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

Phase 3
Completed
Conditions
Infection in Solid Organ Transplant Recipients
Interventions
Biological: Influenza vaccine
Registration Number
NCT01761435
Lead Sponsor
Fundación Pública Andaluza Progreso y Salud
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
499
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Influenza vaccineInfluenza vaccineDrug: Influenza vaccine (split virion, inactivated) suspension for injection 0.5ml at the baseline.
Influenza vaccine, second administration after 5 weeksInfluenza vaccineDrug: Influenza vaccine (split virion, inactivated) suspension for injection 0.5ml at the baseline and 5 weeks after the first one.
Primary Outcome Measures
NameTimeMethod
Seroconversion ratesAt 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
NameTimeMethod
Cellular responseAt 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.

Postvaccination antibody titersAt 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).

Antibody anti-HLAAt 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.

EfficacyAt 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).

Safety.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

Clinical complicationsAt 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.

Trial Locations

Locations (12)

Hospital General Gregorio Marañon

🇪🇸

Madrid, Spain

Hospital Ramón y Cajal

🇪🇸

Madrid, Spain

Hospital Clinic Provincial de Barcelona

🇪🇸

Barcelona, Spain

Hospital Universitario de Cruces

🇪🇸

Bilbao, Spain

Hospital Universitario Masqués de Valdecilla

🇪🇸

Santander, Bilbao, Spain

Hospital Universitario Reina Sofía

🇪🇸

Córdoba, Spain

Hospital Universitario de Bellvitge

🇪🇸

Barcelona, Spain

Hospital Universitario Virgen del Rocío

🇪🇸

Sevilla, Spain

Hospital Regional Virgen de la Macarena

🇪🇸

Sevilla, Spain

Hospital la Fe de Valencia

🇪🇸

Valencia, Spain

Hospital Universitario 12 Octubre

🇪🇸

Madrid, Spain

Hospital Vall d'Hebron

🇪🇸

Madrid, Spain

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