Efficacy Safety Study of Flu Vaccine in Immunodepression Patients

Phase 3

Completed

• Conditions: Inflammatory Bowel Disease (IBD)
• Interventions: Drug: Vaccine; Biological: Vaccine anti-H1N1

• Registration Number: NCT01022749
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2009-11-30
• Study First Submitted QC: 2009-11-30
• Study First Posted: 2009-12-01
• Primary Completion: 2011-07
• Status Verified: 2013-07
• Study Completion: 2013-07
• Last Update Submitted: 2013-08-02
• Last Update Posted: 2013-08-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 228

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
2	Vaccine	patients with IBD receiving immunosuppressants (TNF blockers excluded) (n=100)
3	Vaccine	patients with IBD receiving immunosuppressants including TNF blockers (n=100)
1	Vaccine	patients with IBD not receiving immunosuppressant (n=100)
4	Vaccine anti-H1N1	patients with IBD receiving immunosuppressants including TNF blockers (n=20)

Primary Outcome Measures

Name	Time	Method
Seroconversion rate	3-4 weeks after vaccination	Seroconversion rate in the overall population, defined as the geometric mean titers ratio post / pre-vaccination for each of the three vaccine strains

Secondary Outcome Measures

Name	Time	Method
Seroconversion factor	3 weeks and 6 months after vaccination	The seroconversion factor obtained for each of the three vaccine strains will be compared between each of the three groups (patients not receiving treatment, patients receiving immunosuppressants and patients receiving immunosuppressants including TNF) defined as the geometric mean titers ratio post / pre-vaccination for each of the three vaccine strains
Seroprotection rate against the three vaccine strains	3 or 4 weeks after of vaccination	The seroprotection rate (defined as the proportion of subjects attaining an anti-hemagglutinin titer ≥1:40) obtained 3-4 weeks after flu vaccination, against the three vaccine strains
Seroprotection rate in the general population	3 weeks and 6 months after vaccination	The seroprotection rate in the general population and according to the three groups of patients
Seroconversion rate, geometric mean titers ratio before and after vaccination by haemagglutination inhibition assay	after 3 weeks of vaccination	The seroconversion rate, geometric mean titers ratio before and after vaccination by haemagglutination inhibition (HI) assay before and after vaccination
Comparison of seroprotection rates for each of the three vaccine strains obtained in each of three groups	3 weeks and 6 months of vaccination	Comparison of seroprotection rates for each of the three vaccine strains obtained in each of three groups (patients not receiving treatment, patients receiving immunosuppressants and patients, receiving immunosuppressants including TNF)
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	After 3 weeks of vaccination
Number of influenza episodes and confirmed flu during each influenza peak season	6 months after vaccination
Occurrence of medical visits, emergency room visits, hospital admissions and deaths throughout the course of the study	18 months after vaccination
Occurrence and intensity of local and general adverse events within 5 days after vaccine administration	5 days after vaccination
Search of the determining factors to the influenza vaccine response	18 months after vaccination	Search of the determining factors to the influenza vaccine response: sex, age, previous vaccination against influenza, chronic smoking, the presence of other comorbidities (diabetes, renal failure, cirrhosis, ..), the nature of the IBD, the nature of the treatment of IBD and their duration, the number of immunosuppressive treatments associated and Disease Activity Index score of IBD at the vaccination time
Sub-immunological study	6 months after vaccination	Sub-immunological study each year of the study, the first and the second year (n=60, 20 patients per group): To determine if the LT-CD4 induction at J21-28 is correlated with the antibody anti-vaccines concentration measured within 6 months. To determine if the basal concentrations of anti-flu LT-CD4 at J21-J28 is correlated with the antibody anti-vaccines concentrations measured within 6 months.

Trial Locations

Locations (1)

CIC Vaccinologie Hopital Cochin; 🇫🇷 Paris, France