High vs. Standard Dose Flu Vaccine for Transplant Patients (PSOT Trial)
Palo Alto (17 mi)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)
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.
Is the High Dose Flu Vaccine a promising treatment for transplant patients?Yes, the High Dose Flu Vaccine is promising for transplant patients because it is designed to provide stronger protection against the flu, which is important for people with weakened immune systems, like those who have had transplants.12346
What safety data exists for high-dose flu vaccines in transplant patients?The high-dose quadrivalent influenza vaccine (Fluzone High-Dose Quadrivalent, QIV-HD) has been studied primarily in adults aged 65 and older. Safety data from a prelicensure trial and postmarketing surveillance indicate that most adverse events are non-serious, such as injection site reactions, fever, headache, and nausea. Serious events reported include Guillain-Barré syndrome, cellulitis, and cardiovascular events, but no new safety concerns were identified. These findings can help inform vaccination strategies for transplant patients.578910
What data supports the idea that High vs. Standard Dose Flu Vaccine for Transplant Patients is an effective treatment?The available research shows that the high-dose flu vaccine is generally more effective than the standard-dose vaccine, especially in older adults. For example, a study in Taiwan found that the high-dose vaccine provided better protection against the flu and its complications compared to the standard-dose version. Additionally, safety reviews indicate that most side effects of the high-dose vaccine are mild, such as injection site reactions and fever, with no new safety concerns identified. This suggests that the high-dose vaccine is a safe and effective option for preventing the flu in older adults.578910
Do I have to stop taking my current medications for the trial?The trial protocol does not specify whether you need to stop taking your current medications. However, it is important to discuss your current medications with the study team to ensure they do not interfere with the trial.
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.Treatment Details
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.
2Treatment groups
Experimental Treatment
Group I: Two Doses Standard Dose Quadrivalent Inactivated Influenza VaccineExperimental Treatment1 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 VaccineExperimental Treatment1 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Monroe Carell Jr. Children's Hospital at VanderbiltNashville, TN
UPMC Children's Hospital of PittsburghPittsburgh, PA
Texas Children's HospitalHouston, TX
Vanderbilt University Medical CenterNashville, TN
More Trial Locations
Loading ...
Who is running the clinical trial?
National Institute of Allergy and Infectious Diseases (NIAID)Lead Sponsor
Vanderbilt University Medical CenterLead Sponsor
Children's Hospital Medical Center, CincinnatiCollaborator
Lucile Packard Children's HospitalCollaborator
University of PittsburghCollaborator
Ann & Robert H Lurie Children's Hospital of ChicagoCollaborator
Baylor College of MedicineCollaborator
Children's Mercy Hospital Kansas CityCollaborator
Children's Healthcare of AtlantaCollaborator
References
[Failure of intravenous immunoglobulins in certain systemic diseases. 5 cases]. [2016]Human polyvalent immunoglobulins administered intravenously have shown to be effective in some immune diseases. We administered high dose-IV Ig (2g/kg/session) in five patients with severe chronic systemic diseases. Their condition did not improve, except in one case where a transient response was noticed. Considering the inconsistent results and high cost of IV Ig, double blind studies are required to determine the conditions in which high dose IV Ig may be more effective than conventional treatments.
Cytomegalovirus prophylaxis with intravenous polyvalent immunoglobulin in high-risk renal transplant recipients. [2006]Cytomegalovirus (CMV) seronegative renal allograft recipients (R-), particularly those with a graft from a CMV-seropositive donor (D+), are at high risk for primary CMV infection. CMV resistance to antiviral oral therapy is an emerging problem in renal transplantation, prompting development of new prophylactic strategies. We retrospectively studied the 1-year posttransplantation incidence of CMV infection in high-risk renal transplant recipients, in whom polyvalent intravenous immunoglobulins (IVIg) were used as prophylaxis. Forty R- patients received immunoprophylaxis by polyvalent IVIg (0.25 g/kg weekly for 8 weeks, starting on the operative day). CMV serological tests remained negative in eight patients (20%). Eight patients (20%) had asymptomatic CMV infection while 24 (60%) developed CMV syndrome and were treated with gancyclovir (10 mg/kg/day intravenously for 3 weeks). None had CMV disease or opportunistic infection. Six patients (15%) had biopsy-proven acute rejection, which followed CMV syndrome in three cases. One-year renal allograft and patient survivals were 95% and 97.5%, respectively. Mean serum creatinine level was 124 +/- 33 micromol/L at 1 year. Clinical tolerance of IVIg was excellent, without any episode of acute renal failure. Polyvalent IVIg provides effective prophylaxis in renal transplant recipients at high risk for CMV infection and is associated with excellent 1-year allograft survival. Because of their immunomodulatory functions, IVIg may have a beneficial effect on the incidence of acute and chronic rejection and allograft survival. A randomized prospective study is required to evaluate long-term effects of CMV prophylaxis with polyvalent IVIg compared to antiviral agents in renal transplant recipients.
