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Immunogenicity of PCV-7 Vaccine in VLBW Infants (PCV-7)

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ClinicalTrials.gov Identifier: NCT00273325
Recruitment Status : Completed
First Posted : January 9, 2006
Last Update Posted : September 26, 2017
Sponsor:
Collaborators:
National Center for Research Resources (NCRR)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
NICHD Neonatal Research Network

Brief Summary:
Premature infants are at a high risk for pneumonia. The PCV-7 vaccine effectively prevents the invasive disease from Streptococcus pneumoniae in full-term infants, but was not thoroughly studied in premature infants. This study evaluated the effectiveness and safety of the vaccine given in routine practice to very low birth weight infants, looking at blood antibody levels 4-6 weeks after the final vaccine dose, and adverse events, survival, infections, and neurodevelopmental outcomes at 18-22 months corrected age.

Condition or disease
Pneumococcal Infections Streptococcus Pneumoniae Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature

Detailed Description:

Streptococcus pneumoniae causes an estimated 10-25% of all pneumonias in the United States, and is responsible for an estimated 40,000 deaths per year. Invasive pneumococcal disease has a peak incidence of 235/100,000 among children aged 6-11 months. Pneumococcal meningitis carries a higher risk of death (15%) or neurodevelopmental impairment (12-28%) than Hib or Neisseria meningitides.

Premature infants are at a higher risk for invasive disease with Streptococcus pneumoniae. The heptavalent pneumococcal-CRM197 conjugate vaccine (PCV-7) effectively prevents invasive pneumococcal disease in full-term infants, but was been incompletely studied in premature infants. The American Academy of Pediatrics (AAP) recommends that "prematurely born infants, including infants of low birth weight, should be immunized at the usual chronological age in most cases", but cautions that "some studies suggest a reduced immune response in very low-birth-weight infants (<1500 g)."

This observational study assessed the effectiveness of the PCV-7 vaccine to generate a sufficient immune response in a safe manner when given to very low birth weight (VLBW) infants in routine pediatric practice. We hypothesized that among VLBW infants, the frequency of estimated minimum protective antibody titers to PCV-7 (>=0.15 μg/mL) would decrease with decreasing birth weight.

Infants 501-1500g birth weight and <32 0/7 weeks gestational age were enrolled from nine NICHD Neonatal Research Network centers from 2004 to 2006. Enrollment was stratified by weight group to yield approximately 20 infants per 100g increments from 501-1500g birth weight whose primary PCV-7 series was initiated before 3 months and completed by 8 months after birth. The infants' primary providers gave PCV-7 vaccination at 2, 4, and 6 months after birth. Infants had a single 2-ml blood sample drawn 4-6 weeks following the third dose of PCV-7. Antibodies for each of the seven vaccine serotypes included in PCV-7 were measured by enzyme-linked immunosorbent assay. Children were followed until 18-22 months corrected age to assess survival, infection, and neurodevelopmental outcomes.


Study Type : Observational
Actual Enrollment : 368 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Observational Study of the Immunogenicity of Heptavalent Pneumococcal Conjugate Vaccine in Very-low-birth-weight Infants
Study Start Date : July 2004
Actual Primary Completion Date : July 2007
Actual Study Completion Date : March 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Birth Weight




Primary Outcome Measures :
  1. Serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]

Secondary Outcome Measures :
  1. Pneumococcal capsular polysaccharide antibody >=0.15 μg/ml for the other six vaccine serotypes [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
  2. Pneumococcal capsular polysaccharide antibodies >=1.0 μg/ml for all seven vaccine serotypes [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
  3. Geometric mean titers of pneumococcal capsular polysaccharide antibody to the seven vaccine serotypes [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
  4. Pneumococcal capsular polysaccharide antibodies >=0.15 μg/ml and >=1.0 μg/ml, and geometric mean titers of antibody, to the seven vaccine serotypes in children completing the primary series, regardless of postnatal age [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
  5. Opsonization of 6B pneumococcal capsular polysaccharide plus 1 low immunogenicity, high prevalence serotype (e.g., 23F) among infants in the lowest quartile of antibody response [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
  6. Effect of possible mediating variables on the achievement of levels of serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
  7. Effect of pneumococcal conjugate immunization status (complete & timely v. complete v. incomplete) on outcome (survival, serious infection, neurodevelopmental outcome) at 18-22 months corrected age in infants <=1000g [ Time Frame: 18-22 months corrected age ]
  8. Levels of antibody >=0.15 μg/ml and >=1.0 μg/ml to Hib polyribosylribitol [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
  9. Avidity of antibody to Hib-PRP among infants in the lowest quartile of antibody response,regardless of postnatal or gestational age [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]

Biospecimen Retention:   Samples With DNA
Serum was separated from blood samples. After all study assays were completed on all subjects, if a subject's parents asked that his/her serum not be stored, the serum was destroyed. For subjects whose parents permit it, leftover serum was re-labeled with a new, randomly-generated unique de-identifier, linked only to the subject's gestational age, birth weight, and chronologic age at the time of sampling. The link to any other subject identifiers will then be destroyed. The serum will be stored indefinitely at the University of Rochester for other, non-genetic-testing-related research.


