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

• ClinicalTrials.gov Identifier: NCT01761435
• Recruitment Status: Completed
• First Posted: January 4, 2013
• Last Update Posted: May 1, 2015
• Sponsor: Fundación Pública Andaluza Progreso y Salud
• Collaborator: Spanish Network for Research in Infectious Diseases
• Information provided by (Responsible Party): Andalusian Network for Design and Translation of Advanced Therapies ( Fundación Pública Andaluza Progreso y Salud )

Tracking Information

• First Submitted Date: December 13, 2012
• First Posted Date: January 4, 2013
• Last Update Posted Date: May 1, 2015
• Study Start Date: October 2012
• Actual Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 3, 2013)

Seroconversion rates [ Time Frame: At 5, 10, 15 weeks, and 12 months after the first vaccine dose ]

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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 3, 2013)

• Postvaccination antibody titers [ Time Frame: At 5, 10, 15 weeks, and 12 months after the first vaccine dose. ]
  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).
• Safety. [ Time Frame: At 5, 10, 15 weeks, and 12 months after the first vaccine dose ]
  Occurrence of grade 3 or 4 toxicity, death, hospitalization, retransplantation, acute rejection and chronic rejection
• Efficacy [ Time Frame: At 5, 10, 15 weeks, and 12 months after the first vaccine dose ]
  Detection of clinical cases of influenza following immunization. Nasal swabs to confirm infection with influenza virus by RT-PCR (Reverse transcription polymerase chain reaction).
• Antibody anti-HLA [ Time Frame: At 5, 10, 15 weeks, and 12 months after the first vaccine dose ]
  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.
• Cellular response [ Time Frame: At 5, 10, 15 weeks, and 12 months after the first vaccine dose ]
  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 complications [ Time Frame: At 5, 10, 15 weeks, and 12 months after the first vaccine dose ]
  Clinical severity (hospitalization, ICU admission, death, rejection). Time to clinical stability will be register.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Trial Evaluating Efficacy and Safety of One Dose Versus Two Doses of Influenza Vaccination
• Official Title: 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
• Brief Summary: 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

The purposes of this study are:

1. Evaluate the efficacy and safety of a double dose of seasonal flu vaccine compared to a single dose.
2. 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).
3. Evaluate the humoral immune response produced after one dose vs two doses of seasonal flu vaccine by the measure of serum antibody levels.
4. Evaluate clinical efficacy of stationary flu vaccine in solid organ transplant recipients.
5. Evaluate a long term cellular and humoral response(1 year) of seasonal flu vaccine.
6. Characterize the genetic expression profile of immune response after the flu vaccine in solid organ transplant recipients by means of a genetic sub-study.
7. 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Infection in Solid Organ Transplant Recipients

Intervention

Biological: Influenza vaccine

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.

Study Arms

• Experimental: Influenza vaccine, second administration after 5 weeks
  Drug: Influenza vaccine (split virion, inactivated) suspension for injection 0.5ml at the baseline and 5 weeks after the first one.
  Intervention: Biological: Influenza vaccine
• Active Comparator: Influenza vaccine
  Drug: Influenza vaccine (split virion, inactivated) suspension for injection 0.5ml at the baseline.
  Intervention: Biological: Influenza vaccine

Publications *

• 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-Fernández C, Roca C, Aydillo TA, Gavaldà J, Moreno A, Montejo JM, Torre-Cisneros J, Fariñas MC, Fortun J, Sabé N, Muñoz P, Blanes-Julia M, Suárez-Benjumea A, López-Medrano F, Pérez-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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 4, 2013): 499
• Original Estimated Enrollment (submitted: January 3, 2013): 508
• Actual Study Completion Date: January 2014
• Actual Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Solid organ transplant recipient.
2. 16 years or older.
3. More than 30 days after transplantation.
4. Negative pregnancy test for women of childbearing potential
5. The patient must give informed consent

Exclusion Criteria:

1. No written informed consent.
2. Acute rejection within 15 days prior to vaccination.
3. Pregnancy.
4. Hypersensitivity to the active substance, any of the excipients and waste, for example: eggs, egg albumin, chicken proteins.
5. History of a previous serious reaction to immunization (eg Guillain-Barré syndrome).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT01761435
• Other Study ID Numbers: TraNsgripe1-2
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Andalusian Network for Design and Translation of Advanced Therapies ( Fundación Pública Andaluza Progreso y Salud )
• Study Sponsor: Fundación Pública Andaluza Progreso y Salud
• Collaborators: Spanish Network for Research in Infectious Diseases

Investigators

• Principal Investigator: Julian De la Torre Cisneros, PhD; COMPLEJO HOSPITALARIO REGIONAL REINA SOFÍA
• Principal Investigator: Francisco López Medrano, PhD; Hospital Universitario 12 de Octubre
• Principal Investigator: Patricia Muñoz García, PhD; HOSPITAL GENERAL GREGORIO MARAÑÓN
• Principal Investigator: Jesús Fortun Abete, PhD; Hospital Universitario Ramon y Cajal
• Principal Investigator: Joán Gavaldà Santapau, PhD; HOSPITALS VALL D'HEBRON
• Principal Investigator: Jordi Carratalá Fernández, PhD; Hospital Universitari de Bellvitge
• Principal Investigator: Asunción Moreno Camacho, PhD; Hospital Clinic i provincial de Barcelona
• Principal Investigator: José Miguel Montejo Baranda, PhD; HOSPITAL UNIVERSITARIO DE CRUCES
• Principal Investigator: Marino Blanes Julia, PhD; Hospital Universitario La Fe
• Principal Investigator: Alejandro Suarez Benjumea, PhD; COMPLEJO HOSPITALARIO REGIONAL VIRGEN MACARENA
• Principal Investigator: Carmen Fariñas Álvarez, PhD; Hospital Universitario Marqués de Valdecilla
• Principal Investigator: Maria Elisa Cordero Matia, PhD; HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO

• PRS Account: Andalusian Network for Design and Translation of Advanced Therapies
• Verification Date: April 2015