Influenza Vaccination in Immunocompromized Patients

Double Blind Randomized Comparison of a Subunit- and a Virosomal Influenza Vaccine in Immunocom-Promized Patients

Evaluation of the immunogenicity and reactogenicity of two different formulations of commercially avail-able influenza vaccines in 4 different groups of immunocompromized outpatients (HIV positive patients, patients suffering from rheumatologic diseases and receiving treatment with immunosuppressive drugs and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis). The aim of the study was to investigate if the newest formulation of influenza vaccines (virosomal vaccines) offer a benefit in immunocompromized patients in comparison to an older subunit formulation.

Study Overview

• Status: Completed
• Conditions: Immunosuppression
• Intervention / Treatment: Biological: Virosomal influenza vaccine; Biological: Subunit influenza vaccine

Detailed Description

The infection with influenza is associated with higher morbidity and mortality in risk groups including immunocompromized patients. The virosomal influenza vaccines have been associated with improved immunogenicity in former trials. No direct comparison with older formulations has been conducted so far.

• Study Type: Interventional
• Enrollment (Actual): 304
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Department of Infectious Diseases, Bern University Hospital
  • Bern, Switzerland, 3010
    • Department of Nephrology/Hypertension, Bern University Hospital
  • Bern, Switzerland, 3010
    • Department of Rheumatic Diseases, Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult outpatients treated at the Inselspital Bern for:
• HIV infection
• rheumatologic diseases and receiving immunosuppressive drugs
• kidney transplant recipients
• undergoing hemodialysis or continuous ambulatory peritoneal dialysis
• written informed consent

Exclusion Criteria:

• Allergy to egg proteins
• Former adverse reactions to prior vaccination
• Febrile conditions at the time of study inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Virosomal influenza vaccine	Biological: Virosomal influenza vaccine; Influvacplus 2005/2006, Solvay Pharma AG, Bern, Switzerland Assigned to all 4 groups if immunocompromized patients
ACTIVE_COMPARATOR: Subunit influenza vaccine	Biological: Subunit influenza vaccine; Influvac 2005/2006, Solvay Pharma AG, Bern, Switzerland Assigned to all 4 groups if immunocompromized patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Immunogenicity defined as seroconversion (1:>=4) and seroprotection rates (1:>=40)	>60 Wochen

Secondary Outcome Measures

Outcome Measure	Time Frame
Reactogenicity in rheumatologic patients by disease specific scores	Six weeks after vaccination
Immediate side effects at time of application of vaccination	Minutes after vaccination
Side effects after vaccination	First week after vaccination

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Merck Sharp & Dohme LLC; Boehringer Ingelheim; Abbott; Solvay Pharmaceuticals
• Investigators: Principal Investigator: John M Evison, MD, Department of Infectious Diseases, University Hospital Bern, 3010-Bern, Switzerland

Publications and helpful links

General Publications

• Vilchez RA, Fung J, Kusne S. The pathogenesis and management of influenza virus infection in organ transplant recipients. Transpl Infect Dis. 2002 Dec;4(4):177-82. doi: 10.1034/j.1399-3062.2002.t01-4-02001.x.
• Bridges CB, Fukuda K, Cox NJ, Singleton JA; Advisory Committee on Immunization Practices. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2001 Apr 20;50(RR-4):1-44.
• Kroon FP, van Dissel JT, de Jong JC, van Furth R. Antibody response to influenza, tetanus and pneumococcal vaccines in HIV-seropositive individuals in relation to the number of CD4+ lymphocytes. AIDS. 1994 Apr;8(4):469-76. doi: 10.1097/00002030-199404000-00008.
• Dorrell L, Hassan I, Marshall S, Chakraverty P, Ong E. Clinical and serological responses to an inactivated influenza vaccine in adults with HIV infection, diabetes, obstructive airways disease, elderly adults and healthy volunteers. Int J STD AIDS. 1997 Dec;8(12):776-9. doi: 10.1258/0956462971919264.
• Chalmers A, Scheifele D, Patterson C, Williams D, Weber J, Shuckett R, Teufel A. Immunization of patients with rheumatoid arthritis against influenza: a study of vaccine safety and immunogenicity. J Rheumatol. 1994 Jul;21(7):1203-6.
• Abu-Shakra M, Press J, Varsano N, Levy V, Mendelson E, Sukenik S, Buskila D. Specific antibody response after influenza immunization in systemic lupus erythematosus. J Rheumatol. 2002 Dec;29(12):2555-7.
• Cavdar C, Sayan M, Sifil A, Artuk C, Yilmaz N, Bahar H, Camsari T. The comparison of antibody response to influenza vaccination in continuous ambulatory peritoneal dialysis, hemodialysis and renal transplantation patients. Scand J Urol Nephrol. 2003;37(1):71-6. doi: 10.1080/00365590310008749.
• Conne P, Gauthey L, Vernet P, Althaus B, Que JU, Finkel B, Gluck R, Cryz SJ Jr. Immunogenicity of trivalent subunit versus virosome-formulated influenza vaccines in geriatric patients. Vaccine. 1997 Oct;15(15):1675-9. doi: 10.1016/s0264-410x(97)00087-x.
• Baldo V, Menegon T, Bonello C, Floreani A, Trivello R; Collaborative Group. Comparison of three different influenza vaccines in institutionalised elderly. Vaccine. 2001 May 14;19(25-26):3472-5. doi: 10.1016/s0264-410x(01)00060-3.
• Zanetti AR, Amendola A, Besana S, Boschini A, Tanzi E. Safety and immunogenicity of influenza vaccination in individuals infected with HIV. Vaccine. 2002 Dec 20;20 Suppl 5:B29-32. doi: 10.1016/s0264-410x(02)00511-x.
• Evison J, Farese S, Seitz M, Uehlinger DE, Furrer H, Muhlemann K. Randomized, double-blind comparative trial of subunit and virosomal influenza vaccines for immunocompromised patients. Clin Infect Dis. 2009 May 15;48(10):1402-12. doi: 10.1086/598193.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (ACTUAL): July 1, 2006
• Study Completion (ACTUAL): March 1, 2008

Study Registration Dates

• First Submitted: October 30, 2008
• First Submitted That Met QC Criteria: October 30, 2008
• First Posted (ESTIMATE): October 31, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): November 2, 2008
• Last Update Submitted That Met QC Criteria: October 31, 2008
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: Immunogenicity; Reactogenicity; HIV/AIDS; Kidney transplantation; Renal Dialysis; Influenza vaccination; Subunit; Virosomal; Rheumatologic diseases
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: KEK No 805 (EK 151/03)