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Ages Eligible for Study:   up to 3 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Infants <1,500g birth weight who receive the 3-dose primary series of PCV-7 immunization by 3 months and complete it by 8 months postnatal age
Criteria

Inclusion criteria

  • Gestational age <32 0/7 weeks
  • Included in Neonatal Research Network Generic Database
  • Family has a telephone at home
  • Anticipated availability for blood draw 4-6 weeks following 3rd vaccine dose
  • Consent obtained before first dose of PCV-7 is given

Exclusion criteria

  • Known immunodeficiency
  • HIV exposure
  • Parental non-consent
  • Primary care pediatrician not willing to participate
  • Enrollment in a conflicting trial
  • Infant has not received first dose of PCV-7 vaccine by 3 months of age

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00273325


Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, North Carolina
Wake Forest University
Charlotte, North Carolina, United States, 27157
RTI International
Durham, North Carolina, United States, 27705
Duke University
Durham, North Carolina, United States, 27710
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
Sponsors and Collaborators
NICHD Neonatal Research Network
National Center for Research Resources (NCRR)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Ronald N. Goldberg, MD Duke University
Principal Investigator: Barbara J. Stoll, MD Emory University
Principal Investigator: Abhik Das, PhD RTI International
Principal Investigator: Krisa P. Van Meurs, MD Stanford University
Principal Investigator: Waldemar A. Carlo, MD University of Alabama at Birmingham
Principal Investigator: Shahnaz Duara, MD University of Miami
Principal Investigator: Carl T. D'Angio, MD University of Rochester
Principal Investigator: Pablo J. Sanchez, MD University of Texas, Southwestern Medical Center at Dallas
Principal Investigator: T. Michael O`Shea, MD MPH Wake Forest University
Principal Investigator: Seetha Shankaran, MD Wayne State University

Additional Information:
Publications of Results:

Responsible Party: NICHD Neonatal Research Network
ClinicalTrials.gov Identifier: NCT00273325     History of Changes
Other Study ID Numbers: NICHD-NRN-0031
UL1RR024128 ( U.S. NIH Grant/Contract )
UL1RR024160 ( U.S. NIH Grant/Contract )
UL1RR024982 ( U.S. NIH Grant/Contract )
UL1RR025008 ( U.S. NIH Grant/Contract )
UL1RR025744 ( U.S. NIH Grant/Contract )
UL1RR025777 ( U.S. NIH Grant/Contract )
M01RR016587 ( U.S. NIH Grant/Contract )
M01RR000030 ( U.S. NIH Grant/Contract )
M01RR000032 ( U.S. NIH Grant/Contract )
M01RR000039 ( U.S. NIH Grant/Contract )
M01RR000044 ( U.S. NIH Grant/Contract )
M01RR000633 ( U.S. NIH Grant/Contract )
M01RR000070 ( U.S. NIH Grant/Contract )
M01RR007122 ( U.S. NIH Grant/Contract )
U01HD036790 ( U.S. NIH Grant/Contract )
U10HD021385 ( U.S. NIH Grant/Contract )
U10HD021397 ( U.S. NIH Grant/Contract )
U10HD027851 ( U.S. NIH Grant/Contract )
U10HD027880 ( U.S. NIH Grant/Contract )
U10HD034216 ( U.S. NIH Grant/Contract )
U10HD040492 ( U.S. NIH Grant/Contract )
U10HD040498 ( U.S. NIH Grant/Contract )
U10HD040521 ( U.S. NIH Grant/Contract )
U10HD040689 ( U.S. NIH Grant/Contract )
First Posted: January 9, 2006    Key Record Dates
Last Update Posted: September 26, 2017
Last Verified: September 2017

Keywords provided by NICHD Neonatal Research Network:
NICHD Neonatal Research Network
Very Low Birth Weight (VLBW)
Extremely Low Birth Weight (ELBW)
Prematurity
Pneumococcal Vaccines
Vaccines, Conjugate
Immunogenicity
Vaccine Response
Heptavalent pneumococcal conjugate vaccine (PCV-7)
pneumococcal polysaccharide, type 6B
Pneumococcal polysaccharide, type 14
Pneumococcal polysaccharide, type 19F,
Pneumococcal polysaccharide, 23F
Pneumococcal polysaccharide, 18C
Pneumococcal polysaccharide, 4
Pneumococcal polysaccharide, 9V

Additional relevant MeSH terms:
Pneumonia
Birth Weight
Pneumococcal Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Body Weight
Signs and Symptoms
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs