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

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

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

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.

Drug: Influenza vaccine (split virion, inactivated) suspension for injection 0.5ml at the baseline and 5 weeks after the first one.

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.

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).

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).

Occurrence of grade 3 or 4 toxicity, death, hospitalization, retransplantation, acute rejection and chronic rejection

Detection of clinical cases of influenza following immunization. Nasal swabs to confirm infection with influenza virus by RT-PCR (Reverse transcription polymerase chain reaction).

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.

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.

Clinical severity (hospitalization, ICU admission, death, rejection). Time to clinical stability will be register.

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).

Demetz G, Laux M, Scherhag A, Hoekstra T, Suttorp MM, Dekker F, Roest M, Marcus-Kalish M, Mittelman M, Ott I. The influence of Erythropoietin on platelet activation, thrombin generation and FVII/active FVII in patients with AMI. Thromb J. 2014 Aug 28;12:18. doi: 10.1186/1477-9560-12-18. eCollection 2014.

Martinez-Atienza J, Rosso-Fernandez C, Roca C, Aydillo TA, Gavalda J, Moreno A, Montejo JM, Torre-Cisneros J, Farinas MC, Fortun J, Sabe N, Munoz P, Blanes-Julia M, Suarez-Benjumea A, Lopez-Medrano F, Perez-Romero P, Cordero E; TRANSGRIPE 1-2 Study Group. Efficacy and safety of a booster dose of influenza vaccination in solid organ transplant recipients, TRANSGRIPE 1-2: study protocol for a multicenter, randomized, controlled clinical trial. Trials. 2014 Aug 28;15:338. doi: 10.1186/1745-6215-15-338.