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High vs. Standard Dose Influenza Vaccine in Lung Allograft Recipients

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ClinicalTrials.gov Identifier: NCT05215327
Recruitment Status : Recruiting
First Posted : January 31, 2022
Last Update Posted : November 23, 2022
Sponsor:
Collaborators:
Northwestern University Feinberg School of Medicine
University of Alabama at Birmingham
University of Washington
Duke University
Information provided by (Responsible Party):
Natasha Halasa, Vanderbilt University Medical Center

Brief Summary:

Lung allograft recipients have a higher burden of influenza disease and greater associated morbidity and mortality compared with healthy controls. Induction and early maintenance immunosuppression is thought to impair immunogenicity to standard dose inactivated influenza vaccine. This early post-transplant period is when immunity is most desirable, since influenza disease during this time frame is associated with adverse consequences. Thus, strategies to reduce severe influenza disease in this highly susceptible population are critical. No trials in lung transplant recipients have evaluated two doses of HD-IIV within the same influenza season as a strategy to improve immunogenicity and durability of influenza prevention. Furthermore, no influenza vaccine trials have focused on enrollment of subjects at early post-transplant timepoints. Very few studies have been performed in solely lung allograft recipients. Immunosuppression intensity is highest in lung patients, thereby limiting comparisons to recipients of heart, liver, and kidney transplants. Therefore, studies to assess both HD-IIV and two-dose strategies in the same influenza season in post-lung transplant recipients are greatly needed.

The central hypothesis of our proposal is that lung allograft recipients who are 1-35 months post-transplant and receiving two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have higher HAI geometric mean titers (GMT) to influenza antigens compared to those receiving two doses of SD-QIV. To test this hypothesis and address the above critical knowledge gaps, we propose to conduct a phase II, multi-center, randomized, double-blind, controlled immunogenicity and safety trial comparing the administration of two doses of HD-QIV to two doses of SD-QIV in lung allograft recipients 1-35 months post-transplant. The results of this clinical trial will address significant knowledge gaps regarding influenza vaccine strategies (e.g., one vs. two doses and HD-QIV vs. SD-QIV) and immune responses in lung transplant recipients and will guide vaccine recommendations during the post-transplant period.


Condition or disease Intervention/treatment Phase
Immunization; Infection Transplantation Infection Influenza Biological: High Dose Quadrivalent Inactivated Influenza Vaccine Biological: Standard Dose Quadrivalent Inactivated Influenza Vaccine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The primary goal of this study is to compare influenza vaccine immunogenicity and safety between two doses of HD-QIV and two doses of SD-QIV in a population of lung transplant recipients. The study will be powered on a comparison of the primary immunogenicity outcome. A nominal level of α = 0.05 (two-sided) will be used to determine statistical significance
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: All study staff, and subjects will be blinded to which vaccine the subject will receive, except for an un-blinded vaccinator. This individual will not inform the study team or the subjects which vaccine they administered to the subject. The un-blinded vaccinator will not participate in any other study activities. If the study vaccine is provided in a blinded manner, then research staff will be able to administer the vaccine, and an un-blinded vaccinator will not be necessary. The pharmacy will be un-blinded and will have a record of which vaccine was given to each subject.
Primary Purpose: Prevention
Official Title: Comparison of High Dose vs. Standard Dose Influenza Vaccines in Lung Allograft Recipients
Actual Study Start Date : November 7, 2022
Estimated Primary Completion Date : July 2027
Estimated Study Completion Date : December 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot Vaccines

Arm Intervention/treatment
Experimental: Two Doses High Dose Quadrivalent Inactivated Influenza Vaccine
two doses of HD-QIV (0.7 mL; 60µg of each influenza antigen) 28-42 days apart
Biological: High Dose Quadrivalent Inactivated Influenza Vaccine
Fluzone High-Dose (Influenza Vaccine) for intramuscular injection is an inactivated influenza vaccine, prepared from influenza viruses propagated in embryonated chicken eggs. The virus-containing allantoic fluid is harvested and inactivated with formaldehyde. Influenza virus is concentrated and purified in a linear sucrose density gradient solution using a continuous flow centrifuge. The virus is then chemically disrupted using a non-ionic surfactant, octylphenol ethoxylate (Triton® X-100), producing a "split virus". The split virus is further purified and then suspended in sodium phosphatebuffered isotonic sodium chloride solution. The Fluzone High-Dose process uses an additional concentration factor after the ultrafiltration step in order to obtain a higher hemagglutinin (HA) antigen concentration.
Other Name: Fluzone High Dose

