Immunogenicity of Fluzone High Dose in Immunocompromised Children and Young Adults

This study is ongoing, but not recruiting participants.
Colorado Clinical & Translational Sciences Institute
Information provided by (Responsible Party):
University of Colorado, Denver Identifier:
First received: August 27, 2012
Last updated: April 20, 2016
Last verified: April 2016
The purpose of this study is to determine whether Fluzone High Dose increases the immune response to the influenza antigens contained in the vaccine compared to standard-dose Fluzone in immunocompromised children and young adults. Safety and efficacy data will also be collected.

Condition Intervention Phase
Solid Organ Transplant Recipient (Liver, Kidney, Heart)
Rheumatologic Disorder
Human Immunodeficiency Virus (HIV)
Bone Marrow Transplant (BMT)
Biological: Fluzone High Dose
Biological: Fluzone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Immunogenicity and Efficacy of High-dose Trivalent Inactivated Seasonal Influenza Vaccine(Fluzone High Dose) in Immunocompromised Children and Young Adults.

Resource links provided by NLM:

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Efficacy [ Time Frame: up to 10 months after vaccination ] [ Designated as safety issue: No ]

    Gathering data on influenza-like-illness during the influenza season for which the subject was vaccinated in the study. Influenza season typically lasts January through May. Compare rates of diagnosed influenza and rates of reported Influenza Like Illness (ILI) from Questionnaire #2 and also obtained from medical records between the high-dose and standard-dose recipients within each patient group for each influenza season included in the study. We will obtain 3 sets of data related to influenza/ILI and analyze combinations of them.

    1. Polymerase chain reaction (PCR)-proven diagnosis of influenza performed at Children's Hospital Colorado (CHC)
    2. Diagnosis of influenza by non-PCR rapid-influenza test (diagnosed outside of main-campus CHC)
    3. Diagnosis of ILI (from questionnaire #2). [Centers for Disease Control (CDC) definition of ILI: Fever ≥ 100°F AND cough or sore throat in the absence of another known cause other than influenza for the illness.]

  • Seroprotection [ Time Frame: blood draw at 10-45 days post-vaccination ] [ Designated as safety issue: No ]
    Measure hemagglutinin inhibition (HAI) on blood samples #1 and #2 for all subjects, which is the sample drawn at the "peak" of the immune response. Compare percentage reaching HAI ≥ 1:32 (or 1:40) between the high-dose and standard-dose recipients within each patient group between timepoint 0 (pre-vaccination) and blood draw #2.

Secondary Outcome Measures:
  • Safety [ Time Frame: 0-14 days after vaccination ] [ Designated as safety issue: Yes ]
    Compare proportion of adverse events reported within the 14 days after vaccination by each subject. Compare types and rates of adverse events between the high-dose and standard-dose recipients within each patient group. Subjects will keep a Safety Diary for the 14 days post-vaccination.

  • Seroconversion [ Time Frame: 10-45 days post-vaccination ] [ Designated as safety issue: No ]
    Measure HAI on blood samples #1 and #2 for all subjects. Compare percentage reaching a four-fold increase in antibody level between the high-dose and standard-dose recipients within each patient group.

  • Other immunogenicity [ Time Frame: 10-45 days post-vaccination ] [ Designated as safety issue: No ]
    For other immunogenicity: Compare results of blood draw #1 and #2 between the high-dose and standard-dose recipients for each patient group for the following: antibody avidity, microneutralization, T-cell interferon, T-cell IL-2, B-cell Immunoglobulin G (IgG) and B-cell Immunoglobulin A (IgA).

  • End of season seroprotection [ Time Frame: at least 5 months post vaccination ] [ Designated as safety issue: No ]
    Measure HAI on blood sample #3, to be drawn May-September following vaccination. Compare percentage who still have HAI ≥ 1:32 (1:40) between the high-dose and standard-dose recipients within each patient group.

  • Change in disease status after vaccination [ Time Frame: up to 6 months post-vaccination ] [ Designated as safety issue: No ]
    Evaluate disease status changes reported by subject on Questionnaire #2 as well as changes reported in clinic notes over the course of the influenza season. Statistical analysis will compare rates of progress or improvement of disease within the 2 months after vaccination and then within 6 months after vaccination between the high-dose and standard-dose recipients within each patient group.

