Condition category
Infections and Infestations
Date applied
04/08/2004
Date assigned
22/09/2004
Last edited
13/09/2007
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Thomas Cherian

ORCID ID

Contact details

World Health Organization
20 Avenue Appia
Geneva-27
CH-1211
Switzerland
cheriant@who.int

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

WHO/RPC028

Study information

Scientific title

Acronym

Study hypothesis

Current hypothesis as of 13/09/2007:
In Kenyan children under 2 years of age, 23% of deaths from invasive pneumococcal disease occur in the first 14 weeks of life. Expanded Programme on Immunisation (EPI) vaccines are administered at 6, 10 and 14 weeks. Earlier vaccination against pneumococcus may prevent deaths of very young infants. This study examines whether 7-valent Pneumococcal Conjugate Vaccine (PCV) given on the first 72 hours of life is safe and whether it provides an adequate immunological response, including development of immunological memory, when compared to a regime in which the first dose is given at 6 weeks. 300 children will be randomised to one of two regimes; PCV at birth (up to 72 hours), 10 and 14 weeks or PCV at 6, 10 and 14 weeks. The safety and basic immunogenicity data will be analysed after a first phase of 60 children and a further phase of 240 children will be recruited if the results are found to be satisfactory.

Please note that the change to this hypothesis was made due to an initial protocol modification, where the 'birth' dose was amended from 24 hours to 72 hours. No other area of this trial was amended.

Previous hypothesis:
In Kenyan children under 2 years of age, 23% of deaths from invasive pneumococcal disease occur in the first 14 weeks of life. Expanded Programme on Immunisation (EPI) vaccines are administered at 6, 10 and 14 weeks. Earlier vaccination against pneumococcus may prevent deaths of very young infants. This study examines whether 7-valent Pneumococcal Conjugate Vaccine (PCV) given on the first day of life is safe and whether it provides an adequate immunological response, including development of immunological memory, when compared to a regime in which the first dose is given at 6 weeks. 300 children will be randomised to one of two regimes; PCV at birth, 10 and 14 weeks or PCV at 6, 10 and 14 weeks. The safety and basic immunogenicity data will be analysed after a first phase of 60 children and a further phase of 240 children will be recruited if the results are found to be satisfactory.

Ethics approval

Ethics approval received from:
1. Kenya Medical Research Institute (KEMRI)/National Ethical Review Committee on the 27th October 2003
2. World Health Organization (WHO) Ethics Review Committee on the 18th September 2003 (renewed annually)

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Condition

Pneumococcus/vaccines

Intervention

Infants will receive 7-valent conjugate pneumococcal vaccine (PCV7) at birth (up to 72 hours - see point mentioned in hypothesis above), 6 and 10 weeks (group 1) or at 6, 10 and 14 weeks (group 2) along with routine Expanded Program of Immunisation (EPI) vaccines. Infants in each group will be randomised to receive either PCV7 or 23-valent pneumococcal polysaccharide vaccine at 9 months of age. Blood will be collected for measurement of antibody response prior to vaccine, 4 weeks after the primary series and pre- and 4 weeks post-booster dose. All infants will have Nasopharyngeal (NP) swabs collected at 18 weeks and 9 months of age that will be cultured for pneumococcus.

Intervention type

Drug

Phase

Not Specified

Drug names

Pneumococcal Conjugate Vaccine (PCV)

Primary outcome measures

1. Clinical safety data in children vaccinated at birth compared to children vaccinated first at 6 weeks of life
2. Immunogenicity as measured by anti-capsular Immunoglobulin G (IgG) Enzyme-Linked Immuno-Sorbent Assay (ELISA) to serotypes in the vaccine, measured after a complete primary course at 18 weeks.

Secondary outcome measures

1. Immunogenicity as measured by anti-capsular IgG ELISA after one or two doses of vaccine, of which one was given at birth
2. Immunological memory measured as IgG response to a booster vaccine dose (either PCV or 1/5th dose pneumococcal polysaccharide vaccine with a 50% probability of each) at 36 weeks
3. Functional immune response to first vaccination at birth as measured by prevalence of nasopharyngeal colonisation with S. pneumoniae at 18 and 36 weeks
4. Interference with immune response to diphtheria and tetanus attributable to vaccination with PCV at birth as measured by diphtheria and tetanus antibody concentration at 18 weeks
5. Interference with immune response to measles vaccine given at 36 weeks measured by anti-measles antibodies at 37 weeks
6. Effect of (maternal) pre-existing pneumococcal, diphtheria and tetanus antibody levels at birth on immune response to the primary course of PCV, and Diphtheria Pertussis Tetanus (DPT) vaccine.

Overall trial start date

01/11/2004

Overall trial end date

31/10/2006

Reason abandoned

Eligibility

Participant inclusion criteria

1. Healthy infants born to mothers tested human immunodeficiency virus (HIV) negative in the voluntary counselling and testing service
2. Not known to have congenital immune deficiency
3. Birth weight greater than 2500 g
4. Informed consent

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

300

Participant exclusion criteria

1. Infants requiring ongoing hospitalisation after birth
2. Suspected immune deficiency
3. Participation in another clinical trial

Any child who suffers a serious adverse event directly attributable to pneumococcal vaccination will be excluded from continued participation.

Recruitment start date

01/11/2004

Recruitment end date

31/10/2006

Locations

Countries of recruitment

Kenya

Trial participating centre

World Health Organization
Geneva-27
CH-1211
Switzerland

Sponsor information

Organisation

Kenya Medical Research Institute (Kenya)

Sponsor details

PO Box 54840
Nairobi
-
Kenya

Sponsor type

Research organisation

Website

http://www.kemri.org/

Funders

Funder type

Research organisation

Funder name

World Health Organization (WHO)/Department of Immunisation, Vaccines and Biologicals (IVB) (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes