Effect of Two Versus Three Pneumococcal Conjugate Vaccinations

Streptococcus Pneumoniae Infection Clinical Trial

— MNOES  

Official title:

Effect of 2 Versus 3 Pneumococcal Conjugate Vaccinations Prevnar on Nasopharyngeal Carriage, Transmission and Herd-immunity;a Randomized, Controlled Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00189020
• Other study ID #: MINOES 01, STEG R05 008
• Secondary ID: ISRCTN
• Status: Completed
• Phase: Phase 3
• First received: September 9, 2005
• Last updated: August 19, 2011
• Start date: June 2005

Study information

• Verified date: August 2011
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Dutch Health Care InspectorateNetherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial Summary

Two( 2) or three (3) instead of four vaccinations before the age of 6 months with pneumococcal conjugate vaccine are presumed to protect children against invasive pneumococcal disease like meningitis, at least on the short term till 18-24 months of age. The current hypothesis in this study is 2 or 3 vaccinations will protect against IPD but will not alter pneumococcal nasopharyngeal carriage in infants, and consequently not change pneumococcal transmission and induce no herd-immunity. Furthermore, antibody development and memory may benefit from carriage of vaccine type S. pneumoniae

Description:

Two(2 and 4 months) and three vaccinations (2,4 and 11 months) with 7-valent pneumococcal conjugate vaccine Prevnar in infants are presumed to provide about 90% protection against invasive pneumococcal disease (IPD) for vaccine type pneumococci, at least until 18-24 months of age. Licensure of the vaccine however is based on studies with 3 vaccinations before 6 months and a booster vaccination half a year later (3+1 scheme). Cost-effectiveness in national infant vaccination programs (NIPs)is much improved by high herd-immunity effects,as observed in the USA after licensure of Prevnar in 2000, both for IPD and AOM. However, overall pneumococcal carriage reduction (and nasopharyngeal replacement) has not been assessed in studies with reduced doses. With reduced carriage reduction, effects on respiratory tract infections and herd immunity may be significantly less.

The primary aim of the current study is to compare effect of 2-doses (at ages 2 and 4 months) with a 3-doses scheme(2+1, at 2, 4 and 11 months) on nasopharyngeal pneumococcal carriage and replacement and family transmission(sibs and caregivers), in order to allow modelling for herd-immunity.

The secondary aim is to determine the effect of a reduced doses scheme on serum antipneumococcal antibody levels at the age of 12 and 24 months.

A third aim is to determine antipneumococcal antibody levels and memory B-cell development after booster vaccination at 24 months of age, after 2 or 2+1 doses and compare these with a first vaccination at 24 months of age.

Opportunities are the determination of nasopharyngeal colonizing pneumococci in unvaccinated infants in the Netherlands before implementation of Prevnar in the NIP, evaluation of replacing pneumococci in the nasopharynx after vaccinations and analysis of effects on other colonizing bacteria like H.influenzae, M. catarrhalis and S.aureus. Furthermore, the relation between colonizing pneumococci and serotypes causing IPD in the Netherlands can be evaluated.

Methods : 1000 infants and families will be included in a randomized,controlled study with 3 interventions groups

1. Prevnar at 2 and 4 months

2. Prevnar at 2, 4 and 11 months

3. Prevnar at 24 months (controls)

The children will be followed until 2 years of age with nasopharyngeal swabs for bacterial culture before the first vaccination, at 6, 12, 18 and 24 months of age. One sibling and one parent/caregiver will be swabbed when the infant is 12 and 24 months. Blood for antibody determination will be obtained from 80 children of groups 1 and 2, and from 30 children in the control group. Questionnaires on health and respiratory infections and antibiotic prescription for RTI will be obtained.

At 24 months of age, all children of groups 1 and 2 will be offered a booster vaccination. Antibody levels will be measured before and 4 weeks after this vaccination at 2 years of age in a subset of 80 children per group and compared with 80 children who received a first vaccination at 24 months of age.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1005
• Est. primary completion date: February 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 2 Months to 3 Months

Eligibility

Inclusion Criteria:

• Newborn infants eligible for participation in the national infant vaccination program in the Netherlands

Exclusion Criteria:

exclusion from the national vaccination program because of the presence of

• a medical condition requiring treatment that can interfere with the effect of vaccinations

• known or suspected allergy to components of the pneumococcal conjugate vaccine

• known or suspected immunodeficiency disease

• previous treatment with plasma or immunoglobulins

• previous vaccinations other than hepatitis B vaccinations

• coagulation disorders

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Pneumococcal Infections
• Streptococcus Pneumoniae Infection

Intervention

Biological:
• PCV7
PCV7 at age 2 and 4 months
• PCV7
PCV7 at age 2, 4 and 11 months

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
UMC Utrecht	Netherlands Vaccine Institute, Netherlands: Ministry of Health, Welfare and Sports

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nasopharyngeal bacterial (pneumococcal) colonization at 6 weeks, 6, 12, 18 and 24 months in infants and at 12 and 24 months of family members		duration of study, 23 months per subject	No
Primary	transmission to family members( sib, caregiver)		at infants age of 12 and 24 months	No
Secondary	anti-pneumococcal antibody levels at 12 and 24 months of age		23 months	No
Secondary	antibody levels and B-memory cells after vaccination at 24 months		23 months	No