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.

Study Overview

• Status: Completed
• Conditions: Infection in Solid Organ Transplant Recipients
• Intervention / Treatment: Biological: Influenza vaccine

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
• Enrollment (Actual): 499
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Hospital Universitario de Bellvitge
  • Barcelona, Spain
    • Hospital Clinic Provincial De Barcelona
  • Bilbao, Spain
    • Hospital Universitario de Cruces
  • Córdoba, Spain
    • Hospital Universitario Reina Sofia
  • Madrid, Spain
    • Hospital Ramon y Cajal
  • Madrid, Spain
    • Hospital General Gregorio Marañón
  • Madrid, Spain
    • Hospital Universitario 12 Octubre
  • Madrid, Spain
    • Hospital Vall d'Hebron
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Sevilla, Spain
    • Hospital Regional Virgen de la Macarena
  • Valencia, Spain
    • Hospital La Fe de Valencia
  • Bilbao
    • Santander, Bilbao, Spain
      • Hospital Universitario Masqués de Valdecilla

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.
Active Comparator: Influenza vaccine; Drug: Influenza vaccine (split virion, inactivated) suspension for injection 0.5ml at the baseline.	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.

What is the study measuring?

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

Collaborators and Investigators

• 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

Publications and helpful links

General 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-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.

Helpful Links

• The Spanish Network for the Research in Infectious Diseases (REIPI) is based in research groups of high standards and professional level. REIPI´s aim is to generate scientific knowledge in the field of the infectious diseases, in areas ranging from basic

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: December 13, 2012
• First Submitted That Met QC Criteria: January 3, 2013
• First Posted (Estimate): January 4, 2013

Study Record Updates

• Last Update Posted (Estimate): May 1, 2015
• Last Update Submitted That Met QC Criteria: April 30, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Influenza; Solid Organ Transplant Recipients
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: TraNsgripe1-2