Pneumococcal Vaccine Schedules (PVS)

ISRCTN	ISRCTN15056916
DOI	https://doi.org/10.1186/ISRCTN15056916
Secondary identifying numbers	SCC 1577 v1.2

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

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

Dr Grant Mackenzie
Scientific

Basse Field Station
MRCG at LSHTM
Basse
NA
Gambia

ORCID ID	0000-0002-4994-2627
Phone	+220 5669255
Email	gmackenzie@mrc.gm

Study information

Study design	Single-centre cluster-randomised non-inferiority parallel-group unmasked trial
Primary study design	Interventional
Secondary study design	Cluster randomised trial
Study setting(s)	Community
Study type	Prevention
Participant information sheet	Not available in web format.
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
Pharmaceutical study type(s)	Not Applicable
Phase	Phase IV
Drug / device / biological / vaccine name(s)	13-valent pneumococcal conjugate vaccine (PCV13)
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 study start date	09/06/2017
Completion date	31/05/2024

Eligibility

Participant type(s)	Mixed
Age group	Child
Lower age limit	2 Weeks
Upper age limit	59 Months
Sex	Both
Target number of participants	68 clusters; birth cohort approximately 10,000 per year
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

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

London School of Hygiene & Tropical Medicine
University/education

Keppel Street
London
WC1E 7HT
England
United Kingdom

Website	https://www.lshtm.ac.uk
"ROR"	https://ror.org/00a0jsq62

Funders

Funder type

Research council

Medical Research Council
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

Wellcome Trust
Private sector organisation / International organizations

Location: United Kingdom

Department for International Development
Government organisation / National government

Alternative name(s): Department for International Development, UK, DFID
Location: United Kingdom

National Institute for Health Research
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Bill and Melinda Gates Foundation
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	02/02/2025
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Stored in repository
Publication and dissemination plan	Current publication and dissemination plan as of 03/03/2023: The protocol and statistical analysis plan were published in a peer-reviewed open-access journal in 2022. The final results will be published in a peer-reviewed open-access journal in 2025. Previous publication and dissemination plan: The protocol will be published in a peer-reviewed open-access journal in 2020. The final results will be published in a peer-reviewed open-access journal in 2023.
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
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.