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High vs. Standard Dose Influenza Vaccine in Adult SOT Recipients

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ClinicalTrials.gov Identifier: NCT04613206
Recruitment Status : Not yet recruiting
First Posted : November 3, 2020
Last Update Posted : November 20, 2020
Sponsor:
Collaborators:
Feinberg School of Medicine, Northwestern University
University of Alabama at Birmingham
University of Washington
Information provided by (Responsible Party):
Natasha Halasa, Vanderbilt University Medical Center

Brief Summary:
The influenza virus is a significant cause of morbidity in adult solid organ transplant (SOT) recipients. However, these individuals show a suboptimal response to vaccines including the standard-dose (SD) inactivated influenza vaccine (IIV). Recent studies have investigated two strategies to overcome poor immune responses in SOT recipients: (1) administration of high-dose (HD)-IIV compared to SD-IIV and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza season. The first study compared HD-IIV vs. SD-IIV in adult SOT and noted HD-IIV was safe and reported higher immunogenicity; however, the median post-transplant period was 38 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV a month apart compared to one-dose SD-IIV revealed increased immunogenicity, with a median post-transplantation period of 18 months. Therefore, these studies lack evaluation in the early post-transplantation period in this vulnerable population when influenza disease is most severe. The administration of two-doses of HD-IIV in the same influenza season has also not been studied in SOT recipients. Moreover, the vast majority of SOT influenza vaccinations studies have not substantively evaluated prolonged immunogenicity. Thus, the optimal immunization strategy for SOT recipients less than 12 months post-transplant is poorly-defined. In addition, the immunologic predictors and correlates of influenza vaccine immunogenicity in SOT recipients have not been defined. The investigators hypothesize that adult solid organ transplant recipients that are 1-11 months out from transplant and are receiving high-dose inactivated influenza vaccine will have higher hemagglutination inhibition (HAI) geometric mean titers to influenza A antigens compared to adult SOT recipients receiving standard-dose inactivated influenza vaccine. To test this hypothesis and address the above critical knowledge gaps, The investigators propose to conduct a phase II multicenter randomized controlled trial comparing either two doses HD-IIV, two doses of SD-IIV, or one-dose of HD-IIV in adult kidney, heart, and liver SOT recipients 1-11 months post-transplantation. The results of this study will address significant gaps in knowledge regarding influenza vaccine strategies and immune responses in adult SOT recipients and will guide vaccine recommendations in this vulnerable population.

Condition or disease Intervention/treatment Phase
Immunization; Infection Transplantation Infection Influenza Solid Organ Transplant 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 : 396 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Comparison of High vs. Standard Dose Influenza Vaccines in Adult Solid Organ Transplant Recipients
Estimated Study Start Date : December 15, 2020
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : April 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: Two Doses High Dose Quadrivalent Inactivated Influenza Vaccine
two doses of 0.7 mL HD-IIV (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
two doses of 0.5 mL SD-IIV (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

Experimental: One Dose High Dose Quadrivalent Inactivated Influenza Vaccine
one dose of 0.7 mL HD-IIV (60µg of each influenza antigen) followed by placebo 28-42 days later
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




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

Inclusion criteria

  1. Adult SOT recipients who have undergone kidney, heart, and/or liver transplantation I. Multiple organ recipients are permitted (i.e. any combination of organs including kidney, heart and/or liver).

    II. Subjects undergoing re-transplantation are permitted

  2. Age ≥18 years at vaccination
  3. ≥1 month and <12 months post-SOT
  4. Anticipated to be available for duration of study
  5. Can be reached by telephone, email, or text message

Exclusion criteria

  1. History of severe hypersensitivity to previous influenza vaccination or anaphylaxis to eggs/egg protein
  2. History of Guillain-Barre syndrome
  3. History of known active infection with HIV
  4. History of known severe latex hypersensitivity
  5. History of receiving the current season's influenza vaccine post-transplant prior to enrollment in the study
  6. Pregnant female
  7. 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)
  8. History of lung or intestine transplant
  9. CMVIG/IVIG/SCIG receipt in the 28 days prior to or planned administration within 84-126 days of the calendar date of first vaccination
  10. Subjects must have a platelet count of <20,000 to receive the immunizations

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): NCT04613206


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

Sponsors and Collaborators
Vanderbilt University Medical Center
Feinberg School of Medicine, Northwestern University
University of Alabama at Birmingham
University of Washington
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Responsible Party: Natasha Halasa, Principal Investigator, Professor of Pediatric Infectious Diseases, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT04613206    
Other Study ID Numbers: 12345
First Posted: November 3, 2020    Key Record Dates
Last Update Posted: November 20, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Solid Organ Transplant
Immunization
High Dose
Fluzone
Standard Dose
Additional relevant MeSH terms:
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Influenza, Human
Infection
Communicable Diseases
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs