Chronic Heart Failure
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALInfluenza vaccine
Influenza vaccine
Sponsors
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Influenza Like Illness | 8 months | Influenza Like Illness is not considered adverse event. |
| Number of All-cause Hospitalizations | 8 months | All-cause hospitalizations are not considered adverse events. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Dose Influenza Vaccine Standard dose (45ug) influenza vaccine will be administered intramuscularly
Influenza vaccine: Influenza vaccine | 24 |
| High Dose Influenza Vaccine High dose (180ug) influenza vaccine will be administered intramuscularly
Influenza vaccine: Influenza vaccine | 24 |
| Total | 48 |
Baseline characteristics
| Characteristic | Standard Dose Influenza Vaccine | High Dose Influenza Vaccine | Total |
|---|---|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 12.2 | 62.5 years STANDARD_DEVIATION 13.1 | 59.45 years STANDARD_DEVIATION 12.7 |
| Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) users | 23 Participants | 23 Participants | 46 Participants |
| Aspirin users | 12 Participants | 20 Participants | 32 Participants |
| Beta blocker users | 22 Participants | 23 Participants | 45 Participants |
| Body mass index (BMI) | 33.7 kg/m^2 STANDARD_DEVIATION 10 | 30.9 kg/m^2 STANDARD_DEVIATION 6.8 | 32.3 kg/m^2 STANDARD_DEVIATION 8.4 |
| Diuretic users | 20 Participants | 19 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 24 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Left Ventricular Ejection Fraction (LVEF) percentage | 38.8 percentage of ejection fraction STANDARD_DEVIATION 9.8 | 40.3 percentage of ejection fraction STANDARD_DEVIATION 10.2 | 39.55 percentage of ejection fraction STANDARD_DEVIATION 10 |
| Long acting nitrate users | 1 Participants | 1 Participants | 2 Participants |
| Mineralocorticoid Receptor Antagonists (MRA) users | 17 Participants | 13 Participants | 30 Participants |
| number of current tobacco users | 1 Participants | 1 Participants | 2 Participants |
| Number of Digoxin users | 5 Participants | 6 Participants | 11 Participants |
| Participants with Atrial fibrillation | 12 Participants | 9 Participants | 21 Participants |
| Participants with Diabetes mellitus | 4 Participants | 11 Participants | 15 Participants |
| Participants with Ischemic etiology | 6 Participants | 8 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 23 Participants | 47 Participants |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 17 Participants | 21 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 24 | 0 / 24 |
| other Total, other adverse events | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Number of Participants With 4 Fold Rise in Serum Antibody Concentration of A/H1N1 Vaccine Antigens
Time frame: 4 weeks
Population: 1 participant from 'standard dose influenza vaccine' arm and 1 participant from 'high dose influenza vaccine' arm were excluded as the sample was inadequate to run the assay.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dose Influenza Vaccine | Number of Participants With 4 Fold Rise in Serum Antibody Concentration of A/H1N1 Vaccine Antigens | 11 Participants |
| High Dose Influenza Vaccine | Number of Participants With 4 Fold Rise in Serum Antibody Concentration of A/H1N1 Vaccine Antigens | 12 Participants |
p-value: 0.89Chi-squared
Primary
Number of Participants With 4 Fold Rise in Serum Antibody Concentration of A/H3N2 Vaccine Antigens
Time frame: 4 weeks
Population: 1 participant from 'standard dose influenza vaccine' arm and 1 participant from 'high dose influenza vaccine' arm were excluded as the sample was inadequate to run the assay.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dose Influenza Vaccine | Number of Participants With 4 Fold Rise in Serum Antibody Concentration of A/H3N2 Vaccine Antigens | 15 Participants |
| High Dose Influenza Vaccine | Number of Participants With 4 Fold Rise in Serum Antibody Concentration of A/H3N2 Vaccine Antigens | 17 Participants |
p-value: 0.43Chi-squared
Primary
Number of Participants With 4 Fold Rise in Serum Antibody Concentration of B-type Vaccine Antigens
Time frame: 4 weeks
Population: 1 participant from 'standard dose influenza vaccine' arm and 1 participant from 'high dose influenza vaccine' arm were excluded as the sample was inadequate to run the assay.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dose Influenza Vaccine | Number of Participants With 4 Fold Rise in Serum Antibody Concentration of B-type Vaccine Antigens | 7 Participants |
| High Dose Influenza Vaccine | Number of Participants With 4 Fold Rise in Serum Antibody Concentration of B-type Vaccine Antigens | 14 Participants |
p-value: 0.03Chi-squared
Secondary
Number of All-cause Hospitalizations
All-cause hospitalizations are not considered adverse events.
Time frame: 8 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Dose Influenza Vaccine | Number of All-cause Hospitalizations | 15 hospitalizations |
| High Dose Influenza Vaccine | Number of All-cause Hospitalizations | 6 hospitalizations |
p-value: 0.01Chi-squared
Secondary
Number of Participants With Influenza Like Illness
Influenza Like Illness is not considered adverse event.
Time frame: 8 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dose Influenza Vaccine | Number of Participants With Influenza Like Illness | 8 Participants |
| High Dose Influenza Vaccine | Number of Participants With Influenza Like Illness | 7 Participants |
p-value: 0.76Chi-squared