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

Goal: 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. 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.

Background: The 5.8 million Individuals in the US with heart failure (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.

Preliminary data: Our research group at UW Madison has demonstrated reduced antibody titers
to influenza vaccination in patients with HF. Additionally, we've shown in a pilot study that
double dose influenza vaccine resulted in increased titers and was well tolerated.

Methods: A multi-center, prospective, randomized, open-label blinded-endpoint trial will be
conducted with 20 patients assigned to the standard dose vaccine dose and 20 patients 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.

Inclusion Criteria:

1. Adults > 18 years old

2. Able to give informed consent

3. Systolic or diastolic dysfunction

4. Previously or currently symptomatic heart failure

5. Stable on current heart failure drug therapy regimen for > 30 days and no change in
heart failure drug therapy regimen on day of enrollment

6. Hospitalization (for any reason) in last 12 months

7. Received influenza vaccination the prior season

Exclusion Criteria:

1. History of allergic reaction or adverse event to influenza vaccine

2. Documented severe allergy to egg products

3. Unwilling or unable to give consent

4. Moderate to severe acute febrile illness at baseline

5. Immunologic conditions that may affect immune responses per clinical judgment of the
investigators

6. Use of immunosuppressants or immunomodulating therapies within 3 months of the study,
including prednisone, cyclosporine, tacrolimus, methotrexate, azathioprine,
mycophenolate mofetil, cyclophosphamide, and injectable interferons

7. Participation in a clinical trial within 30 days

8. Absence for more than 7 consecutive days during the surveillance period