High vs. Standard Dose Flu Vaccine for Transplant Patients

(PSOT Trial)

Recruiting at 9 trial locations

Overseen By Laura Stewart, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Disqualifiers: HIV, Lung transplant, Intestine transplant, 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: 2

Duration: 8 weeks

312 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different doses of the flu vaccine affect children who have undergone kidney, heart, or liver transplants. The main goal is to determine if two high-dose flu shots (High Dose Quadrivalent Inactivated Influenza Vaccine) offer better protection against the flu than two standard-dose shots (Standard Dose Quadrivalent Inactivated Influenza Vaccine). The trial seeks children who are 1 to 23 months post-transplant to help identify the best vaccine strategy for other young transplant recipients. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Earlier studies have found both high-dose and double-dose flu vaccines to be safe and generally well tolerated by transplant recipients, including adults and children. Research on adult solid organ transplant (SOT) recipients showed that the high-dose flu vaccine was safe and led to a stronger immune response compared to the standard dose. A study involving children showed similar results, with the high-dose vaccine being safe and more effective, although the number of participants was small.

Research shows the standard-dose vaccine is also safe for transplant patients. However, the high-dose version usually results in a better immune response without causing more side effects. Both vaccines are generally well tolerated, but the high-dose might offer better protection against the flu for those with weakened immune systems, like transplant recipients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about high dose flu vaccines for transplant patients because they offer a stronger immune response compared to the standard doses. Unlike typical flu vaccines that contain 15µg of each influenza antigen, the high dose version delivers 60µg, potentially boosting the body’s defense system, which is often compromised in transplant patients. This enhanced protection could lead to fewer flu infections and complications, offering a significant advantage over the standard vaccines currently used.

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

This trial will compare the effectiveness of two doses of the High Dose Quadrivalent Inactivated Influenza Vaccine with two doses of the Standard Dose Quadrivalent Inactivated Influenza Vaccine in transplant patients. Research has shown that high-dose flu vaccines generate a stronger immune response than regular-dose vaccines in organ transplant recipients. In adult transplant patients, the high-dose vaccine proved safe and more effective, resulting in higher levels of flu-fighting antibodies. This suggests it could also protect children with weakened immune systems who have had transplants. Previous studies have shown that two doses of the regular vaccine can slightly improve the immune response compared to one dose. However, the high-dose vaccine might offer even better protection. Safety has remained consistent across studies, indicating it is generally well-tolerated. ^{2 5 6 7 8}

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 pediatric solid organ transplant recipients aged 3-17, within 1 to 24 months post-transplant. It includes those who've had kidney, heart, or liver transplants and are available for the study duration. Excluded are patients with recent immune treatments, severe allergies, HIV positive status, pregnancy/lactation in females of childbearing age without a negative pregnancy test prior to each vaccine dose.

Inclusion Criteria

I am between 3 and 17 years old.

I received a kidney, heart, or liver transplant between 1 month and 2 years ago.

Anticipated to be available for duration of the study

Exclusion Criteria

I have had a lung or intestine transplant.

History of severe latex hypersensitivity

I have had Guillain-Barre syndrome in the past.

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 high-dose or standard-dose quadrivalent inactivated influenza vaccine 28-42 days apart

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including active surveillance for influenza-like symptoms

180 days

Weekly telephone/electronic communication

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 High Dose Quadrivalent Inactivated Influenza Vaccine (HD-IIV) provide better immune response compared to Standard Dose (SD) in children who have received an organ transplant less than two years ago. The safety and increase in protective antibodies will be measured.

How Is the Trial Designed?

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

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?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

Lucile Packard Children's Hospital

Collaborator

Trials

16

Recruited

2,800+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Ann & Robert H Lurie Children's Hospital of Chicago

Collaborator

Trials

275

Recruited

5,182,000+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

Children's Mercy Hospital Kansas City

Collaborator

Trials

261

Recruited

941,000+

Children's Healthcare of Atlanta

Collaborator

Trials

172

Recruited

108,000+

Published Research Related to This Trial

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]

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 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]

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]

In a study of 38 patients with Common Variable Immunodeficiency (CVID) who showed a decline in lung function, increasing the dosage of immunoglobulin replacement therapy (IGRT) significantly improved lung function measures (FEF25-75% and FEV1/FVC) in those with moderate obstruction, indicating a potential benefit of dose adjustment.

Patients with severe obstruction did not show improvement with increased IgG dosage, suggesting that higher doses may be more effective for those with moderate lung function decline rather than severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of FEF25-75% to Guide IgG Dosing to Protect Pulmonary Function in CVID. Hwangpo, T., Wang, Z., Ghably, J., et al.[2021]

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 of 40 CMV seronegative renal transplant recipients receiving polyvalent intravenous immunoglobulins (IVIg) as prophylaxis, 95% had successful one-year allograft survival, indicating that IVIg is effective in preventing CMV infection and supporting graft health.

The use of IVIg resulted in excellent tolerance with no acute renal failure episodes, suggesting it is a safe option for high-risk patients, and it may also help reduce the incidence of acute rejection, warranting further investigation in randomized studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytomegalovirus prophylaxis with intravenous polyvalent immunoglobulin in high-risk renal transplant recipients. Leroy, F., Sechet, A., Abou Ayache, R., et al.[2006]

In a study of 17 renal transplant patients, administering a short-term high-dose IVIG regimen (4 g/kg total) resulted in 47.1% achieving negative T cell crossmatch status, indicating potential desensitization to donor-specific antibodies.

The cumulative T cell crossmatch-negative conversion rate increased with higher IVIG doses, suggesting that a total dose of 3 g/kg or more may be more effective than the conventional 2 g/kg single-dose protocol for desensitizing patients before transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Desensitization of T cell Flow Cytometry Crossmatch Positive Renal Transplant Recipients Using Plasmapheresis and Super High-Dose Intravenous Immunoglobulin. Kakuta, Y., Satoh, S., Watarai, Y., et al.[2022]

In a study involving five patients with severe chronic systemic diseases, high dose intravenous immunoglobulin (IV Ig) treatment (2g/kg/session) showed little to no improvement in their conditions, with only one patient experiencing a transient response.

The inconsistent results and high cost of IV Ig highlight the need for double-blind studies to better understand when this treatment may be more effective than standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Failure of intravenous immunoglobulins in certain systemic diseases. 5 cases]. Bahadoran, P., De Bandt, M., Echard, M., et al.[2016]

Citations

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Fluzone High-Dose Seasonal Influenza Vaccine A randomized efficacy study published in the New England Journal of Medicine indicated that the trivalent high-dose vaccine was 24% more ...

2. journalofinfection.com journalofinfection.com/article/S0163-4453(25)00132-X/fulltext

High-dose versus standard-dose influenza vaccine for ... Conclusions. High-dose influenza vaccine showed higher immunogenicity and similar safety than standard-dose vaccine and should be recommended ...

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

Incremental benefit of high dose compared to standard ... Evidence regarding the high-dose (HD) vaccine's relative vaccine effectiveness (rVE) and absolute benefit in reducing influenza-related hospitalizations

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04613206

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

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11779186/

592. Immunogenicity and Safety of High-dose versus ... Both high-dose and double-dose inactivated influenza vaccines have been shown to better elicit a greater immune response compared to standard-dose influenza ...

7. 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 ...

8. academic.oup.com academic.oup.com/ofid/article/12/Supplement_1/ofae631.187/7988732

592. Immunogenicity and Safety of High-dose versus Double ... Both high-dose and double-dose inactivated influenza vaccines have been shown to better elicit a greater immune response compared to standard- ...