Pneumococcal InfectionsPCV-7NCT00273325
Immunogenicity of PCV-7 Vaccine in VLBW Infants
An observational study of Pneumococcal Infections and Streptococcus Pneumoniae, run by NICHD Neonatal Research Network at 10 sites in United States.
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. Read more about this study
- Who is it for?
- Ages Up to 3 monthsHealthy volunteers can take part
- Conditions the study is for
- Pneumococcal Infections, Streptococcus Pneumoniae, Infant, Newborn
- How many people
- 368 participants
- Where
- 10 sitesUnited States
- Study dates
- Jul 2004to Mar 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 3 months
- All sexes
- Healthy volunteers accepted
- Child
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
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Emory University
Atlanta, Georgia, 30303
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Wake Forest University
Charlotte, North Carolina, 27157
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
Wayne State University
Detroit, Michigan, 48201
RTI International
Durham, North Carolina, 27705
Duke University
Durham, North Carolina, 27710
University of Miami
Miami, Florida, 33136
Stanford University
Palo Alto, California, 94304
University of Rochester
Rochester, New York, 14642
About this study
Official title: Observational Study of the Immunogenicity of Heptavalent Pneumococcal Conjugate Vaccine in Very-low-birth-weight Infants
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.
Read the 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.
- Conditions
- Pneumococcal Infections, Streptococcus Pneumoniae, Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature
- Keywords
- 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
- Medical subject headings
- Pneumococcal Infections, Premature Birth
What is being measured
The primary outcome is the main question the study is designed to answer.
Serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml
Measured: 4-6 weeks following the third dose of PCV-7
Secondary outcomes (9)
Pneumococcal capsular polysaccharide antibody >=0.15 μg/ml for the other six vaccine serotypes
Measured: 4-6 weeks following the third dose of PCV-7
Pneumococcal capsular polysaccharide antibodies >=1.0 μg/ml for all seven vaccine serotypes
Measured: 4-6 weeks following the third dose of PCV-7
Geometric mean titers of pneumococcal capsular polysaccharide antibody to the seven vaccine serotypes
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 18-22 months corrected age
Levels of antibody >=0.15 μg/ml and >=1.0 μg/ml to Hib polyribosylribitol
Measured: 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
Measured: 4-6 weeks following the third dose of PCV-7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2006 (estimated)
- Study startJul 2004
- Primary completionJul 2007
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pneumococcal InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 368 participants (actual)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- Research network
- Collaborators
- National Center for Research Resources (NCRR), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Ronald N. Goldberg, MD, Principal investigator, Duke UniversityBarbara J. Stoll, MD, Principal investigator, Emory UniversityAbhik Das, PhD, Principal investigator, RTI InternationalKrisa P. Van Meurs, MD, Principal investigator, Stanford UniversityWaldemar A. Carlo, MD, Principal investigator, University of Alabama at BirminghamShahnaz Duara, MD, Principal investigator, University of MiamiCarl T. D'Angio, MD, Principal investigator, University of RochesterPablo J. Sanchez, MD, Principal investigator, University of Texas, Southwestern Medical Center at Dallas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00273325
- Sponsor's protocol ID
- NICHD-NRN-0031
- Other IDs
- UL1RR024128, UL1RR024160, UL1RR024982, UL1RR025008, UL1RR025744, UL1RR025777, M01RR016587, M01RR000030
- Acronym
- PCV-7
- Status last verified
- Mar 2019
- First submitted
- 9 Sep 2005
- Last updated
- 22 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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 pneumococcal conjugate vaccine immunogenicity in very-low-birth-weight, premature infants. Pediatr Infect Dis J. 2010 Jul;29(7):600-6. doi: 10.1097/INF.0b013e3181d264a6.
PubMed 20234331Wynn 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 low birth weight infants. J Perinatol. 2013 Aug;33(8):613-8. doi: 10.1038/jp.2013.5. Epub 2013 Jan 31.
PubMed 23370608Ang 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 Streptococcus pneumoniae in very low-birth-weight infants after administration of heptavalent pneumococcal conjugate vaccine. Arch Pediatr Adolesc Med. 2010 Dec;164(12):1173-5. doi: 10.1001/archpediatrics.2010.233. No abstract available.
PubMed 21135351D'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 influenzae type b protein conjugate vaccines in very low birth weight infants. Pediatr Infect Dis J. 2013 Dec;32(12):1400-2. doi: 10.1097/01.inf.0000437263.04493.7c. No abstract available.
PubMed 24569312
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Study of the Immunogenicity of Heptavalent Pneumococcal Conjugate Vaccine in Very-low-birth-weight Infants
- ClinicalTrials.gov ID
- NCT00273325
- Acronym / sponsor ID
- PCV-7 / NICHD-NRN-0031
- Conditions
- Pneumococcal Infections, Streptococcus Pneumoniae, Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature
- Keywords
- NICHD Neonatal Research Network, Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Prematurity, Pneumococcal Vaccines, Vaccines, Conjugate, Immunogenicity, Vaccine Response
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 368 participants (actual)
- Lead sponsor
- NICHD Neonatal Research NetworkResearch network
- Collaborators
- National Center for Research Resources (NCRR), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Jul 2004
- Primary completion
- Jul 2007 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 9 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 3 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- 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
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- Known immunodeficiency
- HIV exposure
- Parental non-consent
- Primary care pediatrician not willing to participate
- Enrollment in a conflicting trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml
Time frame: 4-6 weeks following the third dose of PCV-7
9 secondary outcomes
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
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
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
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
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
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2019.
- Results publication: PubMed 20234331D'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 pneumococcal conjugate vaccine immunogenicity in very-low-birth-weight, premature infants. Pediatr Infect Dis J. 2010 Jul;29(7):600-6. doi: 10.1097/INF.0b013e3181d264a6.
- Results publication: PubMed 23370608Wynn 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 low birth weight infants. J Perinatol. 2013 Aug;33(8):613-8. doi: 10.1038/jp.2013.5. Epub 2013 Jan 31.
- Results publication: PubMed 21135351Ang 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 Streptococcus pneumoniae in very low-birth-weight infants after administration of heptavalent pneumococcal conjugate vaccine. Arch Pediatr Adolesc Med. 2010 Dec;164(12):1173-5. doi: 10.1001/archpediatrics.2010.233. No abstract available.
- Results publication: PubMed 24569312D'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 influenzae type b protein conjugate vaccines in very low birth weight infants. Pediatr Infect Dis J. 2013 Dec;32(12):1400-2. doi: 10.1097/01.inf.0000437263.04493.7c. No abstract available.
- NICHD Neonatal Research NetworkLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald N. Goldberg, MD principal investigator
Duke University
Barbara J. Stoll, MD principal investigator
Emory University
Abhik Das, PhD principal investigator
RTI International
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pneumococcal Infections and Streptococcus Pneumoniae, run by NICHD Neonatal Research Network at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml (time frame: 4-6 weeks following the third dose of PCV-7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00273325, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2019.