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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Infection in Solid Organ Transplant Recipients	Biological: Influenza vaccine	Phase 3

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	499 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
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
Study Start Date :	October 2012
Actual Primary Completion Date :	January 2014
Actual Study Completion Date :	January 2014

Arms and Interventions

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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.

Outcome Measures

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Primary Outcome Measures :

1. 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).

Secondary Outcome Measures :

1. 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).
2. 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
3. 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).
4. 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.
5. 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.
6. 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.

Eligibility Criteria

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Ages Eligible for Study:	16 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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).

Contacts and Locations

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Locations

Spain
Hospital Universitario Masqués de Valdecilla
Santander, Bilbao, Spain
Hospital Clinic Provincial de Barcelona
Barcelona, Spain
Hospital Universitario de Bellvitge
Barcelona, Spain
Hospital Universitario de Cruces
Bilbao, Spain
Hospital Universitario Reina Sofía
Córdoba, Spain
Hospital General Gregorio Marañon
Madrid, Spain
Hospital Ramón y Cajal
Madrid, Spain
Hospital Universitario 12 Octubre
Madrid, Spain
Hospital Vall d'Hebron
Madrid, Spain
Hospital Universitario Virgen del Rocío
Sevilla, Spain, 41013
Hospital Regional Virgen de la Macarena
Sevilla, Spain
Hospital la Fe de Valencia
Valencia, Spain

Sponsors and Collaborators

Fundación Pública Andaluza Progreso y Salud

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

More Information

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Additional Information:

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 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier:	NCT01761435 History of Changes
Other Study ID Numbers:	TraNsgripe1-2
First Posted:	January 4, 2013
Last Update Posted:	May 1, 2015
Last Verified:	April 2015

Keywords provided by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud ( Fundación Pública Andaluza Progreso y Salud ):

Influenza; Solid Organ Transplant Recipients

Additional relevant MeSH terms:

Influenza, Human; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections	Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs