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Effect of Two Versus Three Pneumococcal Conjugate Vaccinations (MNOES)

Primary Purpose

Streptococcus Pneumoniae Infection

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
PCV7
PCV7
Sponsored by
UMC Utrecht
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Streptococcus Pneumoniae Infection focused on measuring pneumococcal conjugate vaccination, nasopharyngeal carriage, herd immunity, antipneumococcal antibodies, respiratory tract infections, National infant vaccination program

Eligibility Criteria

2 Months - 3 Months (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    No Intervention

    Arm Label

    2-dose

    2+1-dose

    Control

    Arm Description

    PCV7 at age 2 and 4 months

    PCV7 at age 2, 4 and 11 months

    Control group

    Outcomes

    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
    transmission to family members( sib, caregiver)

    Secondary Outcome Measures

    anti-pneumococcal antibody levels at 12 and 24 months of age
    antibody levels and B-memory cells after vaccination at 24 months

    Full Information

    First Posted
    September 9, 2005
    Last Updated
    August 19, 2011
    Sponsor
    UMC Utrecht
    Collaborators
    Netherlands: Ministry of Health, Welfare and Sports, Netherlands Vaccine Institute
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00189020
    Brief Title
    Effect of Two Versus Three Pneumococcal Conjugate Vaccinations
    Acronym
    MNOES
    Official Title
    Effect of 2 Versus 3 Pneumococcal Conjugate Vaccinations Prevnar on Nasopharyngeal Carriage, Transmission and Herd-immunity;a Randomized, Controlled Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2011
    Overall Recruitment Status
    Completed
    Study Start Date
    June 2005 (undefined)
    Primary Completion Date
    February 2008 (Actual)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    UMC Utrecht
    Collaborators
    Netherlands: Ministry of Health, Welfare and Sports, Netherlands Vaccine Institute

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief 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
    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 Prevnar at 2 and 4 months Prevnar at 2, 4 and 11 months 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Streptococcus Pneumoniae Infection
    Keywords
    pneumococcal conjugate vaccination, nasopharyngeal carriage, herd immunity, antipneumococcal antibodies, respiratory tract infections, National infant vaccination program

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    Outcomes Assessor
    Allocation
    Randomized
    Enrollment
    1005 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    2-dose
    Arm Type
    Experimental
    Arm Description
    PCV7 at age 2 and 4 months
    Arm Title
    2+1-dose
    Arm Type
    Experimental
    Arm Description
    PCV7 at age 2, 4 and 11 months
    Arm Title
    Control
    Arm Type
    No Intervention
    Arm Description
    Control group
    Intervention Type
    Biological
    Intervention Name(s)
    PCV7
    Other Intervention Name(s)
    Prevenar
    Intervention Description
    PCV7 at age 2 and 4 months
    Intervention Type
    Biological
    Intervention Name(s)
    PCV7
    Other Intervention Name(s)
    Prevenar
    Intervention Description
    PCV7 at age 2, 4 and 11 months
    Primary Outcome Measure Information:
    Title
    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
    Title
    transmission to family members( sib, caregiver)
    Time Frame
    at infants age of 12 and 24 months
    Secondary Outcome Measure Information:
    Title
    anti-pneumococcal antibody levels at 12 and 24 months of age
    Time Frame
    23 months
    Title
    antibody levels and B-memory cells after vaccination at 24 months
    Time Frame
    23 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    2 Months
    Maximum Age & Unit of Time
    3 Months
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Elisabeth A. M. Sanders, MD, PhD
    Organizational Affiliation
    UMC Utrecht
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    25329446
    Citation
    Biesbroek G, Tsivtsivadze E, Sanders EA, Montijn R, Veenhoven RH, Keijser BJ, Bogaert D. Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Am J Respir Crit Care Med. 2014 Dec 1;190(11):1283-92. doi: 10.1164/rccm.201407-1240OC.
    Results Reference
    derived
    PubMed Identifier
    24921688
    Citation
    Biesbroek G, Bosch AA, Wang X, Keijser BJ, Veenhoven RH, Sanders EA, Bogaert D. The impact of breastfeeding on nasopharyngeal microbial communities in infants. Am J Respir Crit Care Med. 2014 Aug 1;190(3):298-308. doi: 10.1164/rccm.201401-0073OC.
    Results Reference
    derived
    PubMed Identifier
    24447437
    Citation
    Biesbroek G, Wang X, Keijser BJ, Eijkemans RM, Trzcinski K, Rots NY, Veenhoven RH, Sanders EA, Bogaert D. Seven-valent pneumococcal conjugate vaccine and nasopharyngeal microbiota in healthy children. Emerg Infect Dis. 2014 Feb;20(2):201-10. doi: 10.3201/eid2002.131220.
    Results Reference
    derived
    PubMed Identifier
    24120678
    Citation
    van Westen E, Rodenburg GD, van Gils EJ, Tcherniaeva I, Berbers GA, Cowell L, Goldblatt D, Rots NY, van den Dobbelsteen GP, Sanders EA. Levels and functionality of antibodies after pneumococcal conjugate vaccine in schedules with different timing of the booster dose. Vaccine. 2013 Dec 2;31(49):5834-42. doi: 10.1016/j.vaccine.2013.09.073. Epub 2013 Oct 10.
    Results Reference
    derived
    PubMed Identifier
    21813135
    Citation
    Rodenburg GD, van Gils EJ, Veenhoven RH, Bogaert D, van den Dobbelsteen GP, Berbers GA, Sanders EA. Lower immunoglobulin G antibody responses to pneumococcal conjugate vaccination at the age of 2 years after previous nasopharyngeal carriage of Streptococcus pneumoniae. J Pediatr. 2011 Dec;159(6):965-70.e1. doi: 10.1016/j.jpeds.2011.06.011. Epub 2011 Aug 2.
    Results Reference
    derived
    PubMed Identifier
    21695210
    Citation
    van Gils EJ, Hak E, Veenhoven RH, Rodenburg GD, Bogaert D, Bruin JP, van Alphen L, Sanders EA. Effect of seven-valent pneumococcal conjugate vaccine on Staphylococcus aureus colonisation in a randomised controlled trial. PLoS One. 2011;6(6):e20229. doi: 10.1371/journal.pone.0020229. Epub 2011 Jun 10.
    Results Reference
    derived
    PubMed Identifier
    20823436
    Citation
    van Gils EJ, Veenhoven RH, Hak E, Rodenburg GD, Keijzers WC, Bogaert D, Trzcinski K, Bruin JP, van Alphen L, van der Ende A, Sanders EA. Pneumococcal conjugate vaccination and nasopharyngeal acquisition of pneumococcal serotype 19A strains. JAMA. 2010 Sep 8;304(10):1099-106. doi: 10.1001/jama.2010.1290.
    Results Reference
    derived
    PubMed Identifier
    19584345
    Citation
    van Gils EJ, Veenhoven RH, Hak E, Rodenburg GD, Bogaert D, Ijzerman EP, Bruin JP, van Alphen L, Sanders EA. Effect of reduced-dose schedules with 7-valent pneumococcal conjugate vaccine on nasopharyngeal pneumococcal carriage in children: a randomized controlled trial. JAMA. 2009 Jul 8;302(2):159-67. doi: 10.1001/jama.2009.975.
    Results Reference
    derived

    Learn more about this trial

    Effect of Two Versus Three Pneumococcal Conjugate Vaccinations

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