Immunogenicity and Safety of Vaccinations in Immunocompromised Persons

This study has been completed.
Sponsor:
Collaborators:
University of Basel
Swiss Tropical & Public Health Institute
University of Bern
University Hospital, Geneva
Cantonal Hospital of St. Gallen
Cantonal Hospital of Aarau, Switzerland
Information provided by (Responsible Party):
University of Zurich
ClinicalTrials.gov Identifier:
NCT01947465
First received: August 22, 2013
Last updated: February 24, 2016
Last verified: February 2016
  Purpose

Backgound and relevance of the project:

Patients with autoimmune inflammatory rheumatic diseases (AIIRD) are at increased risk of contracting infections. The increased risk can be attributed to the immunological disorder itself, as well as to the immunosuppressive treatment. Vaccination against many infections is recommended in this patient group. However, the immunogenicity of vaccines may be reduced and may also be influenced by the administered treatment. Potential reactivation of the underlying disease triggered by vaccination is another important concern.

From the patients' and public health perspectives, an important task of physicians is giving advice on vaccines. Completing this task is often difficult, because data on the immunogenicity and safety of vaccines in these patient groups are scarce, especially with regard to treatment with new immunosuppressive medications, such as biological agents. Lastly and importantly, due to new therapeutic options, health among AIIRD patients has considerably improved and an increasing number of patients undertake overseas travel activities requiring additional vaccinations. In this context, reliable advice with regard to vaccinations is almost impossible, because for most travel vaccinations the immunogenicity and safety profile is unknown.

Research addressing the immunogenicity and safety of vaccines in different autoimmune inflammatory diseases treated with different immunosuppressive medications is urgently needed to allow giving evidence based vaccine advice.

In this observational study the immunogenicity and safety of tetanus booster and hepatitis A vaccinations will be assessed in AIIRD patients. The immune response will be evaluated as a function of the underlying disease and the possible influence of commonly used immunosuppressive drugs on the immune response will be studied.

Rationale for studying tetanus booster and hepatitis A vaccine Tetanus vaccination is one of the most frequently recommended vaccinations, and the effect of a booster vaccination can be addressed. Hepatitis A vaccine is the most widely used travel vaccine. Despite their importance, only very limited data are available for tetanus and hepatitis A vaccine in this patient group. By focusing on these vaccines the study will lead the way to the evaluation of further vaccines.

The purpose of this study is to determine whether tetanus and hepatitis A vaccinations are as immunogenic and safe in AIIRD patients as in healthy controls.


Condition Intervention
Arthritis, Rheumatoid
Spondylarthritis
Vasculitis
Biological: Hepatitis A vaccine and tetanus vaccine

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Prospective Cohort Study in 6 Swiss Rheumatology Centres and 4 Travel Clinics on the Immunogenicity and Safety of Tetanus and Hepatitis A Vaccine in Patients With Rheumatoid Arthritis, Axial Spondyloarthritis and Vasculitis and Healthy Controls

Resource links provided by NLM:


Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • Immunogenicity of hepatitis A and tetanus vaccination in patients with rheumatoid arthritis, axial spondyloarthritis and vasculitis and in healthy controls [ Time Frame: Change from Baseline in geometric mean antibody titre and seroprotection at 4 weeks and at 12 weeks ] [ Designated as safety issue: No ]
    comparison of the geometric mean antibody titre and percentage of seroprotected individuals after tetanus and hepatitis A vaccination between each disease group and healthy controls


Secondary Outcome Measures:
  • Safety of tetanus and hepatitis A vaccines in patients with rheumatoid arthritis, axial spondyloarthritis and vasculitis and in healthy controls [ Time Frame: Activation of rheumatic disease will be assessed for 1 week after vaccine administration and at 4 and 12 weeks compared to baseline ] [ Designated as safety issue: Yes ]

    Number of patients with any worsening or reactivation of the rheumatic disease after vaccine administration

    Number of participants with adverse vaccine reactions (local and systemic reactions) in patients with rheumatoid arthritis, axial spondyloarthritis and vasculitis and in healthy controls



Biospecimen Retention:   Samples Without DNA
Sera from participants will be kept in a biobank for further measurements of antibody responses after vaccination.

Enrollment: 645
Study Start Date: October 2013
Study Completion Date: February 2016
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Healthy controls
If a vaccination is indicated according to the recommendations by the Swiss Federal Office of Public Health: 319 healthy controls will be enrolled and will receive hepatitis A and/or tetanus vaccination
Biological: Hepatitis A vaccine and tetanus vaccine
Hepatitis A and/or tetanus vaccination will be given to participants in all group on day 0. All monovalent active hepatitis A vaccinations and all vaccines containing tetanus toxoid available in Switzerland may be used in the study
Other Names:
  • Havrix 1440
  • Epaxal
  • Td-Pur
  • Boostrix
  • BoostrixPolio
  • Revaxis
Patients with rheumatoid arthritis
If a vaccination is indicated according to the recommendations by the Swiss Federal Office of Public Health: 142 patients with rheumatoid arthritis will be enrolled and will receive hepatitis A and/or tetanus vaccination.
Biological: Hepatitis A vaccine and tetanus vaccine
Hepatitis A and/or tetanus vaccination will be given to participants in all group on day 0. All monovalent active hepatitis A vaccinations and all vaccines containing tetanus toxoid available in Switzerland may be used in the study
Other Names:
  • Havrix 1440
  • Epaxal
  • Td-Pur
  • Boostrix
  • BoostrixPolio
  • Revaxis
Patients with axial spondylarthritis
If a vaccination is indicated according to the recommendations by the Swiss Federal Office of Public Health: 142 patients with axial spondylarthritis will be enrolled and will receive hepatitis A and/or tetanus vaccination.
Biological: Hepatitis A vaccine and tetanus vaccine
Hepatitis A and/or tetanus vaccination will be given to participants in all group on day 0. All monovalent active hepatitis A vaccinations and all vaccines containing tetanus toxoid available in Switzerland may be used in the study
Other Names:
  • Havrix 1440
  • Epaxal
  • Td-Pur
  • Boostrix
  • BoostrixPolio
  • Revaxis
Patients with vasculitis
If a vaccination is indicated according to the recommendations by the Swiss Federal Office of Public Health: 142 patients with vasculitis will be enrolled and will receive hepatitis A and/or tetanus vaccination.
Biological: Hepatitis A vaccine and tetanus vaccine
Hepatitis A and/or tetanus vaccination will be given to participants in all group on day 0. All monovalent active hepatitis A vaccinations and all vaccines containing tetanus toxoid available in Switzerland may be used in the study
Other Names:
  • Havrix 1440
  • Epaxal
  • Td-Pur
  • Boostrix
  • BoostrixPolio
  • Revaxis

Detailed Description:
The study will be placed in 6 rheumatology clinics in Switzerland and in 4 travel medicine clinics. Consecutive subjects with rheumatoid arthritis, spondylarthritis (ankylosing spondylitis), vasculitis (ANCA associated vasculitis and Behçet's disease) and healthy controls will be recruited.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
The cohort will be selected from patients with rheumatic diseases under treatment at 6 rheumatology outpatient clinics in Switzerland (University of Basel, University of Bern, University of Geneva, University of Zurich, Cantonal Hospital Aarau, Cantonal Hospital St. Gallen)
Criteria

Inclusion Criteria:

  • Indication for hepatitis A and/or tetanus vaccination according to Swiss Federal Office of Public Health recommendations
  • Male and female rheumatic patients with rheumatoid arthritis or axial spondyloarthritis (ankylosing spondylitis, axial psoriatic arthritis, axial undifferentiated spondyloarthritis, enteropahtic arthritis) or peripheral psoriatic arthritis or vasculitis (Behçet's disease or ANCA-associated vasculitis) or male and female healthy participants ≥ 18 years
  • Signed Informed Consent after being informed

Exclusion Criteria:

  • Known hypersensitivity to a vaccine ingredient
  • Estimated patient survival below 1 year
  • Active malignant or active infectious disease
  • Drug/alcohol abuse
  • Insufficient understanding of local language
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01947465

Locations
Switzerland
Cantonal Hospital Aarau, Division of Rheumatology
Aarau, Aargau, Switzerland, 5001
Swiss Tropical and Public Health Institute
Basel, Basel Town, Switzerland, 4051
University Hospital of Basel, Rheumatology Division
Basel, Basel Town, Switzerland, 4031
University of Bern, Inselspital, Division of Infectious Diseases and Travel Medicine
Bern, Switzerland, 3010
University of Bern, Inselspital, Division of Rheumatology
Bern, Switzerland, 3010
University of Geneva, University Hospitals, Division of Rheumatology
Geneva, Switzerland, 1211
University of Geneva, University Hospitals, Service de Médecine Tropicale et Humanitaire
Geneva, Switzerland, 1211
Cantonal Hospital St. Gallen, Division of Rheumatology
St. Gallen, Switzerland, 9007
University of Zurich, University Hopsital, Divison of Rheumatology
Zürich, Switzerland, 8091
University of Zurich, Epidemiology, Biostatistics and Prevention Institute, Divison of Infectious Diseases
Zürich, Switzerland, 8001
Sponsors and Collaborators
University of Zurich
University of Basel
Swiss Tropical & Public Health Institute
University of Bern
University Hospital, Geneva
Cantonal Hospital of St. Gallen
Cantonal Hospital of Aarau, Switzerland
Investigators
Principal Investigator: Christoph Hatz, Professor University of Zurich, Epidemiology, Biostatistics and Prevention Institute
  More Information

Additional Information:
Publications:

Responsible Party: University of Zurich
ClinicalTrials.gov Identifier: NCT01947465     History of Changes
Other Study ID Numbers: CS_2013_01 
Study First Received: August 22, 2013
Last Updated: February 24, 2016
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Vasculitis
Spondylarthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Vascular Diseases
Cardiovascular Diseases
Spondylitis
Spinal Diseases
Bone Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 27, 2016