High vs Standard Dose Flu Vaccine for Lung Transplant Recipients
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Vanderbilt University Medical Center
Must not be taking: B-cell depleting, T-cell depleting
Disqualifiers: Multi-organ transplant, HIV, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?Lung allograft recipients have a higher burden of influenza disease and greater associated morbidity and mortality compared with healthy controls. Induction and early maintenance immunosuppression is thought to impair immunogenicity to standard dose inactivated influenza vaccine. This early post-transplant period is when immunity is most desirable, since influenza disease during this time frame is associated with adverse consequences. Thus, strategies to reduce severe influenza disease in this highly susceptible population are critical. No trials in lung transplant recipients have evaluated two doses of HD-IIV within the same influenza season as a strategy to improve immunogenicity and durability of influenza prevention. Furthermore, no influenza vaccine trials have focused on enrollment of subjects at early post-transplant timepoints. Very few studies have been performed in solely lung allograft recipients. Immunosuppression intensity is highest in lung patients, thereby limiting comparisons to recipients of heart, liver, and kidney transplants. Therefore, studies to assess both HD-IIV and two-dose strategies in the same influenza season in post-lung transplant recipients are greatly needed.
The central hypothesis of our proposal is that lung allograft recipients who are 1-35 months post-transplant and receiving two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have higher HAI geometric mean titers (GMT) to influenza antigens compared to those receiving two doses of SD-QIV. To test this hypothesis and address the above critical knowledge gaps, we propose to conduct a phase II, multi-center, randomized, double-blind, controlled immunogenicity and safety trial comparing the administration of two doses of HD-QIV to two doses of SD-QIV in lung allograft recipients 1-35 months post-transplant. The results of this clinical trial will address significant knowledge gaps regarding influenza vaccine strategies (e.g., one vs. two doses and HD-QIV vs. SD-QIV) and immune responses in lung transplant recipients and will guide vaccine recommendations during the post-transplant period.
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.
What data supports the effectiveness of the high-dose flu vaccine for lung transplant recipients?
Research shows that the high-dose flu vaccine provides better protection against the flu compared to the standard-dose vaccine, especially in older adults. This suggests it might also be more effective for lung transplant recipients, who often have weakened immune systems.
12345Is the high-dose flu vaccine generally safe for humans?
The high-dose flu vaccine, known as Fluzone High-Dose, has been studied for safety in older adults. Most reported side effects are mild, like injection site reactions, fever, headache, and nausea, with serious events being rare. No new safety concerns have been identified.
12346How does the flu vaccine for lung transplant recipients differ from other flu vaccines?
The flu vaccine for lung transplant recipients in this trial uses a high dose of the quadrivalent inactivated influenza vaccine, which is designed to provide stronger protection compared to the standard dose, potentially offering better immunity for those with weakened immune systems.
7891011Eligibility Criteria
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.
+2 more
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.
+10 more
Trial Timeline
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)
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Two Doses Standard Dose Quadrivalent Inactivated Influenza VaccineExperimental Treatment1 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 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:
Vanderbilt University Medical CenterNashville, TN
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Who Is Running the Clinical Trial?
Vanderbilt University Medical CenterLead Sponsor
Feinberg School of Medicine, Northwestern UniversityCollaborator
Northwestern University Feinberg School of MedicineCollaborator
University of WashingtonCollaborator
Duke UniversityCollaborator
University of Alabama at BirminghamCollaborator
References
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
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.
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.
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. [2023]A high-dose, split-virion inactivated quadrivalent influenza vaccine (IIV4-HD; Sanofi) is being used for the prevention of influenza in multiple countries. This study examined the immunogenicity and safety of the IIV4-HD vaccine administered intramuscularly (IM) compared with a locally licensed standard-dose influenza vaccine (IIV4-SD) administered subcutaneously (SC) in Japan.
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).
The dose-response characteristics of inhaled corticosteroids when used to treat asthma: an overview of Cochrane systematic reviews. [2022]Inhaled corticosteroids form the cornerstone of treatment for most patients with asthma. A range of compounds are available with a wide range of prescribable doses. In this overview, we summarize the findings from a number of Cochrane systematic reviews that have examined the relative benefits of different doses of beclometasone dipropionate, budesonide and fluticasone propionate when used to treat children and adults. The key findings are that all inhaled corticosteroids demonstrate a dose-response relationship for efficacy measures, but most of the benefit in mild-to-moderate severity disease is gained in the low-to-moderate dose range of each drug. In this group, high doses of fluticasone lead to small improvements in measures of control at the expense of a steep increase in the incidence of oral side-effects. In patients with severe disease who are dependent on oral steroids, there may be appreciable benefit in reducing oral steroids from very high compared with high doses of fluticasone.
