High vs.Standard Dose Influenza Vaccine in Pediatric Solid Organ Transplant (SOT) Recipients

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified March 2026 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Information Provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
Clinicaltrials.gov Identifier
NCT05947071
Other Study ID Numbers:
DAIT RTB-019
First Submitted
February 28, 2023
First Posted
July 16, 2023
Last Update Posted
April 20, 2026
Last Verified
March 2026

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Study design: This is a phase II, multi-center, double-blind, randomized controlled immunogenicity and safety trial comparing two doses of HD-QIV or two doses of SD-QIV in pediatric SOT recipients.

Hypotheses:

1. Pediatric SOT recipients who are 1-23 months out from transplant and are administered two doses of HD-QIV will develop higher Hemagglutination Inhibition (HAI) geometric mean titer (GMT) to influenza antigens compared to pediatric SOT recipients receiving two doses of SD-QIV, with Geometric Mean Titer Ratio (GMR) HD-QIV/SD-QIV greater than 1.0.

2. Administration of HD-QIV in pediatric SOT recipients will be well tolerated and the safety profile will be similar to SD-QIV with regards to solicited local and systemic post-administration reactions.

3. Baseline immunophenotypic markers of exhaustion, immune senescence, and immune activation at the pre-vaccine timepoint will correlate with post-vaccine HAI titers.

Study population: The study plans to enroll a total of approximately 312 pediatric heart, liver, and/or kidney transplant recipients between 1 and 23 months post-transplantation.

Study enrollment: The enrollment period will be over three-years. Participants will be randomized into one of two groups. Group 1 will receive two doses of SD-QIV (0.5 mL; 15μg of each influenza antigen) whereas Group 2 will receive two doses HD-QIV (0.7 mL; 60μg of each influenza antigen).

Influenza surveillance: Active surveillance for influenza-like symptoms will begin when influenza season starts in each site's community, defined in previous trials as identification of at least two positive respiratory tests for influenza, with at least 10% of diagnostic tests positive during two consecutive weeks in the local clinical or research laboratory. Enrollment will continue during influenza season with nasal swabs obtained at all main visits to document the occurrence of influenza virus both prior to and after vaccination. During the influenza season, the study staff will attempt to do a weekly telephone and/or electronic communication with the participants to detect and document any influenza-like illness (ILI) and any specific coronavirus disease of 2019 (COVID-19) like symptoms.

If participants meet ILI criteria and/or any specific coronavirus disease of 2019 (COVID-19) like symptoms (see below), an additional nasal swab will be collected\*.

ILI criteria are met by occurrence of one of the conditions below:

* Fever: ≥38°C (100.4°F)

* Two or more of any of the following: respiratory symptoms (rhinorrhea, sinus congestion, post-nasal drip, shortness of breath, cough, wheezing, sputum production, sore throat, sneezing, watery eyes, ear pain, hoarseness); or systemic symptoms (myalgias, chills, chest pain, or headache); or new loss of taste or new loss of smell; or gastrointestinal symptoms (diarrhea or vomiting).

* Per investigators' discretion at each individual site, a swab is not needed if there is a known non-respiratory cause of symptoms.

Condition or DiseaseIntervention/Treatment
Immunization; InfectionTransplantation InfectionInfluenza
Biological: Standard Dose Quadrivalent Inactivated Influenza VaccineBiological: High Dose Quadrivalent Inactivated Influenza Vaccine

Study Design

Study TypeInterventional
Actual Enrollment312 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposePrevention
Official TitleComparison of High vs Standard Dose Influenza Vaccines in Pediatric Solid Organ Transplant Recipients
Study Start DateSeptember 25, 2024
Actual Primary Completion Date1yr 1mo from now
Actual Study Completion Date1yr 3mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Two Doses Standard Dose Quadrivalent Inactivated Influenza Vaccine
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.
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.

Outcome Measures

Primary Outcome Measures
  1. Immunogenicity: Hemagglutination Inhibition (HAI) titers
    Antibody titers will be measured by hemagglutination inhibition assay.
  2. Safety: solicited local and systemic post-administration reactions
    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. Immunogenicity: Hemagglutination Inhibition (HAI) titers
    Antibody titers will be measured by hemagglutination inhibition assay.
  2. The number of participants achieving seroprotection and seroconversion for influenza virus.
    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.
  3. Durability of immunogenicity
    Measured as Hemagglutination Inhibition (HAI) titer at end of season

Eligibility Criteria

Ages Eligible for Study(Child)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
1. Male or female, 3-17 years of age at time of enrollment 2. Pediatric kidney, heart, and/or liver transplant recipient ≥1 month and \<24 months post-transplant at the time of study immunization
Note: Inclusion of recipients of multiple organs is permitted but is limited to recipients of any combination of organs including kidney, heart and/or liver
Note: Participants undergoing re-transplantation are permitted 3. Anticipated to be available for duration of the study 4. Available by telephone, email, or text message
Exclusion Criteria
1. Inability (i.e. not able to understand and provide consent) or unwillingness of a participant/parent/legal guardian to give written informed consent or comply with study protocol 2. History of severe hypersensitivity to influenza vaccination or anaphylaxis to eggs/egg protein 3. History of severe latex hypersensitivity 4. History of Guillain-Barre syndrome 5. History of lung or intestine transplant 6. HIV positive patients (testing within 24 months of enrollment) 7. Receipt of current season's influenza vaccine post-transplant prior to enrollment in the study 8. Currently pregnant or lactating (females of childbearing age may be enrolled based on self-report, urine pregnancy test must be performed prior to each influenza vaccine) 9. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Contacts and Locations

Sponsors and CollaboratorsNational Institute of Allergy and Infectious Diseases (NIAID)
Locations
Stanford University | Stanford California, United States, 94305Children's Healthcare of Atlanta | Atlanta Georgia, United States, 30322Ann Robert H. Lurie Children's Hospital of Chicago | Chicago Illinois, United States, 60614Children's Mercy Hospital | Kansas City Missouri, United States, 64108Cincinnati Children's Hospital Medical Center | Cincinnati Ohio, United States, 45229UPMC Children's Hospital of Pittsburgh | Pittsburgh Pennsylvania, United States, 15224Monroe Carell Jr. Children's Hospital at Vanderbilt | Nashville Tennessee, United States, 37232Texas Children's Hospital | Houston Texas, United States, 77030