High vs Standard Dose Flu Vaccine for Lung Transplant Recipients

Overseen By Natasha Halasa, MD, MPH

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Must not be taking: B-cell depleting, T-cell depleting

Disqualifiers: Multi-organ transplant, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

270 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different flu vaccine doses to determine which works better for individuals who have had a lung transplant. It targets those who received their transplant 1 to 35 months ago and are still adjusting to their new lung. Participants will receive either a high-dose flu shot (High Dose Quadrivalent Inactivated Influenza Vaccine) or a standard-dose flu shot to assess which one boosts immunity more effectively. Individuals who have had a lung transplant and have not yet received this season's flu vaccine might be suitable for this study. The goal is to find the best way to protect lung transplant patients from the flu. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have received certain treatments like rituximab or other B-cell depleting therapies within 3 months before the first study vaccine, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both high-dose and standard-dose flu vaccines are generally safe for individuals who have undergone lung transplants. In previous studies, the high-dose vaccine proved safe and enhanced the immune response more effectively than the standard dose, helping the body recognize and combat the flu.

The standard-dose vaccine is also safe and typically well-tolerated. Both vaccines are used in organ transplant recipients and have similar safety profiles. Some individuals might experience mild side effects, such as soreness at the injection site, a slight fever, or fatigue, but serious side effects are rare.

These findings are based on earlier research with transplant patients, though not specifically lung transplant patients during the same period as the current study. Overall, these vaccines are considered safe options for transplant recipients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore different dosing strategies for flu vaccines in lung transplant recipients, a group that faces unique challenges. Unlike the standard flu vaccine doses typically given to the general population, these treatments compare high-dose and standard-dose quadrivalent inactivated influenza vaccines. The high-dose vaccine delivers a larger amount of each influenza antigen (60µg) compared to the standard dose (15µg), which could potentially offer stronger protection for individuals with compromised immune systems post-transplant. This exploration aims to determine if a higher dose could boost immune response and provide better protection against the flu in this vulnerable group.

What evidence suggests that this trial's treatments could be effective for lung transplant recipients?

Research has shown that high-dose flu vaccines can protect lung transplant patients better than regular doses. In this trial, participants will receive either two doses of the High Dose Quadrivalent Inactivated Influenza Vaccine or two doses of the Standard Dose Quadrivalent Inactivated Influenza Vaccine. One study found that high-dose vaccines helped the immune system respond more effectively to the flu virus. Another study showed that high-dose vaccines were about 23.3% to 33.2% more effective than standard doses. Both types of vaccines are safe, but the high-dose version might better prevent the flu in lung transplant patients. This is crucial because these patients are more likely to experience serious flu complications. ^{1 2 4 6 7}

Who Is on the Research Team?

Natasha Halasa, MD, MPH

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for lung transplant recipients aged 16 or older, who are between 1-35 months post-transplant. Participants must be reachable and available throughout the study. Exclusions include re-do transplants, multi-organ transplants, HIV positive individuals, severe latex allergy sufferers, recent recipients of certain immune therapies, pregnant women, those with egg allergies or a history of Guillain-Barre syndrome.

Inclusion Criteria

People who have had a lung transplant

I had a lung transplant between 1 and 36 months ago.

I am 16 years old or older.

Exclusion Criteria

I had the flu after September 1st but before getting the study vaccine.

I have had Guillain-Barre syndrome in the past.

I haven't received T-cell depleting therapy in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two doses of either HD-QIV or SD-QIV 28-42 days apart

8 weeks

2 visits (in-person)

Influenza Surveillance

Active surveillance for influenza-like symptoms during the influenza season

Influenza season

Weekly telephone/electronic communication

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• High Dose Quadrivalent Inactivated Influenza Vaccine
• Standard Dose Quadrivalent Inactivated Influenza Vaccine

Trial Overview The trial tests whether two doses of a High Dose (HD) influenza vaccine provide better protection than two doses of a Standard Dose (SD) vaccine in lung transplant patients. It's designed to see if higher antibody levels against flu result from the HD vaccine in these immunocompromised individuals.

How Is the Trial Designed?

