Influenza Vaccine in Premature Infants

This study has been completed.
Sponsor:
Collaborators:
Thrasher Research Fund
University of Miami
Wake Forest School of Medicine
State University of New York at Buffalo
University of Texas Southwestern Medical Center
Information provided by:
University of Rochester
ClinicalTrials.gov Identifier:
NCT00455169
First received: March 30, 2007
Last updated: July 22, 2009
Last verified: July 2009
  Purpose

Background. Influenza is increasingly recognized as causing severe respiratory illness in children. High-risk infants, like former premature infants, and particularly those with lung disease, have influenza hospitalization rates about five times higher than healthy children. Influenza vaccine does not protect young children against influenza as well as it does healthy adults. A small study that measured antibodies (proteins that protect against infection) to influenza suggested that premature infants get even less protection from influenza vaccine than full-term infants. More information about influenza vaccine in premature infants is needed. The overall goals of this project are to collect information about the how well the influenza vaccine induces antibody production, and to develop the collaborative network of centers necessary for a larger trial of influenza vaccine in premature infants.

Objective and Hypotheses. The objective of this study is to measure the amount of protective antibody produced by influenza vaccine in premature (less than 30 weeks' [about 7 months] gestation at birth), extremely-low-birth-weight (1000 grams [2¼ pounds] or less at birth) infants. Influenza vaccine needs to be given yearly. We will assess premature infants during their first series of influenza vaccines. We hypothesize that the levels of antibody will be lower in premature infants receiving their first series of influenza vaccine than in full-term infants.

Design. We will measure the immune response in premature and full term infants. During the 2007-2008 influenza season, a total of 92 subjects, divided among 2 groups (premature infants 6-17 months old receiving their first influenza vaccine series and full-term infants 6-17 months old receiving their first influenza vaccine series) will be recruited at a consortium of five centers (the University of Rochester, the University of Texas Southwestern Medical Center, Wake Forest University, the University of Miami and the State University of New York at Buffalo), receive 2 doses of influenza vaccine, and have antibody and immune cell responses to each vaccine component measured 4-6 weeks after the second dose of vaccine.

Potential Impact. If this study and future investigations suggested ways to improve premature infants influenza vaccine responses, they could lead to changes in recommendations for the number or timing of vaccine doses or of the type of vaccine used in this high-risk group.


Condition Intervention Phase
Influenza
Infant, Premature
Biological: Trivalent Inactivated Influenza Vaccine
Phase 4

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Influenza Vaccine Immunogenicity in Extremely Premature Infants

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Biospecimen Retention:   None Retained

No retention


Enrollment: 66
Study Start Date: October 2007
Study Completion Date: May 2008
Groups/Cohorts Assigned Interventions
1
Premature infants
Biological: Trivalent Inactivated Influenza Vaccine
Influenza vaccine
2
Full term infants
Biological: Trivalent Inactivated Influenza Vaccine
Influenza vaccine

Detailed Description:

Background. Influenza infection causes an estimated 1 million deaths worldwide yearly. Severe influenza respiratory disease is increasingly recognized in children. Influenza hospitalization rates in high-risk infants, such as premature infants, are increased some five-fold over rates in other children. Influenza vaccine immunogenicity is generally modest even in healthy children, and influenza vaccines have been incompletely studied in premature infants. Further investigation is required to optimize vaccine responses in premature infants. The overall goals of this project are to generate estimates of effect size and variance of influenza vaccine immunogenicity for use in planning a larger multi-center trial, and to develop the collaborative network of centers necessary for such a trial.

Objective and Hypotheses. The primary objective of this study is to measure influenza vaccine immunogenicity in extremely-low-birth-weight (ELBW, < 1001 grams at birth), premature (< 30 weeks' gestation) infants receiving trivalent, inactivated, split-virion influenza vaccine (TIV). We hypothesize that the geometric mean titer (GMT) of antibody to each of the three vaccine components will be lower in ELBW infants receiving their first series of TIV than in full-term (FT, >37 weeks' gestation), normal-birth-weight (>2500 grams) infants.

