Influenza, Human, Transplantation Infection
Conditions
Keywords
kidney transplant, heart transplant, lung transplant, influenza vaccine
Brief summary
Influenza infection in recipients of solid organ transplants recipients while on maintenance immunosuppressant therapy is associated with increased morbidity and mortality. Although influenza vaccination is recommended in these high-risk patients, safety and immunogenicity of commercially available different strengths of influenza vaccine have not been established. The primary study objective is to determine the safety and immunogenicity of Fluzone and Fluzone High-Dose, with a secondary objective to determine the tolerability and efficacy of two different strengths of trivalent influenza vaccine (TIV, flu vaccine). Both vaccines are commercially available for use in the general population. Fluzone is approved for use in 6 months of age and older, and Fluzone High-Dose is approved for use in 65 years of age and older. This is an exploratory, open-label, parallel group, observer blinded, prospective study. All recipients of kidney, lung, heart transplants who attend for post-transplant follow-up, at least 30-days after transplantation at Inova Fairfax Hospital Transplant Center will be eligible for enrollment. Enrolled patients will be followed for three months (a total of 4 visits) following enrollment and randomization: day 0 (enrollment) and follow-up visits at weeks 1, 4, 8, and 12.
Detailed description
A potential strategy to enhance immune responses to influenza vaccine in this patient population could be to use different strengths of TIV. One of the pathways that can improve the immunogenicity of inactivated vaccines is to increase the dose of influenza antigens contained in the vaccine. Studies have demonstrated that increasing the dose of the influenza virus hemagglutinin for each of the commonly encountered viral strains beyond the conventional dose of 15 microgram for each strain is associated with dose-dependent increase in serum antibody titers. Influenza TIV is commercially available in two different strengths, Fluzone as well as Fluzone High-Dose, and it is valuable because of variable immunogenic potency of different strengths. Fluzone is approved for use in persons 6 months of age and older. High-dose Fluzone is approved for use in persons 65 years of age and older. The purpose of this exploratory study is to assess the safety, tolerability, and immunogenicity of these two commercially available different strengths of TIV in solid organ transplant recipients (kidney, heart and lung) in the period after 30 days after transplant procedure. We will evaluate the safety, tolerability (reactogenicity) and immunogenicity of two different strengths of commercially available TIV in a single center, cluster randomization, investigator blinded, study by enrolling patients in the post-transplant clinic at Inova Fairfax Hospital from: August 1, 2013 - March 31, 2014; and August 1, 2014 to March 31, 2015. Study protocol will remain active till December 31, 2016. All bio-specimens will be stored till December 31, 2016.
Interventions
BIOLOGICALinfluenza trivalent inactive vaccine
one time IM injection of standard influenza vaccine to measure immunogenicity, safety, and efficacy in organ transplant recipients
BIOLOGICALinfluenza trivalent inactive vaccine high dose
one time IM injection of high dose influenza vaccine to measure immunogenicity, safety, and efficacy in organ transplant recipients
Sponsors
Inova Health Care Services
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. All adults age ≥18 years of age following solid organ transplants (kidney, heart and lung) of all races and gender unless as specified in the
Exclusion criteria
. 2. At least 30 days after organ transplantation of kidney, heart, or lung. 3. In good health as determined by a) medical history, b) physical examinations, c) clinical judgment of the investigator team. 4. Informed consent will be obtained from all the subjects before enrollment into the study, after the nature of the study has been fully explained to the satisfaction of the participant. 5. Non-English speaking persons will be included ONLY if consent can be obtained with the help of the translator or interpreter.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Local Site Reactions | Day 1 and weeks 1, 4, and 12 | Evaluation of local and systemic reactions, use of analgesics or antipyretics. |
