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Effect of Two Versus Three Pneumococcal Conjugate Vaccinations (MNOES)

This study has been completed.
Sponsor:
Collaborators:
Netherlands: Ministry of Health, Welfare and Sports
Netherlands Vaccine Institute
Information provided by (Responsible Party):
Prof Dr EAM Sanders, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT00189020
First received: September 9, 2005
Last updated: August 19, 2011
Last verified: August 2011

September 9, 2005
August 19, 2011
June 2005
February 2008   (final data collection date for primary outcome measure)
  • Nasopharyngeal bacterial (pneumococcal) colonization at 6 weeks, 6, 12, 18 and 24 months in infants and at 12 and 24 months of family members [ Time Frame: duration of study, 23 months per subject ] [ Designated as safety issue: No ]
  • transmission to family members( sib, caregiver) [ Time Frame: at infants age of 12 and 24 months ] [ Designated as safety issue: No ]
nasopharyngeal bacterial (pneumococcal) colonization at 6 weeks, 6, 12, 18 and 24 months in infants and at 12 and 24 months of family members
Complete list of historical versions of study NCT00189020 on ClinicalTrials.gov Archive Site
  • anti-pneumococcal antibody levels at 12 and 24 months of age [ Time Frame: 23 months ] [ Designated as safety issue: No ]
  • antibody levels and B-memory cells after vaccination at 24 months [ Time Frame: 23 months ] [ Designated as safety issue: No ]
  • - anti-pneumococcal antibody levels at 12 and 24 months of age
  • - respiratory tract infections and medication during first 2 years of life
Not Provided
Not Provided
 
Effect of Two Versus Three Pneumococcal Conjugate Vaccinations
Effect of 2 Versus 3 Pneumococcal Conjugate Vaccinations Prevnar on Nasopharyngeal Carriage, Transmission and Herd-immunity;a Randomized, Controlled Study

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

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Streptococcus Pneumoniae Infection
  • Biological: PCV7
    PCV7 at age 2 and 4 months
    Other Name: Prevenar
  • Biological: PCV7
    PCV7 at age 2, 4 and 11 months
    Other Name: Prevenar
  • Experimental: 2-dose
    PCV7 at age 2 and 4 months
    Intervention: Biological: PCV7
  • Experimental: 2+1-dose
    PCV7 at age 2, 4 and 11 months
    Intervention: Biological: PCV7
  • No Intervention: Control
    Control group

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1005
Not Provided
February 2008   (final data collection date for primary outcome measure)

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
Both
2 Months to 3 Months
Yes
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00189020
MINOES 01, STEG R05 008, ISRCTN
Yes
Prof Dr EAM Sanders, UMC Utrecht
UMC Utrecht
  • Netherlands: Ministry of Health, Welfare and Sports
  • Netherlands Vaccine Institute
Principal Investigator: Elisabeth A. M. Sanders, MD, PhD UMC Utrecht
UMC Utrecht
August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP