title: 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.
abstract: BACKGROUND
  Despite administration of annual influenza vaccination, influenza-associated complications in transplant recipients continue to be an important cause of hospitalization and death. Although influenza vaccination has been proven to be the most effective measure to reduce influenza infection after transplantation, transplant recipients are still vulnerable to influenza infections, with lower serological responses to vaccination compared to the general population. In order to assess the efficacy and safety of an alternative immunization scheme for solid organ transplant recipients, the TRANSGRIPE1-2 Study Group aimed to test a booster dose administration 5 weeks after the standard vaccination. The primary objective of this trial was to compare short-term and long-term neutralizing antibody immunogenicity of a booster dose of influenza vaccination to the standard single-dose immunization scheme. Secondary objectives included the evaluation of the efficacy and/or safety, cellular immune response, incidence of influenza infection, graft rejection, retransplant and mortality rates.
  
  
  METHODS
  This phase III, randomized, controlled, open-label clinical trial was conducted between October 2012 and December 2013 in 12 Spanish public referral hospitals. Solid organ transplant recipients (liver, kidney, heart or lung), older than 16 years of age more than 30 days after transplantation were eligible to participate. Patients (N = 514) were stratified 1:1 by center, type of organ and time after transplantation and who either received the standard single dose (n = 257) or were treated according to a novel influenza vaccination schedule comprising the administration of a booster dose 5 weeks after standard vaccination (n = 254). Seroconversion rates were measured as a determinant of protection against influenza (main outcome). Efficacy and safety outcomes were followed until 1 year after influenza vaccination with assessment of short-term (0, 5, 10 and 15 weeks) and long-term (12 months) results. Intention-to-treat, per-protocol and safety analyses will be performed.
  
  
  CONCLUSIONS
  This trial will increase knowledge about the safety and efficacy of a booster dose of influenza vaccine in solid organ transplant recipients. At the time the manuscript was submitted for publication, trial recruitment was closed with a total of 499 participants included during a 2-month period (within the seasonal influenza vaccination campaign).
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT01761435 (registered 13 December 2012). EudraCT Identifier: 2011-003243-21 (registered 4 July 2011).
authors.affiliation: Hospital Universitario Virgen del Rocío and Biomedicine Research Institute (IBIS), Infectious Diseases Research Group, Avda, Manuel Siurot, s/n, 41013 Seville, Spain. jumarati@gmail.com.
authors.forename: Juliana
authors.initials: J
authors.lastname: Martinez-Atienza
authors.forename: Clara
authors.initials: C
authors.lastname: Rosso-Fernández
authors.forename: Cristina
authors.initials: C
authors.lastname: Roca
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Aydillo
authors.forename: Joan
authors.initials: J
authors.lastname: Gavaldà
authors.forename: Asunción
authors.initials: A
authors.lastname: Moreno
authors.forename: Jose M
authors.initials: JM
authors.lastname: Montejo
authors.forename: Julian
authors.initials: J
authors.lastname: Torre-Cisneros
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Fariñas
authors.forename: Jesus
authors.initials: J
authors.lastname: Fortun
authors.forename: Nuria
authors.initials: N
authors.lastname: Sabé
authors.forename: Patricia
authors.initials: P
authors.lastname: Muñoz
authors.forename: Marino
authors.initials: M
authors.lastname: Blanes-Julia
authors.forename: Alejandro
authors.initials: A
authors.lastname: Suárez-Benjumea
authors.forename: Francisco
authors.initials: F
authors.lastname: López-Medrano
authors.forename: Pilar
authors.initials: P
authors.lastname: Pérez-Romero
authors.forename: Elisa
authors.initials: E
authors.lastname: Cordero
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006085:Graft Survival; D006779:Hospitals, Public; D006801:Humans; D007117:Immunization, Secondary; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D007251:Influenza, Human / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D016377:Organ Transplantation / Q000009:adverse effects* / Q000401:mortality; D009975:Orthomyxoviridae / Q000276:immunology*; D012107:Research Design; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015415:Biomarkers; D007252:Influenza Vaccines