High vs. Standard Dose Flu Vaccine for Transplant Patients

(PSOT Trial)

Recruiting in Palo Alto (17 mi)

+9 other locations

Overseen by Natasha Halasa, MD, MPH

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Disqualifiers: HIV, Lung transplant, Intestine transplant, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Influenza virus is a significant pathogen in pediatric solid organ transplant (SOT) recipients. However, these individuals respond poorly to standard-dose (SD) inactivated influenza vaccine (IIV). 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 and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza season. One study compared HD-IIV vs. SD-IIV in adult SOT recipients and noted that HD-IIV was safe and more immunogenic; however, the median post-transplant period was 38 months. A phase I pediatric study comparing a single dose of HD-IIV vs. SD-IIV was safe with higher immunogenicity, but the study was limited by small sample size and median post-transplant vaccine administration was 26 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV one month apart compared to one-dose of SD-IIV revealed modestly increased immunogenicity when given at a median of 18 months post-transplant. Therefore, these studies lack both evaluation in the early post-transplant period and substantive pediatric populations. Additionally, the administration of two-doses of HD-IIV in the same influenza season has not been evaluated in pediatric SOT recipients. Thus, the optimal immunization strategy for pediatric SOT recipients less than 24 months post-transplant is unknown. In addition, immunologic predictors and correlates of influenza vaccine immunogenicity in pediatric SOT recipients have not been well-defined. The central hypothesis of our proposal is that pediatric SOT recipients 1-23 months post-transplant who receive two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have similar safety but higher Hemagglutination Inhibition (HAI) geometric mean titers (GMTs) to influenza antigens compared to pediatric SOT recipients receiving two doses of SD-QIV.

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 the high-dose flu vaccine safe for humans?

The high-dose flu vaccine, known as Fluzone High-Dose, has been studied in both children and adults, particularly those 65 and older. Most reported side effects are mild, like injection site reactions, fever, headache, and nausea, with serious events being rare. Overall, no new safety concerns have been identified, suggesting it is generally safe for use. ^{1 2 3 4 5}

How does the high dose flu vaccine differ from standard treatments for transplant patients?

The high dose flu vaccine is unique because it contains a higher amount of antigen (the part of the vaccine that helps your body build protection) compared to the standard dose, which may provide better protection for transplant patients who have weakened immune systems. ^{6 7 8 9 10}

Research Team

Natasha Halasa, MD, MPH

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

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.

I have received a transplant for my kidney, heart, or liver.

Exclusion Criteria

I have had a lung or intestine transplant.

History of severe latex hypersensitivity

I have had Guillain-Barre syndrome in the past.

Trial Timeline

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

Treatment Details

Interventions

• High Dose Quadrivalent Inactivated Influenza Vaccine (Virus Therapy)
• Standard Dose Quadrivalent Inactivated Influenza Vaccine (Virus Therapy)

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.

Participant Groups

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 Canada for the following indications:

Approved in Canada as Fluzone High-Dose for:

• Influenza prevention in individuals 65 years and older

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Monroe Carell Jr. Children's Hospital at Vanderbilt Nashville, TN

UPMC Children's Hospital of Pittsburgh Pittsburgh, PA

Texas Children's Hospital Houston, TX

Stanford University Stanford, CA

More Trial Locations

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3361

Patients Recruited

5,516,000+

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Patients Recruited

939,000+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Patients Recruited

6,566,000+

Lucile Packard Children's Hospital

Collaborator

Trials

16

Patients Recruited

2,800+

University of Pittsburgh

Collaborator

Trials

1820

Patients Recruited

16,360,000+

Ann & Robert H Lurie Children's Hospital of Chicago

Collaborator

Trials

275

Patients Recruited

5,182,000+

Baylor College of Medicine

Collaborator

Trials

1044

Patients Recruited

6,031,000+

Children's Mercy Hospital Kansas City

Collaborator

Trials

261

Patients Recruited

941,000+

Children's Healthcare of Atlanta

Collaborator

Trials

172

Patients Recruited

108,000+

Findings from Research

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]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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]

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]

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]

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]

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

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

4. 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]

5. Netherlands 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. [2023]

6. 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]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Use of FEF25-75% to Guide IgG Dosing to Protect Pulmonary Function in CVID. [2021]

8. France pubmed.ncbi.nlm.nih.gov

[Failure of intravenous immunoglobulins in certain systemic diseases. 5 cases]. [2016]

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

Cytomegalovirus prophylaxis with intravenous polyvalent immunoglobulin in high-risk renal transplant recipients. [2006]

10. United States 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. [2022]