Intradermal Versus Intramuscular Trivalent Influenza Vaccine in Adult Lung Transplant Recipients

Study Overview
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Brief Summary
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The influenza virus, commonly called the flu, is a common source of infection in lung transplant patients and can often lead to pneumonia and possibly rejection. The annual influenza vaccine is the most important strategy used to prevent infection but it is not effective in all lung transplant patients. It has been thought that the response to the vaccine may be improved if it is given into the skin (intradermal) rather than the muscle (intramuscular). We hypothesize that a significantly greater proportion of patients will respond to vaccination using the intradermal influenza vaccine compared to the intramuscular vaccine.

Detailed Description
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The annual influenza vaccine is suggested for immunocompromised patients. However, the immunogenic response to this vaccine is suboptimal and ranges from 15-70%. In lung transplant recipients, responses to the influenza vaccine are poorest of all organ transplant groups. For example, a study with 43 stable lung transplant recipients showed that protective antibody developed in 19%, 30%, and 40% for the three antigens in the vaccine (only 8.6% of subjects developed protective antibody levels against all three). Similarly, 43% responded after a single dose of vaccine was given to 68 lung transplant recipients; response was significantly lower in those on mycophenolate mofetil (MMF). We have recently published a study in 60 lung transplant recipients where the standard influenza vaccine was immunogenic to at least one vaccine antigen in approximately 60% of the patients. The study we propose is a prospective randomized control trial designed to assess the immunogenicity of the influenza vaccine given intradermally compared to the standard intramuscular vaccine in lung transplant recipients. Lung transplant recipients are unique in that their vaccine responses are the lowest of all organ groups and they stand to benefit most from an alternate vaccine strategy. CLINICAL SIGNIFICANCE OF THE STUDY Lung transplant recipients appear to have one of the poorest humoral responses to influenza vaccination of all the organ transplant groups. However, influenza remains an important cause of morbidity in this population in whom protection is imperative. The current vaccine is suboptimal and newer strategies need to be studied to increase response rates. This subject area is of critical importance to study and especially in light of the threat of pandemic influenza. OBJECTIVE AND HYPOTHESIS To test the specific humoral and cellular response after the intradermal influenza vaccine. To test the safety of the intradermal influenza vaccine in the lung transplant population. We hypothesize that a significantly greater proportion of patients will respond to vaccination using the intradermal influenza vaccine compared to the intramuscular vaccine.

Official Title
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A Randomized, Controlled Trial Comparing Intradermal Versus Intramuscular Trivalent Influenza Vaccine in Adult Lung Transplant Recipients

Conditions
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Influenza Virus, Influenza Vaccine

Intervention / Treatment
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* Biological: Vaxigrip (Aventis-Pasteur Canada)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 Greater than 3 months post-transplant Outpatient status Exclusion Criteria: Has already received influenza vaccination for 2008-2009 season Egg allergy Previous life-threatening reaction to influenza vaccine (i.e. Guillain Barre Syndrome) On anticoagulants such as warfarin that precludes intramuscular injection Ongoing therapy for rejection Febrile illness in the past two weeks Unable to provide informed consent Unable to comply with study protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: intradermal<br> | Biological: Vaxigrip (Aventis-Pasteur Canada)<br>* The intramuscular dose (0.5 mL contains 15 micrograms antigen from each strain and the intradermal doses (2 x 0.1 mL)contain 6 micrograms antigen from each strain.<br>* Other names: Influenza vaccine;|
| Active Comparator: intramuscular<br> | Biological: Vaxigrip (Aventis-Pasteur Canada)<br>* The intramuscular dose (0.5 mL contains 15 micrograms antigen from each strain and the intradermal doses (2 x 0.1 mL)contain 6 micrograms antigen from each strain.<br>* Other names: Influenza vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate: serological response with a four-fold or greater increase in HI antibody titers Seroprotection rate: HIA titers of >/= 1:40 |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local and systemic adverse events to vaccination |  | 24 hours, 48 hours and 7 days after each vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung transplant Recipients, Vaxigrip