Clinical trial NCT01022749: Efficacy Safety Study of Flu Vaccine in Immunodepression Patients
Official title: Prospective, Multicentre, Open-label Study Evaluating the Immunogenicity and Safety of Influenza Vaccine in Patients With Inflammatory Bowel Disease (IBD) Receiving or Not Immunosuppressive Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Inflammatory Bowel Disease (IBD)
Keywords: inflammatory bowel disease (IBD)
immunosuppressed or non-immunosuppressed
influenza vaccine
antibody titers
seroprotective titers
vaccine-associated adverse events
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: University of Paris 5 - Rene Descartes
name: Pierre and Marie Curie University
name: Institut Pasteur
First posted: 2009-12-01
Enrollment: 228
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to compare the efficacy and safety of influenza vaccine in patients with inflammatory bowel disease (IBD) receiving immunosuppressive therapy with patients not receiving immunosuppressants .

The main objective of the study is to evaluate the humoral immunogenicity of influenza vaccination in patients with IBD

Detailed description: Annual vaccination against influenza is recommended for those at high risk of complications, particularly among patients with immunodeficiency including those resulting from immunosuppressive treatments administered for a chronic inflammatory bowel disease (IBD). However, published data showing that influenza vaccination coverage is low in this population (\<30%) due to lack of data on the effectiveness of vaccination in these patients and the theoretical risk of negative impact on the evolution of IBD.

To improve influenza vaccination coverage of the population treated by immunosuppressants for a chronic IBD, it is essential to have data on the effectiveness of vaccination in these populations.

The research aims to evaluate the immunogenicity of influenza vaccination in patients followed for a chronic IBD.

Factors in choice of study population were as follows:

1. IBD is a common disease. Among the inflammatory diseases treated with immunosuppressants and reaching patients under 65 years, IBD are among the most frequent. They result from an abnormal immune response to gut flora and their management often requires the prescription of immunosuppressive drugs (azathioprine, methotrexate, in particular) and more recently TNF-blockers;
2. the existence of vaccine recommendations published recently for specific patients on immunosuppressive therapy at greatest risk of complications related to influenza;
3. the fact that vaccinations have not been implicated in the pathogenesis of the disease;
4. data showing that vaccination recommendations are poorly followed in this population. A recently published work found vaccination coverage against influenza of only 28% in a cohort of 169 patients treated for IBD;

The methodology chosen is a phase III, prospective, open, vaccine trial. The primary endpoint is the humoral immunogenicity induced by the vaccine.

The study is scheduled on 2 successive years to assess the value of annual vaccination repeated in this population treated with immunosuppressants.

There is a benefit for patients to participate in this study because they are all vaccinated against influenza and will benefit from a clinical and laboratory monitoring in this study. Moreover, these patients are taken to be vaccinated in the event of a pandemic influenza

Eligibility criteria: Inclusion criteria :

* informed consent signed
* Age between 18 to 64
* Patient suffering from chronic inflammatory bowel disease (Crohn's disease, ulcerative colitis, or indeterminate colitis)
* For patients receiving at least one immunosuppressive or anti-TNF therapy: treatment introduced for at least 3 months
* Patient willing to participate in the study throughout its duration and acceptance procedures related to the study (blood samples, self questionnaires, nasal swab and telephone follow-up)

Exclusion criteria :

* Patient treated by corticosteroid alone without immunosuppressive or anti-TNF
* For women, being pregnant or positive pregnancy test
* Known allergy to any component of the study vaccine or a history of hypersensitivity reaction to influenza vaccination
* Fever (at least 37.5°C measured orally) or acute infection in the week prior to vaccination
* Received influenza vaccination in the 6 months preceding enrollment
* Known history of progressive neuropathy or Guillain-Barre
* Known infection with HIV and/or HBV (Ag-HBs positive) and/or HCV
* Other causes of severe immune deficiency
* Cellular therapy, immunoglobulin infusions, of blood products or monoclonal antibodies (except anti-TNF) in the 3 months prior to vaccination
* Patient deprived of freedom by an administrative or court order
* Patient non affiliated to a health social security system

Primary outcomes:
measure: Seroconversion rate
timeFrame: 3-4 weeks after vaccination
Secondary outcomes:
measure: Seroconversion factor
timeFrame: 3 weeks and 6 months after vaccination
measure: Seroprotection rate against the three vaccine strains
timeFrame: 3 or 4 weeks after of vaccination
measure: Seroprotection rate in the general population
timeFrame: 3 weeks and 6 months after vaccination
measure: Seroconversion rate, geometric mean titers ratio before and after vaccination by haemagglutination inhibition assay
timeFrame: after 3 weeks of vaccination
measure: Comparison of seroprotection rates for each of the three vaccine strains obtained in each of three groups
timeFrame: 3 weeks and 6 months of vaccination
measure: Comparison of seroconversion factors obtained after 1 or 2 vaccinations in each of three groups of inflammatory bowel disease (IBD) and in the entire population
timeFrame: After 3 weeks of vaccination
measure: Number of influenza episodes and confirmed flu during each influenza peak season
timeFrame: 6 months after vaccination
measure: Occurrence of medical visits, emergency room visits, hospital admissions and deaths throughout the course of the study
timeFrame: 18 months after vaccination
measure: Occurrence and intensity of local and general adverse events within 5 days after vaccine administration
timeFrame: 5 days after vaccination
measure: Search of the determining factors to the influenza vaccine response
timeFrame: 18 months after vaccination
measure: Sub-immunological study
timeFrame: 6 months after vaccination
Other outcomes:
Locations:
city: Paris
country: France
facility: CIC Vaccinologie Hopital Cochin
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Odile LAUNAY, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Launay O, Abitbol V, Krivine A, Slama LB, Bourreille A, Dupas JL, Hebuterne X, Savoye G, Deplanque D, Bouhnik Y, Pelletier AL, Galtier F, Laharie D, Nachury M, Zerbib F, Allez M, Bommelaer G, Duclos B, Lucht F, Gougeon ML, Tartour E, Rozenberg F, Hanslik T, Beaugerie L, Carrat F; MICIVAX Study Group. Immunogenicity and Safety of Influenza Vaccine in Inflammatory Bowel Disease Patients Treated or not with Immunomodulators and/or Biologics: A Two-year Prospective Study. J Crohns Colitis. 2015 Dec;9(12):1096-107. doi: 10.1093/ecco-jcc/jjv152. Epub 2015 Sep 7.