Influenza Vaccine in Premature Infants

NCT ID: NCT00455169

Last Updated: 2015-09-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 66 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2008-05-31

Brief Summary

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.

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.

Conditions

Influenza; Infant, Premature

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

1

Premature infants

Trivalent Inactivated Influenza Vaccine

Intervention Type: BIOLOGICAL

Influenza vaccine

2

Full term infants

Trivalent Inactivated Influenza Vaccine

Intervention Type: BIOLOGICAL

Influenza vaccine

Interventions

Trivalent Inactivated Influenza Vaccine

Influenza vaccine

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

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

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.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 17 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thrasher Research Fund

OTHER

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: collaborator

State University of New York at Buffalo

OTHER

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Carl D'Angio

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carl T D'Angio, MD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

University of Miami

Miami, Florida, United States

State University of New York at Buffalo

Buffalo, New York, United States

University of Rochester

Rochester, New York, United States

Wake Forest University

Winston-Salem, North Carolina, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

References

D'Angio CT, Heyne RJ, Duara S, Holmes LC, O'Shea TM, Wang H, Wang D, Sanchez PJ, Welliver RC, Ryan RM, Schnabel KC, Hall CB; Premature Infant Vaccine Collaborative. Immunogenicity of trivalent influenza vaccine in extremely low-birth-weight, premature versus term infants. Pediatr Infect Dis J. 2011 Jul;30(7):570-4. doi: 10.1097/INF.0b013e31820c1fdf.

Reference Type: DERIVED

PMID: 21273938 (View on PubMed)

Other Identifiers

URRSRB15397A

Identifier Type: -

Identifier Source: org_study_id