Immunogenicity of PCV-7 Vaccine in VLBW Infants

Sponsor

NICHD Neonatal Research Network (Other)

Overall Status

Completed

CT.gov ID

NCT00273325

Collaborator

National Center for Research Resources (NCRR) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

368

Enrollment

Locations

Duration (Months)

36.8

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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	Intervention/Treatment	Phase
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 Design

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 :

Jul 1, 2004

Actual Primary Completion Date :

Jul 1, 2007

Actual Study Completion Date :

Mar 1, 2009

Outcome Measures

Primary Outcome Measures

Serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml [4-6 weeks following the third dose of PCV-7]

Secondary Outcome Measures

Pneumococcal capsular polysaccharide antibody >=0.15 μg/ml for the other six vaccine serotypes [4-6 weeks following the third dose of PCV-7]
Pneumococcal capsular polysaccharide antibodies >=1.0 μg/ml for all seven vaccine serotypes [4-6 weeks following the third dose of PCV-7]
Geometric mean titers of pneumococcal capsular polysaccharide antibody to the seven vaccine serotypes [4-6 weeks following the third dose of PCV-7]
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 [4-6 weeks following the third dose of PCV-7]
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 [4-6 weeks following the third dose of PCV-7]
Effect of possible mediating variables on the achievement of levels of serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml [4-6 weeks following the third dose of PCV-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 [18-22 months corrected age]
Levels of antibody >=0.15 μg/ml and >=1.0 μg/ml to Hib polyribosylribitol [4-6 weeks following the third dose of PCV-7]
Avidity of antibody to Hib-PRP among infants in the lowest quartile of antibody response,regardless of postnatal or gestational age [4-6 weeks following the third dose of PCV-7]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 3 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Stanford University	Palo Alto	California	United States	94304
3	University of Miami	Miami	Florida	United States	33136
4	Emory University	Atlanta	Georgia	United States	30303
5	Wayne State University	Detroit	Michigan	United States	48201
6	University of Rochester	Rochester	New York	United States	14642
7	Wake Forest University	Charlotte	North Carolina	United States	27157
8	RTI International	Durham	North Carolina	United States	27705
9	Duke University	Durham	North Carolina	United States	27710
10	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