Condition category
Infections and Infestations
Date applied
19/09/2018
Date assigned
15/11/2018
Last edited
23/11/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

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

https://www.lshtm.ac.uk

Funders

Funder type

Research council

Funder name

Medical Research Council

Alternative name(s)

MRC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Funder name

Wellcome Trust

Alternative name(s)

Wellcome

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Funder name

Department for International Development

Alternative name(s)

Department for International Development, UK, DFID

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

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

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

Publication citations

Additional files

Editorial Notes

23/11/2018: Internal review.