Experimental: Two Doses Standard Dose Quadrivalent Inactivated Influenza Vaccine
receive two doses of SD-QIV (0.5 mL; 15µg of each influenza antigen) 28-42 days apart
Biological: Standard Dose Quadrivalent Inactivated Influenza Vaccine
Fluzone ® Quadrivalent is a vaccine indicated for active immunization for the prevention of influenza disease caused by two influenza A subtype viruses and two type B viruses contained in the vaccine.
Other Name: Fluzone




Primary Outcome Measures :
  1. Geometric Mean Titers of influenza vaccine antibodies. [ Time Frame: Day 56 (post-vaccination) ]
    Antibody titers will be measured by hemagglutination inhibition assay.

  2. The number of participants reporting solicited injection site reactions and systemic reactions. [ Time Frame: Within 7 days post-vaccination ]
    Post-vaccination local adverse events (pain, tenderness, swelling/induration, erythema/redness, swelling/induration size, and erythema/redness size) and systemic adverse events (Fatigue/malaise, headache, nausea, body ache/myalgia (not at the injection site), general activity level, vomiting, and fever).


Secondary Outcome Measures :
  1. Geometric Mean Titers Ratio of influenza vaccine antibodies (post-/pre-vaccination). [ Time Frame: Day 56 (post-vaccination) ]
    Antibody titers will be measured by hemagglutination inhibition assay.

  2. The number of participants achieving seroprotection and seroconversion for influenza virus. [ Time Frame: Day 56 (post-vaccination) ]
    Antibody titers will be measured by hemagglutination inhibition assay. Seroconversion is defined as ≥ 4-fold rise in hemagglutination inhibition assay titers. Seroprotection is defined as ≥1:40 hemagglutination inhibition assay titer.



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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Lung allograft recipients
  2. Age ≥16 years at time of enrollment
  3. ≥1 month (30 days) and <36 months post-lung transplant
  4. Anticipated to be available for duration of the study
  5. Can be reached by telephone, email, or text message

Exclusion Criteria:

  1. Recipient of multi-organ, extra-pulmonary, and/or hematopoietic stem cell transplant
  2. Recipient of a re-do lung transplant
  3. History of severe hypersensitivity to previous influenza vaccination or anaphylaxis to eggs/egg protein
  4. History of Guillain-Barre syndrome
  5. HIV positive patients, by history or documentation from previous test
  6. History of known severe latex hypersensitivity
  7. History of receiving the current season's influenza vaccine post-transplant prior to enrollment in the study
  8. Pregnant female
  9. Proven influenza disease after September 1st and before first study vaccine (patient can still receive the second influenza vaccination despite proven influenza disease once enrolled)
  10. CMVIG/IVIG/SCIG receipt within 28 days of each vaccine
  11. Receipt of rituximab or other B-cell depleting antibody (including proteasome inhibitors) therapy within 3-months of 1st study vaccine (Day 0).
  12. Receipt of augmented T-cell depleting therapy within 3-months of 1st study vaccine (Day 0)
  13. Investigator concern about study participation

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): NCT05215327


Contacts
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Contact: Natasha Halasa, MD, MPH 615-322-2250 natasha.halasa@vumc.org
Contact: Laura Stewart, PhD 615-343-0218 laura.s.stewart@vumc.org

Locations
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United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Natasha Halasa, MD, MPH    615-322-2250    natasha.halasa@vumc.org   
Principal Investigator: Natasha Halasa, MD         
Principal Investigator: Anil Trindade, MD         
Sponsors and Collaborators
Vanderbilt University Medical Center
Northwestern University Feinberg School of Medicine
University of Alabama at Birmingham
University of Washington
Duke University
Investigators
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Principal Investigator: Natasha Halasa, MD. MPH Vanderbilt University Medical Center
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Responsible Party: Natasha Halasa, Professor of Pediatric Infectious Diseases, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT05215327    
Other Study ID Numbers: 212201
First Posted: January 31, 2022    Key Record Dates
Last Update Posted: November 23, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Natasha Halasa, Vanderbilt University Medical Center:
Influenza
Vaccination
Immunization
Lung Transplantation
High Dose
Fluzone
Standard Dose
Influenza, Human
Communicable Diseases
Additional relevant MeSH terms:
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Influenza, Human
Infections
Communicable Diseases
Disease Attributes
Pathologic Processes
Respiratory Tract Infections
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs