simple logistics, and less cost to the government. Potential risks are that pneumococcal disease may be more likely in one group.
Where is the study run from?
The study is located in rural Gambia and run from the Basse field station of the Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine.
When is the study starting and how long is it expected to run for?
November 2018 to May 2024.
Who is funding the study?
The study is funded by the MRC/Wellcome/DFID/NIHR Joint Global Health Trials scheme and the Bill and Melinda Gates Foundation.
Who is the main contact?
Dr Grant Mackenzie, gmackenzie@mrc.gm
Contact information
Scientific
Basse Field Station
MRCG at LSHTM
Basse
NA
Gambia
 ORCID ID |
0000-0002-4994-2627 |
|---|---|
| Phone | +220 5669255 |
| gmackenzie@mrc.gm |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Single-centre cluster-randomised non-inferiority parallel-group unmasked trial |
| Secondary study design | Cluster randomised trial |
| Study type | Participant information sheet |
| Scientific title | A cluster-randomised, non-inferiority trial of the impact of a two-dose compared to a three-dose schedule of pneumococcal conjugate vaccine in rural Gambia. |
| Study acronym | PVS |
| Study objectives | The impact of PCV13 delivered in a 1+1 schedule is non-inferior to a 3+0 schedule. |
| Ethics approval(s) | 1. Gambia Government/MRC Joint Ethics Committee; 19/03/201, L2018.E08, SCC1577v1.2 2. London School of Hygiene & Tropical Medicine Observational/Interventions Research Ethics Committee, 26/02/2018, 14515 |
| Health condition(s) or problem(s) studied | Streptococcus pneumoniae disease and pneumococcal colonisation |
| Intervention | 13-valent pneumococcal conjugate vaccine (PCV13) will be delivered in two schedules, one with doses scheduled at ages 6, 10 and 14 weeks (3+0 schedule) and the other with doses scheduled at ages 6 weeks and 9 months (1+1 schedule). The two schedules will be randomly allocated (1:1) to 68 geographic clusters where children attend one immunisation clinic. |
| Intervention type | Biological/Vaccine |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | 13-valent pneumococcal conjugate vaccine (PCV13) |
| Primary outcome measure(s) |
Nasopharyngeal (NP) carriage of vaccine-type (VT) pneumococci in children aged 2 weeks to 59 months with clinical pneumonia will be measured in the 2nd and 4th year of the trial. Measurement in the 4th year is the primary analysis. Measurement in the 2nd year is a secondary analysis. |
| Key secondary outcome measure(s) |
1. NP carriage of non-vaccine-type (NVT) pneumococci in children aged 2 weeks to 59 months with clinical pneumonia measured in the 4th year of the trial |
| Completion date | 31/05/2024 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Child |
| Lower age limit | 2 Weeks |
| Upper age limit | 59 Months |
| Sex | All |
| Target sample size at registration | 50000 |
| Key inclusion criteria | 1. Resident in the study area 2. Children aged 6 weeks to 365 days will be eligible to receive the intervention 3. Children aged 2 weeks to 59 months will be eligible for measurement of the primary endpoint and disease endpoints by disease surveillance |
| Key exclusion criteria | 1. Intent to move out of the study area before 4 months of age 2. Aged over 364 days 3. Contraindication to vaccination with PCV13, including severe hypersensitivity to a previous dose of PCV13 |
| Date of first enrolment | 22/08/2019 |
| Date of final enrolment | 31/10/2023 |
Locations
Countries of recruitment
- Gambia
Study participating centre
Upper River Region
Basse
NA
Gambia
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | |
| IPD sharing plan | Anonymised datasets will be available indefinitely after publications of results. Data will be accessible by application to the MRCG at LSHTM scientific coordinating committee. Participant consent will be obtained. Approval of the Gambia government/MRCG at LSHTM joint ethics committee is required for data to be sent out of the country. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 24/01/2022 | 24/05/2022 | Yes | No | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Statistical Analysis Plan | statistical analysis plan article | 28/12/2022 | 03/03/2023 | Yes | No |
Editorial Notes
05/12/2023: The overall study end date was changed from 31/12/2023 to 31/05/2024.
03/03/2023: The following changes were made to the trial record:
1. Uploaded statistical analysis plan article.
2. The publication and dissemination plan has been changed.
21/10/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 15/10/2022 to 31/10/2023.
2. The overall end date was changed from 31/12/2022 to 31/12/2023.
3. The intention to publish date was changed from 31/12/2023 to 02/02/2025.
4. The plain English summary was updated to reflect these changes.
24/05/2022: Publication reference added.
06/10/2021: The recruitment start date was changed from 15/11/2018 to 22/08/2019.
21/09/2021: Internal review.
10/07/2020: The following changes have been made:
1. Recruitment has resumed.
2. The trial phase was added.
24/04/2020: Due to current public health guidance, recruitment for this study has been paused.
23/11/2018: Internal review.
