Plain English Summary
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 ending?
The study will begin in November 2018 and end in October 2022.
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
Trial website
Contact information
Type
Scientific
Primary contact
Dr Grant Mackenzie
ORCID ID
http://orcid.org/0000-0002-4994-2627
Contact details
Basse Field Station
MRCG at LSHTM
Basse
NA
Gambia
+220 5669255
gmackenzie@mrc.gm
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
SCC 1577 v1.2
Study information
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.
Acronym
PVS
Study hypothesis
The impact of PCV13 delivered in a 1+1 schedule is non-inferior to a 3+0 schedule.
Ethics approval
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
Study design
Single-centre cluster-randomised non-inferiority parallel-group unmasked trial
Primary study design
Interventional
Secondary study design
Cluster randomised trial
Trial setting
Community
Trial type
Prevention
Patient information sheet
Not available in web format.
Condition
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 names
Primary outcome measure
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.
Secondary outcome measures
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
2. Population-based NP prevalence of VT and NVT pneumococci
3. NP prevalence of VT and NVT pneumococci in infants presenting for the first dose of PCV aged 6-12 weeks measured in the 4th year of the trial
4. Incidence of radiological pneumonia in children aged 2 weeks to 59 months will be measured by facility-based surveillance throughout the trial
5. Incidence of clinical pneumonia in children aged 2 weeks to 59 months will be measured by facility-based surveillance throughout the trial
6. Incidence of serotype-specific invasive pneumococcal disease (IPD in children aged 2 weeks to 59 months will be measured by facility-based surveillance throughout the trial
7. Incidence of hospitalisation in children aged 2 weeks to 59 months will be measured by facility-based surveillance throughout the trial
8. Mortality in children aged 2 weeks to 59 months will be measured by facility-based and demographic surveillance throughout the trial
Overall trial start date
09/06/2017
Overall trial end date
31/12/2022
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Mixed
Age group
Child
Gender
Both
Target number of participants
68 clusters; birth cohort approximately 10,000 per year
Participant 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
Recruitment start date
15/11/2018
Recruitment end date
15/10/2022
Locations
Countries of recruitment
Gambia
Trial participating centre
Basse Field Station, Medical Research Council Unit The Gambia at London School of Hygiene & Tropical Medicine
Basse Field Station, MRCG at LSHTM
Upper River Region
Basse
NA
Gambia
Sponsor information
Organisation
London School of Hygiene & Tropical Medicine
Sponsor details
Keppel Street
London
WC1E 7HT
United Kingdom
Sponsor type
Research organisation
Website
Funders
Funder type
Research council
Funder name
Medical Research Council
Alternative name(s)
MRC
Funding Body Type
unknown
Funding Body Subtype
Location
Funder name
Wellcome Trust
Alternative name(s)
Funding Body Type
unknown
Funding Body Subtype
Location
Funder name
Department for International Development
Alternative name(s)
Department for International Development, UK, DFID
Funding Body Type
unknown
Funding Body Subtype
Location
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
unknown
Funding Body Subtype
Location
Funder name
Bill and Melinda Gates Foundation
Alternative name(s)
Funding Body Type
unknown
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
The protocol will be published in a peer-reviewed open-access journal in 2020. Final results will be published in a peer-reviewed open-access journal in 2023.
IPD sharing statement:
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.
Intention to publish date
31/12/2023
Participant level data
Stored in repository
Basic results (scientific)
Publication list