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Study of Live, Attenuated Influenza Vaccination in Preterm and Full-Term Infants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Carl D'Angio, University of Rochester
ClinicalTrials.gov Identifier:
NCT01194297
First received: August 31, 2010
Last updated: October 8, 2012
Last verified: October 2012
History of Changes
  Purpose

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. The recently-licensed live attenuated influenza vaccine (LAIV) promotes better immune responses than the trivalent inactivated vaccine, but can cause wheezing. The balance of risks and benefits for LAIV in extremely premature infants, who may be at increased risk for both influenza disease and vaccine side effects, is unknown.

The specific aim of this project is to compare the immune response and reactions of trivalent, inactivated influenza vaccine (TIV) and live, attenuated, intranasal influenza vaccine (LAIV) in groups of former premature (PT), very (V) LBW and former full-term (FT) infants aged 24-35 months.

The investigators hypothesize that the immune response in FT infants will be greater with LAIV than TIV, and that wheezing episodes will be no more than twice as frequent in LAIV as in TIV recipients.

The study will enroll 14 former premature, VLBW infants and 14 former full-term infants. Children will be randomized to receive one dose either TIV or LAIV. Vaccine reactions will be measured. One to two teaspoons mL of blood will be drawn at 0 and 7-14 days from immunization, and less than one teaspoon of blood will be drawn at 28-42 days.


Condition Intervention Phase
Influenza Infection
 Biological: Live attenuated influenza vaccine
Biological: Inactivated influenza vaccine
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Immune Responses in Preterm and Full-Term Infants Following Live, Attenuated Influenza Vaccination

Resource links provided by NLM:

MedlinePlus related topics: Flu
U.S. FDA Resources

Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • Humoral immunogenicity [ Time Frame: 28-42 days ] [ Designated as safety issue: No ]
    Hemagglutinin specific antibody, as measured by hemagglutination inhibition


Secondary Outcome Measures:
  • Medically-attended wheezing [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
    Wheezing that triggers a visit for medical care


Enrollment: 3
Study Start Date: August 2010
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Live attenuated influenza vaccine
One dose of live attenuated influenza vaccine, according to routine immunization recommendations
 Biological: Live attenuated influenza vaccine
One dose of live attenuated influenza vaccine, according to routine immunization recommendations
Other Name: FluMist
Active Comparator: Inactivated influenza vaccine
One dose of inactivated influenza vaccine, according to routine immunization recommendations
 Biological: Inactivated influenza vaccine
One dose of inactivated influenza vaccine, according to routine immunization recommendations
Other Name: Fluzone

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. The recently-licensed live attenuated influenza vaccine (LAIV) is more immunogenic than the trivalent inactivated vaccine, but its use in infants and high risk children is limited by side effects. The risk/benefit ratio of LAIV in extremely premature infants, who may be at increased risk for both influenza disease and vaccine side effects, is unknown.

Aim. The specific aim of this project is to compare the immunogenicity and reactogenicity of trivalent, inactivated influenza vaccine (TIV) and live, attenuated, intranasal influenza vaccine (LAIV) in groups of former premature (PT), very (V) LBW and former full-term (FT) infants aged 24-35 months.

Hypotheses.

  1. The humoral immunogenicity of LAIV, as measured by HI, will be greater than that of TIV. This will be the co-primary outcome for this study.
  2. Vaccine reactogenicity, as measured by medically-attended wheezing episodes, will be no more than twice as frequent in LAIV as in TIV recipients. This will be the co-primary outcome for this study.
  3. Functional B-cell responses, as measured by antibody secreting cell (ASC) ELISPOT, will be greater in LAIV-immunized infants than TIV-immunized infants.
  4. Peak T-cell cytokine responses, as measured by IFNγ, IL-2 and IL-4 ELISPOT, will be greater in LAIV-immunized infants than TIV-immunized infants.
  5. Hemagglutinin-specific nasal IgA will be measureable following LAIV immunization.
  6. Former premature infants will have similar adaptive immune responses, but elevated reactogenicity to both vaccines, when compared to former full-term infants.

Design. The study will enroll 14 former premature, VLBW infants and 14 former full-term infants. Subjects, who will be eligible to receive either TIV or LAIV as part of routine care, will be randomized to receive one dose either TIV or LAIV, according to prevailing recommendations for influenza immunization. Randomization will be stratified by prematurity status. Vaccine reactogenicity will be measured by using parent diaries following immunization and questionnaires at each visit. Five to 10 mL of blood will be drawn at 0 and 7-14 days from immunization for isolation of peripheral blood mononuclear cells (PBMC), and 1 mL of blood will be drawn for serum separation for antibody determination at 0 and 28-42 days. Antibody levels and T- and B-cell responses to vaccine will be measured.

Potential Impact. This study is designed to assess the immunogenicity and reactogenicity of two current influenza vaccines in premature infants. The data will be used to estimate the sample size for a definitive trial in younger premature infants.

  Eligibility

Ages Eligible for Study:   24 Months to 35 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Subjects must meet all relevant criteria (by time of influenza vaccination) to participate.

  1. (a) Former premature (<32 weeks' gestation at birth), VLBW (<1500 grams' birth weight) infant, 24 months, 0 days - 35 months, 31 days of age, OR (b) Former full-term (37-42 weeks' gestation at birth), normal birth weight (>2500 grams' birth weight) infant, 24 months, 0 days - 35 months, 31 days of age.
  2. Influenza immunization in prior season.
  3. Eligible for either influenza immunization (TIV or LAIV).
  4. Parental permission.
  5. 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 in child or in a close household contact.

  2. History of:

    • Recurrent episodes of wheezing,
    • Medically-attended wheezing illness in past year, or
    • Hospitalization for a wheezing illness.
  3. Systemic corticosteroid administration at time of influenza vaccination.
  4. Requiring supplemental oxygen at time of influenza vaccination.
  5. Contraindication to either influenza immunization (e.g. egg allergy, aspirin therapy).
  6. Physician-diagnosed influenza illness in the current influenza season.
  7. 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: NCT01194297

Locations
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Rochester
Investigators
Principal Investigator: Carl T. D'Angio, MD University of Rochester
  More Information

No publications provided

Responsible Party: Carl D'Angio, Associate Professor, University of Rochester
ClinicalTrials.gov Identifier: NCT01194297     History of Changes
Other Study ID Numbers: 25914
Study First Received: August 31, 2010
Last Updated: October 8, 2012
Health Authority: United States: Federal Government

Keywords provided by University of Rochester:
influenza
premature infant
very low birth weight infant
immunization
vaccine

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 June 17, 2013