VAccination to Improve Clinical outComes in Heart Failure Trial: a Feasibility Study (VACC-HeFT)

Study Overview
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Brief Summary
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A multi-center, prospective, randomized, open-label blinded-endpoint trial in patients with heart failure will be conducted; 20 will be assigned to the standard dose vaccine dose and 20 patients to high dose influenza vaccine. Post-vaccine antibody measurements will be assessed, as well as tolerability differences between groups.

Detailed Description
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This is a randomized, double blind, active-control trial of high dose influenza vaccine compared to standard dose influenza vaccine for one season in adult participants with symptomatic heart failure(HF). The primary outcome measure is humoral (antibody-mediated) immune response, and secondary outcomes include cumulative incidence of influenza-like illness symptoms and all cause hospitalizations. The aim is to gather information on feasibility of this study design and effect size differences to inform a larger outcomes-based clinical trial. The 5.8 million Individuals in the US with heart HF are at high risk for influenza infection and associated morbidity, mortality and increased health care costs despite annual influenza vaccination. Higher dose of vaccine is approved for use in older adults. Antibody-mediated immunity contributes to vaccine-induced protection from influenza illness. Investigators at University of Wisconsin(UW) Madison have demonstrated reduced antibody titers to influenza vaccination in patients with HF. Additionally, study team has shown in a pilot study that double dose influenza vaccine resulted in increased titers and was well tolerated. A multi-center, prospective, randomized, open-label blinded-endpoint trial will be conducted with 20 participants assigned to the standard dose vaccine dose and 20 participants to high dose influenza vaccine. The primary outcome measure is the rate of seroconversion (4-fold rise in antibody titers to A/H3N2, A/H1N1, and B-type vaccine antigens), assessed 4 weeks post vaccination. The study will also examine feasibility differences in symptoms of influenza and all-cause hospitalizations between vaccine dose groups, and these data will be used for planning a subsequent outcomes-based clinical trial.

Official Title
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VAccination to Improve Clinical outComes in Heart Failure Trial (VACC-HeFT): a Feasibility Study

Conditions
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Chronic Heart Failure

Intervention / Treatment
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* Biological: Influenza vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults > 18 years old Able to give informed consent Systolic or diastolic dysfunction Previously or currently symptomatic heart failure Stable on current heart failure drug therapy regimen for > 30 days and no change in heart failure drug therapy regimen on day of enrollment Hospitalization (for any reason) in last 12 months Received influenza vaccination the prior season Exclusion Criteria: History of allergic reaction or adverse event to influenza vaccine Documented severe allergy to egg products Unwilling or unable to give consent Moderate to severe acute febrile illness at baseline Immunologic conditions that may affect immune responses per clinical judgment of the investigators Use of immunosuppressants or immunomodulating therapies within 3 months of the study, including prednisone, cyclosporine, tacrolimus, methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, and injectable interferons Participation in a clinical trial within 30 days Absence for more than 7 consecutive days during the surveillance period

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard dose influenza vaccine<br>Standard dose (45ug) influenza vaccine will be administered intramuscularly | Biological: Influenza vaccine<br>* Influenza vaccine<br>* Other names: Fluzone;|
| Active Comparator: High dose influenza vaccine<br>High dose (180ug) influenza vaccine will be administered intramuscularly | Biological: Influenza vaccine<br>* Influenza vaccine<br>* Other names: Fluzone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With 4 Fold Rise in Serum Antibody Concentration of A/H1N1 Vaccine Antigens |  | 4 weeks | 
| Number of Participants With 4 Fold Rise in Serum Antibody Concentration of A/H3N2 Vaccine Antigens |  | 4 weeks | 
| Number of Participants With 4 Fold Rise in Serum Antibody Concentration of B-type Vaccine Antigens |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Influenza Like Illness | Influenza Like Illness is not considered adverse event. | 8 months | 
| Number of All-cause Hospitalizations | All-cause hospitalizations are not considered adverse events. | 8 months |