High vs. Standard Dose Influenza Vaccines in Lung Transplant (Repeater)

NCT ID: NCT07192458

Last Updated: 2025-10-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-17
• Study Completion Date: 2029-12-31

Brief Summary

This will be a follow-up study to the "Comparison of High Dose vs. Standard Dose Influenza Vaccine in Lung Allograft Recipient" study (DMID Protocol Number 22-0014) at Vanderbilt University Medical Center.

Lung transplantation is a life-saving therapy for patients with advanced lung disease, and is also associated with an improvement in quality of life. However, due to the need for life-long immunosuppression to prevent acute cellular rejection and chronic lung allograft dysfunction ("chronic rejection"), lung transplant recipients are at risk for developing major infections. In fact, one-year survival is 85%, with infection being the leading cause of death within the first year post-transplant. We will conduct a follow-up phase II, randomized, double-blind trial to assess the impact of subsequent administration of two doses of HD-IIV compared to two doses of SD-IIV among lung recipients during the early post-transplant period. Demonstration of improved immunogenicity from two doses of HD-IIV over consecutive influenza seasons would provide potential broad benefit in reducing influenza disease and its associated complications in lung transplant recipients. Moreover, studying vaccine immunogenicity and safety in the same participants over consecutive years can provide insight into the influence of immunosuppression levels and allograft aging on vaccine-mediated immune modulation. This proposed study design will contribute significantly to influenza vaccination guidance and policy for the highly vulnerable lung transplant population. This proposed study is designed to address several key knowledge gaps in vaccine-mediated protection of lung transplant recipients against influenza:

• Is there increased immunogenicity with administration of one or two doses of HD-IIV or SD-IIV in the subsequent season compared to two doses of HD-IIV or SD-IIV in the first season?
• What is the durability of the humoral and cellular immune response between influenza seasons and does two doses of HD-IIV or SD-IIV sustain higher HAI titers compared to two doses of HD-IIV or SD-IIV in the first season?
• What is the impact of maintenance immunosuppression levels on influenza vaccine immunogenicity within the same participant?
• Will the optimal immunogenic vaccination strategy be associated with an acceptable long-term safety profile over successive influenza seasons, including injection-site and systemic reactions, allosensitization, and organ rejection?

Detailed Description

The study is a phase II, single-center, double-blind, randomized controlled immunogenicity and safety trial comparing two doses of HD-IIV to two doses of SD-IIV over two consecutive years in lung transplant recipients. At study enrollment, following consent, participants will receive either HD-IIV or SD-IIV , with study arm assignments based on DMID protocol number 22-0014. Therefore, participants will ultimately receive four total doses of either HD-IIV or four total doses of SD-IIV over two consecutive influenza seasons.

Conditions

Immunization; Infection|Transplantation Infection|Influenza; Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Fluzone: Two Doses High Dose Inactivated Influenza Vaccine

Fluzone: Two Doses of HD-IIV

Group Type: EXPERIMENTAL

Fluzone High Dose Inactivated Influenza Vaccine

Intervention Type: BIOLOGICAL

Fluzone High-Dose (Influenza Vaccine) for intramuscular use 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 containing hemagglutinin (HA) antigen is further purified and then suspended in sodium phosphate-buffered isotonic sodium chloride solution. The Fluzone High-Dose process uses an additional concentration factor after the ultrafiltration step to obtain a higher HA antigen concentration. The purified split virus from the three strains included in the vaccine are produced separately and then combined to make the trivalent formulation.

Fluzone: Two Doses Standard Dose Inactivated Influenza Vaccine

Fluzone: Two Doses of of SD-IIV

Group Type: EXPERIMENTAL

Fluzone Standard Dose Inactivated Influenza Vaccine

Intervention Type: BIOLOGICAL

Fluzone Standard Dose is a vaccine indicated for active immunization for the prevention of disease caused by influenza A subtype viruses and type B virus contained in the vaccine.

Interventions

Fluzone High Dose Inactivated Influenza Vaccine

Fluzone High-Dose (Influenza Vaccine) for intramuscular use 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 containing hemagglutinin (HA) antigen is further purified and then suspended in sodium phosphate-buffered isotonic sodium chloride solution. The Fluzone High-Dose process uses an additional concentration factor after the ultrafiltration step to obtain a higher HA antigen concentration. The purified split virus from the three strains included in the vaccine are produced separately and then combined to make the trivalent formulation.

Intervention Type: BIOLOGICAL

Fluzone Standard Dose Inactivated Influenza Vaccine

Fluzone Standard Dose is a vaccine indicated for active immunization for the prevention of disease caused by influenza A subtype viruses and type B virus contained in the vaccine.

Intervention Type: BIOLOGICAL

Other Intervention Names

Fluzone High Dose; Fluzone

Eligibility Criteria

Inclusion Criteria

• Lung transplant recipient who enrolled and completed Visits 1, 2, and 3 of the DMID protocol number 22-0014 during the prior 2024-2025 or 2025-2026 influenza season, respectively

• Anticipated to be available for the duration of the study
• Can be reached by telephone, text message, email, or electronic health record messaging

Exclusion Criteria

• Recipient of multi-organ, extra-pulmonary, and/or hematopoietic stem cell transplant
• Recipient of a re-do lung transplant
• History of Guillain-Barre syndrome
• History of receiving the current season's influenza vaccine prior to study enrollment and/or Visit 1 of this follow-up study
• Pregnant person
• Laboratory-confirmed influenza disease after September 1st in the current influenza season and before enrollment in this follow-up study (patient can still receive the second influenza vaccination despite proven influenza disease after enrollment)
• CMVIG/IVIG/SCIG receipt within 28 days of each vaccine
• Receipt of rituximab or other B-cell depleting antibody (including proteasome inhibitors) therapy within 3 months of 1st vaccine dose (Day 0)
• Receipt of T-cell depleting therapies (anti-thymocyte globulin, alemtuzumab, daratumumab) between the completion of Visit 3 of the initial study and enrollment in this follow-up study
• Investigator concern about study participation
• Note: Criteria for temporarily delaying vaccine administration: The following conditions are temporary or self-limiting, and a participant may be included in the study once the condition has resolved, provided that the participant is otherwise eligible:

• Fever ≥100.4ºF/38.0ºC (oral measurement), or an acute severe illness within 48 hours of enrollment
• Receipt of any live vaccines within four weeks or any inactivated vaccines within two weeks prior to potential study vaccination

No children have been enrolled in the DMID protocol number 22-0014; therefore, only adults will be enrolled in this current study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Natasha Halasa

Professor of Pediatric Infectious Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Natahsa Halasa, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Natahsa Halasa, MD, MPH

Role: CONTACT

natasha.halasa@vumc.org

615-322-2250

Shari D. Barto

Role: CONTACT

shari.barto@vumc.org

615-421-0942

Facility Contacts

Natahsa Halasa, MD, MPH

Role: primary

natasha.halasa@vumc.org

6153223346

Shari D. Barto

Role: backup

shari.barto@vumc.org

615-421-0942

Other Identifiers

251037

Identifier Type: -

Identifier Source: org_study_id