Clinical Trial Evaluating Efficacy and Safety of One Dose Versus Two Doses of Influenza Vaccination

Study Overview
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Brief Summary
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Randomized, multicenter, open label trial to compare safety and efficacy of two doses stationary flu vaccination vs one doses in Solid Organ Transplant Recipients.

Detailed Description
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The purposes of this study are: Evaluate the efficacy and safety of a double dose of seasonal flu vaccine compared to a single dose. Determine the specific cellular immune response produced after the first and second vaccine doses of seasonal flu vaccine by in vitro stimulation of specific memory cells (A and B flu viruses). Evaluate the humoral immune response produced after one dose vs two doses of seasonal flu vaccine by the measure of serum antibody levels. Evaluate clinical efficacy of stationary flu vaccine in solid organ transplant recipients. Evaluate a long term cellular and humoral response(1 year) of seasonal flu vaccine. Characterize the genetic expression profile of immune response after the flu vaccine in solid organ transplant recipients by means of a genetic sub-study. Characterize the flu vaccine effect (one dose and two doses) through the antibody anti-HLA(human leukocyte antigen), and its influence on the rejection rate in solid organ transplant recipients, by means of immunologic sub-study.

Official Title
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Randomized, Comparative and Prospective Clinical Trial Evaluating Efficacy and Safety of a Dose of Seasonal Flu Vaccine Compared to Two Doses of Vaccine for Prevention of Influenza in Solid Organ Transplant Recipients

Conditions
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Infection in Solid Organ Transplant Recipients

Intervention / Treatment
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* Biological: Influenza vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Solid organ transplant recipient. 16 years or older. More than 30 days after transplantation. Negative pregnancy test for women of childbearing potential The patient must give informed consent Exclusion Criteria: No written informed consent. Acute rejection within 15 days prior to vaccination. Pregnancy. Hypersensitivity to the active substance, any of the excipients and waste, for example: eggs, egg albumin, chicken proteins. History of a previous serious reaction to immunization (eg Guillain-Barré syndrome).

Ages Eligible for Study
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Minimum Age: 16 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Influenza vaccine, second administration after 5 weeks<br>Drug: Influenza vaccine (split virion, inactivated) suspension for injection 0.5ml at the baseline and 5 weeks after the first one. | Biological: Influenza vaccine<br>* Patients will be randomized at 1:1 rate and open label fashion, according to centers, and time elapsed since transplant and type of organ transplanted to one of this two interventions : A arm (usual treatment): Influenza vaccine (split virion, inactivated) suspension for injection 0.5ml at the baseline. B arm (experimental branch): Influenza vaccine (split virion, inactivated) suspension for injection 0.5ml at the baseline and 5 weeks after the first dose. The follow-up of both arms will be at 5, 10 and 15 weeks and one year after the baseline.<br>|
| Active Comparator: Influenza vaccine<br>Drug: Influenza vaccine (split virion, inactivated) suspension for injection 0.5ml at the baseline. | Biological: Influenza vaccine<br>* Patients will be randomized at 1:1 rate and open label fashion, according to centers, and time elapsed since transplant and type of organ transplanted to one of this two interventions : A arm (usual treatment): Influenza vaccine (split virion, inactivated) suspension for injection 0.5ml at the baseline. B arm (experimental branch): Influenza vaccine (split virion, inactivated) suspension for injection 0.5ml at the baseline and 5 weeks after the first dose. The follow-up of both arms will be at 5, 10 and 15 weeks and one year after the baseline.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rates | Difference in seroconversion rates in both treatment groups at 5, 10, 15 weeks, and 12 months after the first vaccine dose (percent of patients with 4 x increase in the pre-vaccination titers). | At 5, 10, 15 weeks, and 12 months after the first vaccine dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postvaccination antibody titers | Geometric average postvaccination antibody titers and rate of increase between pre-and post-vaccination geometric mean, post-vaccination seroprotection rate (or percentage of individuals with a titer 1 / 40 as measured by RIH). | At 5, 10, 15 weeks, and 12 months after the first vaccine dose. | 
| Safety. | Occurrence of grade 3 or 4 toxicity, death, hospitalization, retransplantation, acute rejection and chronic rejection | At 5, 10, 15 weeks, and 12 months after the first vaccine dose | 
| Efficacy | Detection of clinical cases of influenza following immunization. Nasal swabs to confirm infection with influenza virus by RT-PCR (Reverse transcription polymerase chain reaction). | At 5, 10, 15 weeks, and 12 months after the first vaccine dose | 
| Antibody anti-HLA | Characterize the flu vaccine effect (one dose and two doses) through the antibody anti-HLA levels, ant its influence on the rejection rate in solid organ transplant recipients, by means of immunologic sub-study. | At 5, 10, 15 weeks, and 12 months after the first vaccine dose | 
| Cellular response | Determination of the T cells specific immune response measured by production of INFg, IL-2 and IL-4 in the cytoplasm of CD4+ and CD8 + (mononuclear cells) specific for influenza virus by direct immunofluorescence and flow cytometry analysis. | At 5, 10, 15 weeks, and 12 months after the first vaccine dose | 
| Clinical complications | Clinical severity (hospitalization, ICU admission, death, rejection). Time to clinical stability will be register. | At 5, 10, 15 weeks, and 12 months after the first vaccine dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Solid Organ Transplant Recipients