| Measurement of Strain-specific Hemagglutination Inhibition (HI) Antibody Titers | Week 1, 4, and 12 | Number of patients and percentage of subjects achieving hemagglutination inhibition (HI) titer≥40 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Cause ED Visits/Unscheduled Clinic Visits | day 1 - 3 months | All-cause outpatient/Emergency department visits during study follow-up (other than pre-specified post transplant follow-up visits). |
| Number and Percentage of Subjects in Each Group Achieving Seroconversion for Each Strain | Week 4 and Week 12 | Number and percentage of subjects in each group achieving seroconversion (at least 4-fold increase in titers from baseline) for each any strain at weeks 4 and 12 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SD-IIV3 Standard-dose trivalent (SD-IIV3) seasonal influenza vaccine | 30 |
| HD-IIV3 high-dose trivalent (HD-IIV3) seasonal influenza vaccine | 32 |
| Total | 62 |
Baseline characteristics
| Characteristic | HD-IIV3 | SD-IIV3 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 3 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 27 Participants | 53 Participants |
| Age, Continuous | 56.6 years | 54.9 years | 55.7 years |
| Region of Enrollment United States | 32 Participants | 30 Participants | 62 Participants |
| Sex: Female, Male Female | 13 Participants | 7 Participants | 20 Participants |
| Sex: Female, Male Male | 19 Participants | 23 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 32 |
| other Total, other adverse events | 13 / 30 | 14 / 32 |
| serious Total, serious adverse events | 0 / 30 | 0 / 32 |
Outcome results
Primary
Measurement of Strain-specific Hemagglutination Inhibition (HI) Antibody Titers
Number of patients and percentage of subjects achieving hemagglutination inhibition (HI) titer≥40
Time frame: Week 1, 4, and 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose Flu Vaccine | Measurement of Strain-specific Hemagglutination Inhibition (HI) Antibody Titers | week 1 | 14 Participants |
| High Dose Flu Vaccine | Measurement of Strain-specific Hemagglutination Inhibition (HI) Antibody Titers | Week 4 | 16 Participants |
| High Dose Flu Vaccine | Measurement of Strain-specific Hemagglutination Inhibition (HI) Antibody Titers | Week 12 | 15 Participants |
| Flu Vaccine | Measurement of Strain-specific Hemagglutination Inhibition (HI) Antibody Titers | week 1 | 19 Participants |
| Flu Vaccine | Measurement of Strain-specific Hemagglutination Inhibition (HI) Antibody Titers | Week 4 | 23 Participants |
| Flu Vaccine | Measurement of Strain-specific Hemagglutination Inhibition (HI) Antibody Titers | Week 12 | 21 Participants |
Primary
Number of Patients With Local Site Reactions
Evaluation of local and systemic reactions, use of analgesics or antipyretics.
Time frame: Day 1 and weeks 1, 4, and 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose Flu Vaccine | Number of Patients With Local Site Reactions | 2 Participants |
| Flu Vaccine | Number of Patients With Local Site Reactions | 2 Participants |
Secondary
All Cause ED Visits/Unscheduled Clinic Visits
All-cause outpatient/Emergency department visits during study follow-up (other than pre-specified post transplant follow-up visits).
Time frame: day 1 - 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose Flu Vaccine | All Cause ED Visits/Unscheduled Clinic Visits | 30 Participants |
| Flu Vaccine | All Cause ED Visits/Unscheduled Clinic Visits | 25 Participants |
Secondary
Number and Percentage of Subjects in Each Group Achieving Seroconversion for Each Strain
Number and percentage of subjects in each group achieving seroconversion (at least 4-fold increase in titers from baseline) for each any strain at weeks 4 and 12
Time frame: Week 4 and Week 12
Population: Analysis performed only for participants between ages of 18 and 65.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose Flu Vaccine | Number and Percentage of Subjects in Each Group Achieving Seroconversion for Each Strain | week 4 | 7 Participants |
| High Dose Flu Vaccine | Number and Percentage of Subjects in Each Group Achieving Seroconversion for Each Strain | week 12 | 7 Participants |
| Flu Vaccine | Number and Percentage of Subjects in Each Group Achieving Seroconversion for Each Strain | week 4 | 6 Participants |
| Flu Vaccine | Number and Percentage of Subjects in Each Group Achieving Seroconversion for Each Strain | week 12 | 7 Participants |