Immunogenicity of PCV-7 Vaccine in VLBW Infants

Pneumococcal Infections Clinical Trial

— PCV-7  

Official title:

Observational Study of the Immunogenicity of Heptavalent Pneumococcal Conjugate Vaccine in Very-low-birth-weight Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00273325
• Other study ID #: NICHD-NRN-0031
• Secondary ID: UL1RR024128UL1RR
• Status: Completed
• Start date: July 2004
• Est. completion date: March 2009

Study information

• Verified date: March 2019
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 368
• Est. completion date: March 2009
• Est. primary completion date: July 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 3 Months

Eligibility

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

Related Conditions & MeSH terms

• Birth Weight
• Infant, Low Birth Weight
• Infant, Newborn
• Infant, Premature
• Infant, Small for Gestational Age
• Pneumococcal Infections
• Pneumonia
• Streptococcus Pneumoniae

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Wake Forest University	Charlotte	North Carolina
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	RTI International	Durham	North Carolina
United States	University of Miami	Miami	Florida
United States	Stanford University	Palo Alto	California
United States	University of Rochester	Rochester	New York

Sponsors (3)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Ang JY, Lua JL, Asmar BI, Shankaran S, Heyne RJ, Schelonka RL, Das A, Li L, Jackson DM, Higgins RD, D'Angio CT; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Nasopharyngeal carriage of Streptoco — View Citation

D'Angio CT, Heyne RJ, O'Shea TM, Schelonka RL, Shankaran S, Duara S, Goldberg RN, Stoll BJ, Van Meurs KP, Vohr BR, Das A, Li L, Burton RL, Hastings B, Phelps DL, Sanchez PJ, Carlo WA, Stevenson DK, Higgins RD; NICHD Neonatal Research Network. Heptavalent — View Citation

D'Angio CT, Murray TE, Li L, Heyne RJ, O'Shea TM, Schelonka RL, Shankaran S, Duara S, Goldberg RN, Stoll BJ, Stevenson DK, Vohr BR, Phelps DL, Carlo WA, Pichichero ME, Das A, Higgins RD; NICHD Neonatal Research Network. Immunogenicity of Haemophilus influ — View Citation

Wynn JL, Li L, Cotten CM, Phelps DL, Shankaran S, Goldberg RN, Carlo WA, Van Meurs K, Das A, Vohr BR, Higgins RD, Stoll BJ, D'Angio CT. Blood stream infection is associated with altered heptavalent pneumococcal conjugate vaccine immune responses in very l — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 µg/ml		4-6 weeks following the third dose of PCV-7
Secondary	Pneumococcal capsular polysaccharide antibody >=0.15 µg/ml for the other six vaccine serotypes		4-6 weeks following the third dose of PCV-7
Secondary	Pneumococcal capsular polysaccharide antibodies >=1.0 µg/ml for all seven vaccine serotypes		4-6 weeks following the third dose of PCV-7
Secondary	Geometric mean titers of pneumococcal capsular polysaccharide antibody to the seven vaccine serotypes		4-6 weeks following the third dose of PCV-7
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   NICHD Neonatal Research Network