Group I: Two Doses Standard Dose Quadrivalent Inactivated Influenza Vaccine Experimental Treatment 1 Intervention

receive two doses of SD-QIV (0.5 mL; 15µg of each influenza antigen) 28-42 days apart

Group II: Two Doses High Dose Quadrivalent Inactivated Influenza Vaccine Experimental Treatment 1 Intervention

two doses of HD-QIV (0.7 mL; 60µg of each influenza antigen) 28-42 days apart

High Dose Quadrivalent Inactivated Influenza Vaccine is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Fluzone High-Dose for:

• Influenza prevention in individuals 65 years and older

Approved in Canada as Fluzone High-Dose for:

• Influenza prevention in individuals 65 years and older

Approved in European Union as Fluzone High-Dose for:

• Influenza prevention in individuals 65 years and older

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Feinberg School of Medicine, Northwestern University

Collaborator

Trials

34

Recruited

12,300+

Northwestern University Feinberg School of Medicine

Collaborator

Trials

42

Recruited

15,500+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

NYU Langone Health

Collaborator

Trials

1,431

Recruited

838,000+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

Inhaled corticosteroids, such as beclometasone dipropionate, budesonide, and fluticasone propionate, are effective for asthma treatment, showing a dose-response relationship where most benefits are achieved with low to moderate doses, especially in mild-to-moderate cases.

While high doses of fluticasone can provide slight improvements in asthma control, they also significantly increase the risk of oral side effects, highlighting the importance of balancing efficacy and safety in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dose-response characteristics of inhaled corticosteroids when used to treat asthma: an overview of Cochrane systematic reviews. Adams, NP., Jones, PW.[2022]

The study involving 661 children aged 6 months to under 18 years demonstrated that the high-dose quadrivalent influenza vaccine (IIV4-HD) is safe, with no serious adverse events reported and similar rates of mild reactions compared to the standard-dose vaccine.

IIV4-HD at a dose of 60 µg significantly improved immune responses, particularly in younger children (6 months to <3 years), showing higher antibody titers against various influenza strains compared to the standard-dose vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through Chang, LJ., Anderson, EJ., Jeanfreau, R., et al.[2021]

In a study involving 2100 adults aged 60 and older, the high-dose quadrivalent influenza vaccine (IIV4-HD) administered intramuscularly showed superior immune responses compared to the standard-dose vaccine (IIV4-SD) given subcutaneously, indicating better protection against influenza.

Both vaccines had similar safety profiles, with IIV4-HD being well tolerated and no significant safety concerns identified, suggesting it is a safe option for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superior immunogenicity of high-dose quadrivalent inactivated influenza vaccine versus Standard-Dose vaccine in Japanese Adults ≥ 60 years of age: Results from a phase III, randomized clinical trial. Sanchez, L., Nakama, T., Nagai, H., et al.[2023]

The high-dose influenza vaccine (QIV-HD) demonstrated significantly higher immune responses compared to the standard-dose vaccine (QIV-SD) in older adults, with greater geometric mean titers for all four influenza strains tested.

Both QIV-HD and QIV-SD had similar safety profiles, indicating that the high-dose vaccine is not only more effective but also safe for use in individuals aged 65 and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of high-dose quadrivalent influenza vaccine in older adults in Taiwan: A phase III, randomized, multi-center study. Chen, JY., Hsieh, SM., Hwang, SJ., et al.[2023]

The high-dose inactivated influenza vaccine quadrivalent (HD-IIV4) has been shown to be safe and effective in preventing influenza in adults aged 65 and older, with improved immunogenicity against additional B strains compared to standard vaccines.

Despite some increased adverse reactions like injection-site pain and myalgia, HD-IIV4 is recommended as the vaccine of choice for older adults due to its superior efficacy compared to other influenza vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Inactivated Influenza Vaccine Quadrivalent for Older Adults. Chahine, EB.[2021]

In a study involving 2670 healthy adults aged 65 and older, the quadrivalent high-dose influenza vaccine (IIV4-HD) demonstrated non-inferior immunogenicity compared to the licensed trivalent high-dose vaccine (IIV3-HD) for all four influenza strains.

IIV4-HD showed superior immune responses for both B strains compared to IIV3-HD that did not contain the same B-lineage strain, while maintaining a similar safety profile, indicating it is a more effective option without added safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: A phase 3 randomized clinical trial. Chang, LJ., Meng, Y., Janosczyk, H., et al.[2020]

The albuterol multi-dose dry-powder inhaler (mDPI) simplifies the delivery of medication by eliminating the need for patients to coordinate inhalation with actuation, making it easier for asthma patients to use.

