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
  Purpose

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


Condition Intervention Phase
Streptococcus Pneumoniae Infection
Biological: PCV7
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effect of 2 Versus 3 Pneumococcal Conjugate Vaccinations Prevnar on Nasopharyngeal Carriage, Transmission and Herd-immunity;a Randomized, Controlled Study

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 1005
Study Start Date: June 2005
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2-dose
PCV7 at age 2 and 4 months
Biological: PCV7
PCV7 at age 2 and 4 months
Other Name: Prevenar
Experimental: 2+1-dose
PCV7 at age 2, 4 and 11 months
Biological: PCV7
PCV7 at age 2, 4 and 11 months
Other Name: Prevenar
No Intervention: Control
Control group

Detailed 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.

  Eligibility

Ages Eligible for Study:   2 Months to 3 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00189020

Sponsors and Collaborators
UMC Utrecht
Netherlands: Ministry of Health, Welfare and Sports
Netherlands Vaccine Institute
Investigators
Principal Investigator: Elisabeth A. M. Sanders, MD, PhD UMC Utrecht
  More Information

No publications provided by UMC Utrecht

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Prof Dr EAM Sanders, prof. dr., UMC Utrecht
ClinicalTrials.gov Identifier: NCT00189020     History of Changes
Other Study ID Numbers: MINOES 01, STEG R05 008, ISRCTN
Study First Received: September 9, 2005
Last Updated: August 19, 2011
Health Authority: Netherlands: Dutch Health Care Inspectorate
Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by UMC Utrecht:
pneumococcal conjugate vaccination
nasopharyngeal carriage
herd immunity
antipneumococcal antibodies
respiratory tract infections
National infant vaccination program

Additional relevant MeSH terms:
Infection
Pneumococcal Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Streptococcal Infections

ClinicalTrials.gov processed this record on October 22, 2014