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]To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza.
Successful Desensitization of T cell Flow Cytometry Crossmatch Positive Renal Transplant Recipients Using Plasmapheresis and Super High-Dose Intravenous Immunoglobulin. [2022]High-dose IVIG (2 g/kg) alone or low-dose IVIG (100 mg/kg) in conjunction with plasma exchange is typically administered as a renal transplantation desensitization therapy. Herein, we monitored changes in T cell and B cell flow cytometry crossmatch (FCXM) to assess the effects of short-term super high-dose IVIG (4 g/kg) administration with plasmapheresis before living-donor renal transplantation.
Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: A phase 3 randomized clinical trial. [2020]A high-dose, split-virion inactivated trivalent influenza vaccine (IIV3-HD; Fluzone® High-Dose, Sanofi Pasteur) is available for adults ≥65 years of age. This study examined the safety and immunogenicity of a quadrivalent high-dose split-virion inactivated influenza vaccine (IIV4-HD).
Use of FEF25-75% to Guide IgG Dosing to Protect Pulmonary Function in CVID. [2021]Immunoglobulin replacement therapy (IGRT) can protect against lung function decline in CVID. We tested whether increasing IgG dosage was beneficial in patients who exhibited a decline in forced expiratory flow at 25-75% (FEF25-75%) even though they were receiving IgG doses within the therapeutic range. Of 189 CVID patients seen over 12 years, 38 patients met inclusion criteria, were seen on ≥ 3 visits, and demonstrated a ≥ 10% decrease in FEF25-75% from visits 1 to 2. FEF25-75%, forced expiratory flow at 1 s (FEV1), and FEV1/FVC at visit 3 were compared among those with non-dose adjustment (non-DA) versus additional IgG dose adjustment (DA). Three FEF25-75% tiers were identified: top (> 80% predicted), middle (50-80%), and bottom (
High-Dose Inactivated Influenza Vaccine Quadrivalent for Older Adults. [2021]To review the efficacy and safety of the high-dose inactivated influenza vaccine quadrivalent (HD-IIV4) in the prevention of influenza in older adults.
Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through [2021]Quadrivalent high-dose inactivated influenza vaccine (Fluzone® High-Dose Quadrivalent, IIV4-HD) was licensed in the USA in 2019 for adults ≥ 65 years of age. This Phase II study examined safety and immunogenicity of 3 dose formulations of IIV4-HD in healthy children. In a randomized, modified double-blind, active-controlled trial in the USA and Canada, 661 children aged 6 months through
Postmarketing safety surveillance of high-dose quadrivalent influenza vaccine: Reports to the Vaccine Adverse Event Reporting System. [2022]On November 4, 2019, the Food and Drug Administration approved high-dose quadrivalent influenza vaccine (Fluzone High-Dose Quadrivalent; QIV-HD) for active immunization for the prevention of influenza disease in individuals 65 years of age and older. A prelicensure randomized, active-controlled, modified double-blind trial did not reveal any major differences in adverse events following QIV-HD versus Fluzone High-Dose (trivalent). To improve our understanding of the safety profile of QIV-HD, we reviewed and summarized reports of adverse events after QIV-HD to the Vaccine Adverse Event Reporting System (VAERS). From July 30, 2020 through June 30, 2021, VAERS received 2,122 reports after QIV-HD. The vast majority (2,018; 95.1%) were non-serious and included events that had been observed in the prelicensure clinical trial, such as injection site reactions, fever, headache, and nausea. The most common serious events included Guillain-Barré syndrome, cellulitis or other local reactions, constitutional signs/symptoms (e.g., fever), and cardiovascular events. Our review did not reveal any new safety concerns. This information may enable policy makers, health officials, clinicians, and patients to make a more informed decision regarding vaccination strategies.
Immunogenicity and safety of high-dose quadrivalent influenza vaccine in older adults in Taiwan: A phase III, randomized, multi-center study. [2023]High-dose influenza vaccine offers better protection against influenza/associated complications compared with standard-dose formulation. We evaluated immunogenicity and safety of high-dose influenza vaccine (QIV-HD) and standard-dose (QIV-SD) in older adults (≥ 65 years) in Taiwan.