In two studies involving a total of 118 patients, albuterol mDPI demonstrated comparable efficacy and safety to the ProAir HFA metered-dose inhaler, with both treatments significantly improving lung function (FEV1) compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Albuterol (Salbuterol) Multi-dose Dry-Powder Inhaler and ProAir(®) Hydrofluoroalkane for the Treatment of Persistent Asthma: Results of Two Randomized Double-Blind Studies. Kerwin, EM., Taveras, H., Iverson, H., et al.[2022]

The Airmax multidose dry powder inhaler delivering salbutamol is equally effective as the standard pressurized metered dose inhaler (Ventolin) in improving lung function (FEV1) in asthmatic patients, with a 1:1 dose equivalence established in a study of 61 adults.

Both Airmax and Ventolin showed similar safety profiles, and the Airmax inhaler offers advantages such as eliminating the need for coordinated actuation and inhalation, along with a built-in dose counter.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchodilating effects of salbutamol from a novel inhaler Airmax. Middle, MV., Terblanché, J., Perrin, VL., et al.[2019]

In a study involving 21 adult asthmatic patients, a single dose of salbutamol delivered via a novel multiple dose powder inhaler (MDPI) showed equivalent effectiveness in improving lung function compared to a conventional metered dose inhaler (MDI), with similar spirometric outcomes.

Both inhaler types were well tolerated, with no significant effects on blood pressure or heart rate, and most patients found the MDPI easier or equally easy to use, suggesting it could be a favorable alternative to traditional MDIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Easyhaler, a novel multiple dose powder inhaler: clinically equivalent to salbutamol metered dose inhaler and easier to use. Nieminen, MM., Vidgren, M., Laurikainen, K., et al.[2018]

The study aimed to determine if a lower dose combination inhaler of salmeterol and fluticasone (50/250 microg) could provide similar benefits in treating moderate to severe COPD as the higher dose (50/500 microg) inhaler, particularly in improving lung function and reducing exacerbations.

Previous studies have shown that the higher dose inhaler improves forced expiratory volume (FEV1), quality of life, and decreases exacerbations, but most were conducted for less than a year, highlighting the need for longer-term data on the lower dose's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does low-dose seretide reverse chronic obstructive pulmonary disease and are the benefits sustained over time? An open-label Swedish crossover cohort study between 1999 and 2005. Rustscheff, S., Rydén, L.[2017]

The high-dose quadrivalent influenza vaccine (QIV-HD) was approved for individuals 65 years and older, and a review of 2,122 adverse event reports showed that 95.1% were non-serious, aligning with findings from prelicensure trials.

No new safety concerns were identified, with the most common serious events being Guillain-Barré syndrome and local reactions, suggesting that QIV-HD is a safe option for preventing influenza in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety surveillance of high-dose quadrivalent influenza vaccine: Reports to the Vaccine Adverse Event Reporting System. Woo, EJ., Moro, PL.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05215327

High vs. Standard Dose Influenza Vaccine in Lung Allograft ... Lung allograft recipients have a higher burden of influenza disease and greater associated morbidity and mortality compared with healthy controls.

2. cdc.gov cdc.gov/acip/grade/influenza-solid-organ-transplant.html

Higher-Dose and Adjuvanted Influenza Vaccines for Solid ... The purpose of this review was to determine whether there is adequate evidence to support a recommendation that higher dose and adjuvanted influenza vaccines ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522281052

Influenza Vaccination in the Organ Transplant Recipient Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11718019/

Incremental benefit of high dose compared to standard ... A recent meta-analysis study found that the rVE of the HD vaccine compared to the SD varies between 23.3–33.2%. Yet, the evidence for HD vaccine ...

5. academic.oup.com academic.oup.com/cid/article/66/11/1698/4743251

A Double-Blind, Randomized Trial of High-Dose vs Standard ... HD vaccine demonstrated significantly better immunogenicity than SD vaccine in adult transplant recipients and may be the preferred influenza vaccine for this ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04613206

High vs. Standard Dose Influenza Vaccine in Adult SOT ... 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 ...

7. trial.medpath.com trial.medpath.com/clinical-trial/47df071bec3a20fc/nct07192458-immunogenicity-safety-high-dose-standard-dose-influenza-vaccines-lung-transplant

High vs. Standard Dose Influenza Vaccines in Lung ... - MedPath This will be a follow-up study to the "Comparison of High Dose vs. Standard Dose Influenza Vaccine in Lung Allograft Recipient" study (DMID ...