Effect of Two Versus Three Pneumococcal Conjugate Vaccinations (MNOES)

August 19, 2011 updated by: Prof Dr EAM Sanders, UMC Utrecht

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1005

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 months to 3 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
Control group
Experimental: 2-dose
PCV7 at age 2 and 4 months
Biological: PCV7
PCV7 at age 2 and 4 months
Other Names:
  • Prevenar
Biological: PCV7
PCV7 at age 2, 4 and 11 months
Other Names:
  • Prevenar
Experimental: 2+1-dose
PCV7 at age 2, 4 and 11 months
Biological: PCV7
PCV7 at age 2 and 4 months
Other Names:
  • Prevenar
Biological: PCV7
PCV7 at age 2, 4 and 11 months
Other Names:
  • Prevenar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
duration of study, 23 months per subject
transmission to family members( sib, caregiver)
Time Frame: at infants age of 12 and 24 months
at infants age of 12 and 24 months

Secondary Outcome Measures

Outcome Measure
Time Frame
anti-pneumococcal antibody levels at 12 and 24 months of age
Time Frame: 23 months
23 months
antibody levels and B-memory cells after vaccination at 24 months
Time Frame: 23 months
23 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UMC Utrecht

Collaborators

Netherlands: Ministry of Health, Welfare and Sports
Netherlands Vaccine Institute

Investigators

  • Principal Investigator: Elisabeth A. M. Sanders, MD, PhD, UMC Utrecht

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2005

Primary Completion (Actual)

February 1, 2008

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (Estimate)

September 16, 2005

Study Record Updates

Last Update Posted (Estimate)

August 22, 2011

Last Update Submitted That Met QC Criteria

August 19, 2011

Last Verified

August 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MINOES 01, STEG R05 008
  • ISRCTN (Registry Identifier: ISRCTN11460478)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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