Bronchodilating effects of salbutamol from a novel inhaler Airmax. [2019]This randomized, placebo-controlled, evaluator-blind, five-way crossover study compared the equivalence in terms of FEV1 response to single ascending cumulative doses of salbutamol (100-400 micrograms) from Airmax, a new multidose dry powder inhaler, in comparison with placebo, the same dose from a standard pressurized metered dose inhaler (Ventolin) or at double the dose from the dry powder inhalers Diskhaler and Accuhaler. Sixty-one adult asthmatic subjects with FEV150-80% predicted and > or = 15% increase in FEV1 to salbutamol took part. Equivalence was declared if the 95% CI for the ratio of the FEV1 responses to the two treatments was within the range 90-111%. Following the cumulative four doses, FEV1 (1) changes pre-dose to the highest dose were: 2.53-3.31, 2.47-3.30, 2.51-3.35, 2.52-3.31 and 2.57-2.55 for Airmax salbutamol, salbutamol Ventolin, salbutamol Diskhaler, salbutamol Accuhaler and placebo, respectively. The 95% CIs for the ratio of Airmax salbutamol to each of the active devices were within +/- 5% demonstrating a 1:1 dose equivalence between Airmax salbutamol and Ventolin and a 1:2 dose equivalence between each of the other two salbutamol dry powder devices. Adverse events profiles were similar for all treatments. In conclusion, the novel multidose inhaler Airmax salbutamol is as efficacious and safe as the pressurized metered dose inhaler without the need for co-ordinating actuation and inhalation and with the added benefit of a dose counter.
Easyhaler, a novel multiple dose powder inhaler: clinically equivalent to salbutamol metered dose inhaler and easier to use. [2018]Twenty-one adult asthmatic patients participated in a trial to compare the clinical equivalence of a single dose of salbutamol inhaled either from a novel multiple dose powder inhaler (MDPI), Easyhaler, or from a conventional metered dose inhaler (MDI). The trial was carried out as a randomized, double-blind, crossover study. The study involved 2 study days with a 6-hour follow-up period of spirometric indices. In addition, blood pressure and heart rate were measured immediately before each lung function test. Our data indicate that salbutamol treatment with the MDPI achieves values which are equivalent to those achieved with the conventional pressurized MDI as regards improving pulmonary function and tolerability. The mean maximum forced expiratory volume in 1 s (FEV1) after the powder dose was 2.44 +/- 0.96 liters and after the aerosol dose 2.45 +/- 0.93 liters. The mean area under the curve of absolute FEV1 values was 822 +/- 340 and 829 +/- 335, respectively. The mean percent change from the baseline in FEV1, forced vital capacity and peak expiratory flow following administration of the preparations was of equal magnitude in both cases. The treatments tested had no effect on blood pressure or heart rate and were well tolerated. A further important finding was that most patients found the MDPI easier or no more difficult to use than the conventional MDI and this probably facilitates the transition from pressurized MDIs to the novel MDPI.
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]Chronic obstructive pulmonary disease (COPD) still poses a formidable challenge to patients and clinicians alike. A fixed-dose dry powder combination inhaler, Seretide/Advair, containing salmeterol and fluticasone, is licensed in the European Community for the treatment of moderate to severe COPD in the strength of 50/500 microg twice daily (BID). Several studies have investigated the effects of this combination and show improved forced expiratory volume in 1 s (FEV(1)), quality of life, and a decrease of exacerbations. Most of the studies have run for less than 1 year. The aim of this investigator-initiated, independent study was to elucidate if the combination containing 50 microg of salmeterol and 250 microg of fluticasone BID could be shown to have the same beneficial effect as the higher dosage, and if the effect could be sustained over time.
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. [2022]Metered-dose inhalers require patients to coordinate inhalation with actuation. The present albuterol multi-dose dry-powder inhaler (mDPI) does not require patients to coordinate inspiration with actuation, thereby simplifying delivery of albuterol to the lungs. The aim of the present study was to compare the efficacy, pharmacokinetics, pharmacodynamics, extrapulmonary pharmacodynamics, and safety of albuterol (salbuterol) delivered via a ProAir® hydrofluoroalkane (HFA) metered-dose inhaler and an mDPI.