We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Immunogenicity of Fluzone High Dose in Immunocompromised Children and Young Adults

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01685372
First Posted: September 14, 2012
Last Update Posted: November 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Colorado Clinical & Translational Sciences Institute
Information provided by (Responsible Party):
University of Colorado, Denver
  Purpose
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) Dialysis Biological: Fluzone High Dose Biological: Fluzone Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, 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:
  • Number of Episodes of Influenza and Influenza-Like-Illness Reported in High Dose and Standard Dose Vaccination Groups [ Time Frame: up to 10 months after vaccination ]

    Gathered data on influenza and influenza-like-illness during the influenza season for which the subject was vaccinated. Reported numbers of episodes of PCR-diagnosed influenza and rates of reported Influenza-Like-Illness (ILI) from Questionnaire #2 and also that were obtained from medical records. Data were categorized by the following:

    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
    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.]

  • Number of Subjects Seroprotected at Timepoint 2 in High Dose and Standard Dose Vaccination Groups [ Time Frame: blood draw at 10-45 days post-vaccination ]
    Measure hemagglutinin inhibition (HAI) on blood samples #2 for all subjects, which is the sample drawn at the "peak" of the immune response. Compare number of subjects who are seroprotected (reaching HAI ≥ 1:40) between the high-dose and standard-dose recipients..


Secondary Outcome Measures:
  • Number of Adverse Events Definitely or Possibly Related to Vaccination Reported Within 14 Days of Vaccination [ Time Frame: 0-14 days after vaccination ]
    Number of adverse events reported within the 14 days after vaccination by each subject within each patient group. Data collected from that reported in safety questionnaires and in Safety Diary that spanned the 14 days post-vaccination.

  • Number of Subjects With Seroconversion From T1 to T2 in the High Dose and Standard Dose Vaccine Groups [ Time Frame: 10-45 days post-vaccination ]
    HAI was measured on blood samples #1 and #2 for all subjects. Seroconversion is defined as a four-fold increase in antibody level between the high-dose and standard-dose recipients within each patient group was performed.

  • Number of Participants Seroprotected at Timepoint 3 in High Dose and Standard Dose Vaccination Groups [ Time Frame: at least 5 months post vaccination ]
    Measure HAI on blood sample #3, drawn May-September following vaccination. Report number who still have HAI ≥ 1:40 in the high-dose and standard-dose groups.

  • Change in Disease Status From Vaccination Through June of the Following Year [ Time Frame: up to 9 months post-vaccination ]
    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. Subjects considered "worse" had worsening function of transplanted organ or complications related to underlying condition (e.g. dialysis) or new diagnosis of disease considered serious by PI.

  • Number of Adverse Events Considered Definitely or Possibly Related to Vaccination Through Sept 30 of the Year Following Vaccination. [ Time Frame: (1) Date of vaccine through day 30 post-vaccine; (2) Day 31 post-vaccine through September 30 of the year following vaccine ]

    Data gathered from the following

    1. Safety data in 1st 14 days (safety surveys and safety diary)
    2. Safety survey at day 30-45 regarding any unplanned health care visit or other AE during the 30 days after vaccine
    3. On-going passive surveillance of adverse events (AEs)/serious adverse events (SAEs) throughout course of influenza season of enrollment
    4. Chart review of each participant by PI through Sept 30 of the year following vaccine Data collection stopped in September following enrollment.


Other Outcome Measures:
  • Additional Measures of Immunogenicity in High Dose and Standard Dose Vaccinations [ Time Frame: 10-45 days post-vaccination ]
    This secondary objective was included as exploratory and we plan to add additional analyses when funding is secured. There is no anticipated date when we will have this completed. (No immunogenicity studies have been done besides HAI.) For other immunogenicity: would compare results of blood draw #1 and #2 between the high-dose and standard-dose recipients for each patient group for any of the following: antibody avidity, microneutralization, T-cell interferon, T-cell IL-2, B-cell Immunoglobulin G (IgG) and B-cell Immunoglobulin A (IgA).

  • Numbers of Subjects Who Were Both Seroprotected and Who Seroconverted at T2 and T3 After Vaccination [ Time Frame: (1) T2 measured 14-45 days post-vaccination; (2) T3 measured June 1-Sept 30 post-vaccination (end-of season), following vaccination ]
    Seroprotection (HAI>=1:40) and seroconversion (4-fold increase) together have been found to be a better predictor of vaccine effectiveness. Patients had to have both a 4-fold rise in HAI and have HAI>=40 to be counted


Enrollment: 16
Study Start Date: September 2012
Study Completion Date: September 2017
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
A single-dose of high-dose influenza vaccine will be administered to subjects randomized to this arm
Other Names:
  • high-dose influenza vaccine
  • influenza vaccine
Active Comparator: Fluzone
Fluzone 0.5mL IM given once
Biological: Fluzone
A single-dose of standard-dose influenza vaccine will be administered to subjects randomized to this arm
Other Name: influenza vaccine

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   5 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01685372


Locations
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Colorado Clinical & Translational Sciences Institute
Investigators
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
ClinicalTrials.gov Identifier: NCT01685372     History of Changes
Other Study ID Numbers: 12-0829
First Submitted: August 27, 2012
First Posted: September 14, 2012
Results First Submitted: June 30, 2017
Results First Posted: November 30, 2017
Last Update Posted: November 30, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share data at the end of the study. Data management at the close of the study will occur according to IRB and FDA regulations.

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Collagen Diseases
Rheumatic Diseases
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Connective Tissue Diseases
Musculoskeletal Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs