High-Dose Flu Vaccine for Solid Organ Transplant Recipients

Overseen By Hareesh Singam, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Must not be taking: ATG, Carfilzomib, Rituximab, others

Disqualifiers: Pregnancy, Severe allergy, Prednisone, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

100 Participants Needed

Trial Summary

What is the purpose of this trial?

In solid organ transplant (SOT) the receipt of influenza vaccine in an influenza season is associated with decreased disease severity as demonstrated by the presence of pneumonia and ICU admissions. Different strategies have been assessed to optimize vaccine efficacy and immunogenicity of the influenza vaccine in the solid organ transplant recipient (SOTR). The primary objective of the study is to evaluate the immunogenicity of 2 doses of the high dose influenza vaccine utilizing neutralizing antibody assays. A control group receiving 1 HD influenza vaccine will be included.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you have received certain medications like ATG, carfilzomib, rituximab, or basiliximab in the past 3 months, you cannot participate.

Is the high-dose flu vaccine safe for humans?

The high-dose flu vaccine, known as Fluzone High-Dose Quadrivalent, has been studied for safety in both children and adults. Most reported side effects are mild, such as injection site reactions, fever, headache, and nausea. Serious side effects are rare, and no new safety concerns have been identified in recent reviews. ^{1 2 3 4 5}

How does the drug Fluzone High-Dose Quadrivalent differ from other treatments for solid organ transplant recipients?

Fluzone High-Dose Quadrivalent is unique because it contains a higher dose of the flu vaccine specifically designed to provide better protection for people with weakened immune systems, such as solid organ transplant recipients, compared to standard flu vaccines. ^{6 7 8 9 10}

Research Team

Lauren Fontana, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for adults over 18 who had a solid organ transplant (like liver, lung, heart, kidney, pancreas) more than a year ago. They must be able to consent and participate in all study activities. People can't join if they've recently received certain immune therapies or high-dose steroids, are pregnant, or have had severe allergies to flu vaccines.

Inclusion Criteria

I had my transplant surgery over a year ago.

I am willing and able to follow all study requirements.

Able and willing to provide informed consent

Exclusion Criteria

I have received basiliximab in the last 3 months.

I have received ATG or carfilzomib in the last 3 months.

You are pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either one or two doses of the high dose influenza vaccine, with a control group receiving a placebo after the first dose

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of pneumonia, hospitalization, ICU admissions, and death rates

2 years

Treatment Details

Interventions

• Fluzone High-Dose Quadrivalent

Trial Overview The trial is testing the effectiveness of giving two doses of Fluzone High-Dose Quadrivalent influenza vaccine compared to just one dose in people who have received solid organ transplants. The goal is to see which strategy better stimulates the body's defenses against the flu.

Participant Groups

Group I: booster group Experimental Treatment 1 Intervention

Participants who have undergone a solid organ transplant will receive two doses of an inactivated high dose influenza vaccine

Group II: Control group Active Control 1 Intervention

Participants who have undergone a solid organ transplant will receive one dose of inactivated high dose influenza vaccine followed by a placebo injection

Fluzone High-Dose Quadrivalent is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Fluzone High-Dose Quadrivalent for:

• Prevention of disease caused by influenza A subtype viruses and type B virus

Approved in European Union as Fluzone High-Dose Quadrivalent for:

• Prevention of disease caused by influenza A subtype viruses and type B virus

Approved in Canada as Fluzone High-Dose Quadrivalent for:

• Prevention of disease caused by influenza A subtype viruses and type B virus

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

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]

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]

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 Fluzone® Quadrivalent (IIV4) vaccine was monitored for safety in pregnant women, with 239 exposure reports collected from August 2013 to September 2019, showing no new safety concerns related to maternal or neonatal outcomes.

Among the reported outcomes, over 85% of neonates were full-term births, and all infants with available information had normal APGAR scores, indicating that the vaccine is safe for use during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to quadrivalent influenza vaccine during pregnancy: Results from a global pregnancy registry. Ledlie, S., Gandhi-Banga, S., Shrestha, A., et al.[2022]

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 of 189 patients receiving fluticasone propionate and salmeterol combination inhalers, 19.6% had at least one inhaler dispensed unnecessarily, leading to significant waste.

Overall, 76.3% of doses dispensed were wasted, costing the healthcare system over $5,151 CAD, highlighting the need for improved procedures to manage inhaler transfers and inventory to reduce waste.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cautionary tale of multiple-dose drug products: Fluticasone and salmeterol combination inhaler waste. Aeng, ESY., Dhaliwal, MM., Tejani, AM.[2021]

In a study involving 326 patients with severe influenza across multiple hospitals in Southeast Asia, doubling the dose of oseltamivir (150 mg twice a day) did not show any significant virological or clinical benefits compared to the standard dose (75 mg twice a day).

Both treatment groups had similar rates of viral clearance and mortality, indicating that higher doses of oseltamivir may not be necessary or more effective for treating severe influenza.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial. [2021]

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]

In a study involving 133 adult asthmatics, fluticasone propionate (FP) was found to be at least as effective as beclomethasone dipropionate (BDP) and budesonide (BUD) in managing severe asthma, while potentially offering better safety regarding steroid-related side effects.

Patients switched to FP experienced significant increases in morning serum cortisol levels and improved quality of life scores, suggesting that FP may have a more favorable safety profile compared to high-dose BDP or BUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate. Berend, N., Kellett, B., Kent, N., et al.[2019]

Wixela Inhub demonstrated pharmacokinetic bioequivalence to Advair Diskus for both fluticasone propionate (FP) and salmeterol across all tested doses (100/50, 250/50, and 500/50 μg) in a study involving 66 healthy subjects per dose, confirming its effectiveness as a generic alternative.

Both Wixela Inhub and Advair Diskus were well tolerated, indicating that Wixela Inhub not only matches the efficacy of Advair Diskus but also maintains similar safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equivalent Systemic Exposure to Fluticasone Propionate/Salmeterol Following Single Inhaled Doses from Advair Diskus and Wixela Inhub: Results of Three Pharmacokinetic Bioequivalence Studies. Haughie, S., Allan, R., Wood, N., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

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

3. Netherlands 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. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Exposure to quadrivalent influenza vaccine during pregnancy: Results from a global pregnancy registry. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

A cautionary tale of multiple-dose drug products: Fluticasone and salmeterol combination inhaler waste. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial. [2021]

8. England 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. [2017]

9. Australia pubmed.ncbi.nlm.nih.gov

Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Equivalent Systemic Exposure to Fluticasone Propionate/Salmeterol Following Single Inhaled Doses from Advair Diskus and Wixela Inhub: Results of Three Pharmacokinetic Bioequivalence Studies. [2021]