  • Safety [ Time Frame: 12 months after vaccination ] [ Designated as safety issue: Yes ]
    1. Will survey subjects at day 30-45 regarding any unplanned health care visit
    2. Will have on-going passive surveillance of adverse events (AEs)/serious adverse events (SAEs) throughout course of influenza season of enrollment. Data collection will stop in September following enrollment.

Estimated Enrollment: 360
Study Start Date: September 2012
Estimated Study Completion Date: December 2016
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fluzone High Dose
Fluzone High Dose 0.5 mL intramuscularly (IM) given once
Biological: Fluzone High Dose
Other Names:
  • high-dose influenza vaccine
  • influenza vaccine
Active Comparator: Fluzone
Fluzone 0.5mL IM given once
Biological: Fluzone
Other Name: influenza vaccine


Ages Eligible for Study:   5 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age ≥ 5 years and ≤ 35 years
  • Receiving influenza vaccination in Children's Hospital Colorado (CHC) clinic as part of routine clinical care
  • Only supposed to receive one dose of influenza vaccine
  • Rheumatology patients: must be on some type of immunosuppressive or immunomodulatory medication at the time of immunization and considered at least moderately immunosuppressed in the opinion of the primary rheumatologist. Basic guidelines for rheumatology patients: (1) Any patient receiving monoclonal antibody therapy (i.e., infliximab, etanercept, tocilizumab, anakinra) must also be taking another immunosuppressive/immunomodulatory medication; (2) Patients taking steroids as monotherapy must be on a dose of ≥ 2mg/kg/day OR ≥ 20mg/day; (3) Patients on combination therapy where the dose of a single drug may not be very high, but the combination is considered moderately or severely immunosuppressive will be eligible.
  • Bone Marrow Transplant patients: all patients in clinic eligible
  • Oncology patients: must be on some type of chemotherapy
  • Hemodialysis patients: must be on dialysis
  • Child Health Immunodeficiency Program (CHIP) patients: must have a known diagnosis of HIV
  • Solid Organ Transplant patients: post-transplant, influenza vaccine recommended by primary transplant physician

Exclusion Criteria:

  • Rheumatology patients: if receiving any of the monoclonal antibodies, etanercept, infliximab, adalimumab, tocilizumab, atlizumab, or anakinra, must also be taking at least one other immunosuppressive/immunomodulatory medication
  • Unable to come for scheduled follow-up appointments
  • History of anaphylaxis reaction to influenza vaccination in the past
  • Severe allergic reaction to any component of the vaccine, including egg protein, or after previous dose of any influenza vaccine
  • History of Guillain-Barre syndrome ever in the past in the subject or in a parent or a sibling of the subject
  • Allergy to latex
  • Intravenous immuneglobulin (IVIG) within in 4 weeks preceding any blood draw
  • Receiving an investigational agent as part of another study or other medical treatment (investigational = not-FDA approved for any indication)
  • Subject not enrolled in other studies that prohibit him/her from enrolling in this study
  • Blood draw contraindicated
  • Pregnancy
  • Breastfeeding
  • Received a polysaccharide vaccine (pneumovax) w/in 3 weeks of the vaccination
  • Absolute neutrophil count (ANC) < 500/uL at the time of vaccination or could potentially have ANC 500/uL during the 5 days after vaccination
  • Platelet count < 50,000/uL at the time of vaccination
  • If a subject has a temperature ≥ 100.4°F at the time of enrollment, then the subject must choose to not enroll or delay immunization until afebrile.
  • Receiving influenza vaccination past December 15 of influenza season.
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Please refer to this study by its identifier: NCT01685372

United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Colorado Clinical & Translational Sciences Institute
Principal Investigator: Donna Curtis, MD, MPH Children's Hospital Colorado, University of Colorado Denver School of Medicine
  More Information

Responsible Party: University of Colorado, Denver Identifier: NCT01685372     History of Changes
Other Study ID Numbers: 12-0829 
Study First Received: August 27, 2012
Last Updated: April 20, 2016
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Collagen Diseases
Immunologic Deficiency Syndromes
Connective Tissue Diseases
Immune System Diseases
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Immunologic Factors
Physiological Effects of Drugs processed this record on May 26, 2016