Specific Aim. To measure the humoral and cellular immunogenicity of influenza vaccine in extremely-low-birth-weight (ELBW, greater than or equal to 1000 grams at birth), premature infants receiving trivalent, inactivated, split-virion influenza vaccine (TIV) for their first influenza vaccine series in 2007-8.

Design. This prospective, cohort, immunogenicity study will estimate the GMT to influenza in ELBW infants, with a comparison group of FT infants. Using the established vaccine study infrastructure at a consortium of five centers (the University of Rochester, the University of Texas Southwestern Medical Center, Wake Forest University, the University of Miami and the State University of New York at Buffalo), we will recruit 46 un-immunized (for influenza) ELBW infants, 6-17 months old and 46 un-immunized FT infants, 6-17 months old. Infants will receive the recommended 2 doses of TIV, 4 weeks apart, with blood drawing at the first vaccine dose and 4-6 weeks after the second. Antibody to each vaccine component will be measured by hemagglutination inhibition. The frequency of hemagglutinin-specific T cell interleukin (IL)-2, IL-4 and interferon gamma (IFNγ) responses will be measured by ELISPOT assay. The primary outcome will be influenza GMT. A sample size of 46 subjects per group provides 80% power, using a two-sided alpha = 0.05, to detect a 1.5-fold difference in GMT between groups, assuming a standard deviation (SD) spanning 0.5 to 2.0 times the value of each GMT. In addition, the five-center consortium will monitor the quality of the collaboration, strengthen its capabilities through the design and implementation of a secure, web-based information system, and expand its efforts by seeking additional, outside funding to implement a companion protocol assessing live attenuated influenza vaccine in premature infants.

Potential Impact. This study is designed to assess the immunogenicity of the current generation of influenza vaccines in premature infants. This and future trials assessing novel immunization strategies (such as an additional vaccine dose) or vaccines (for instance, the live attenuated influenza virus vaccine) in premature infants could eventually lead to the tailoring of specific vaccine strategies for this high-risk group. In addition, this proposal would bring to maturity a multi-center, collaborative mechanism for vaccine trials in premature infants.

  Eligibility

Ages Eligible for Study:   6 Months to 17 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Premature infants < 30 week's gestation, < 1001 grams' birth weight or full-term infants 37-42 week's gestation >2500 grams' birth weight

Criteria

Inclusion criteria. Subjects must meet all relevant criteria to participate.

  1. (a) Former premature (< 30 weeks' gestation at birth), ELBW (<1001 grams' birth weight) infant, 6 months, 0 days - 17 months, 31 days of age., OR (b) Former full term (37-42 weeks' gestation at birth), normal birth weight (>2500 grams' birth weight) infant, 6 months, 0 days - 17 months, 31 days of age.
  2. No prior influenza immunization.
  3. Eligible for influenza immunization.
  4. Parental permission.
  5. Agreement of primary care provider.
  6. Parents likely to be able to comply with study visits.

Exclusion criteria. Subjects may not participate if they meet any one of these criteria.

  1. Known immunodeficiency.
  2. Systemic corticosteroid administration at time of study enrollment.
  3. Requiring supplemental oxygen.
  4. Contraindication to influenza immunization (e.g. egg allergy).
  5. Physician-diagnosed influenza illness in the current influenza season.
  6. Any condition determined by investigator as likely to interfere with evaluation of the vaccine or be a significant potential health risk to the subject.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00455169

Locations
United States, Florida
University of Miami
Miami, Florida, United States, 33101
United States, New York
State University of New York at Buffalo
Buffalo, New York, United States, 14222
University of Rochester
Rochester, New York, United States, 14534
United States, North Carolina
Wake Forest University
Winston-Salem, North Carolina, United States, 27157
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Rochester
Thrasher Research Fund
University of Miami
Wake Forest School of Medicine
State University of New York at Buffalo
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Carl T D'Angio, MD University of Rochester
  More Information

No publications provided by University of Rochester

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Carl D'Angio, University of Rochester
ClinicalTrials.gov Identifier: NCT00455169     History of Changes
Other Study ID Numbers: URRSRB15397A
Study First Received: March 30, 2007
Last Updated: July 22, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by University of Rochester:
Influenza
Infant, Premature
Immunization
Vaccination

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 17, 2014