Clinical trial NCT02904590: A Prospective Study on the Incidence and Risk Factors Related to Infection in Patients With Inflammatory Bowel Disease
Official title: A Prospective Study on the Incidence and Risk Factors Related to Infection in Patients With Inflammatory Bowel Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Inflammatory Bowel Diseases
Keywords: IBD
Infection
Lead sponsor: Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
Sponsor class: OTHER
First posted: 2016-09-19
Enrollment: 1204
Sex: ALL
Minimum age (years): 1
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Incident cases of IBD registered on ENEIDA data base

Brief summary: The purpose of this study is to determine the incidence and risk factors related to Infection in patients with Inflammatory Bowel Disease (IBD)

Detailed description: IBD could lead to an increased risk of infections, particularly related to immunosuppressive therapy. The true effect of having IBD in the development of infections has not been studied in depth since the cohort studies are scarce and the results of studies with different approaches are contradictory.

The limited time period of former studies may not be enough to assess infectious complications that may occur in a long term period.

Moreover, certain polymorphisms demonstrated to confer a higher risk of opportunistic infections under immunosuppressive conditions, for instance HIV, patients with cystic fibrosis and Candida' infections. For this reason, it seems reasonable to think that genetic factors might play a role in the risk of opportunistic infections in IBD.

The hypothesis of this study is that patients with IBD have an increased risk of infection by immunosuppressive treatment.

TYPE OF STUDY Prospective cohort study that evaluates the effect of immunosuppression and other clinical factors in the onset of infection in IBD

STUDY DESIGN PATIENTS \& METHODS This study is aimed to all incidental patients diagnosed with Crohn's disease and ulcerative colitis included in the ENEIDA database.

METHODS An infection would be considered as relevant when: 1) requires hospital admission, 2) leads to death or endangers the patient's life (ICU admission, presence of hemodynamic instability, sepsis, tracheal intubation, vasoactive drug requirement), 3) must be treated with specific antibiotics (antibacterials, antivirals, antifungals) 4) affects recurrently (herpes virus, papilloma virus, etc). 5) requires change/withdrawal of immunosuppressive or biological treatment.

The appearance of relevant infection will be prospectively evaluated, performing a subanalysis at 3 and 5 years using ENEIDA platform. ENEIDA is a database from a Spanish national study in IBD on genetic and environmental determinants run under GETECCU (Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa) supervision. This database basically comprises: demographic characteristics, type of IBD, immunosuppressant treatment, biological treatment or surgery)

At the time of inclusion the following variables should be available (and are mandatory): demographic characteristics, type of IBD, date of diagnosis, phenotypic characteristics of the disease, history of serious infections, information on received treatments particularly the exposure to immunosuppressants, biological treatment or surgery and whether an infection has occurred as a complication of the three treatment groups. It should also be collected the following serologic details: hepatitis type B virus C, HIV, tuberculosis (TB), varicella zoster status.

At the time of registration a blood sample (10cc) will be drawn and sent to a biobank to analyze the DNA for genetic research.

STUDY ANALYSIS Sample calculation

The main objective of this study is to determine the percentage of infections in IBD and the related risk factors for the development of infections in patients with IBD. Given that the reported prevalence of infection varies between 6 and 10%the formula for estimating endless samples, establishing:

* Security level of the confidence interval at 95%
* Expected value for the worst case scenario of 6% (prevalence of infection)
* Precision of 1.5%
* The minimum sample number is set to 963, and assuming a loss rate of 20%

With these assumptions, the total number of patients to be included is 1204 patients.

The statistical analysis will be in three steps: (1) independent clinical factors analysis, (2) genetic factors infection-related analysis and (3) clinical and genetic factors infection- related analysis.

Baseline and follow up data will be compared among patients who develop infection and those who do not. Quantitative variables will be contrast by T-student and Mann-Whitney test. Qualitative variable will be contrast by X2 or Fisher test. Logistic regression will be conducted to analyze independent associations between variables and Kaplan-Meier test to calculate survival curves.

An analysis of Cox proportional hazards will be conducted to assess the effect of exposure to independent predictors of the risk of significant infection or mortality.

Finally the intensity of the significant associations will be measured by calculating the OR, HR and confidence interval of 95%.

Eligibility criteria: Inclusion criteria:

* All incidental patients with IBD controlled at each participating center, registered in the ENEIDA database could be included, until the expected study sample is reached (n=1204 patients).
* An incidental IBD case is any patient with a diagnosis of Crohn's disease, ulcerative colitis and unclassified colitis after 3-6 month of the conclusive diagnosis of IBD.

Exclusion Criteria:

* HIV infection or any congenital immunodeficiency at the time of inclusion.
* To be under any immunosuppressant therapy for another reason other than IBD at IBD diagnosis.
* No consent to participate.

Primary outcomes:
measure: The incidence of infection and type of infection in patients with ulcerative colitis and Crohn's disease, regardless of treatment received. ulcerative colitis and Crohn's disease, regardless of treatment received.
timeFrame: Change from baseline incidence and type of infection at 3 and 5 years
measure: Clinical, demographic, epidemiologic and genetic factors associated with the risk of infection in patients with IBDassociated with the risk of infection in patients with IBD.
timeFrame: Change from baseline and at 3 and 5 years
Secondary outcomes:
measure: The effect of duration and immunosuppressive potency in the development of infections
timeFrame: at baseline and at 3 and 5 years
measure: The impact of infection on morbidity and mortality in patients with IBD.
timeFrame: at baseline and at 3 and 5 years
measure: The type of infections in IBD patients grouped by systems and whether they are opportunistic or not.
timeFrame: at baseline and at 3 and 5 years
Other outcomes:
Locations:
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
state: Asturias
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Granollers
country: Spain
facility: Hospital General de Granollers
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Manresa
country: Spain
facility: Althaia, xarxa assistencial universitaria de Manresa
state: Barcelona
city: Sabadell
country: Spain
facility: Corporació Sanitària Parc Taulí
state: Barcelona
city: Sant Joan Despí
country: Spain
facility: Hospital Moisès Broggi
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
state: Barcelona
city: Galdakao
country: Spain
facility: Hospital de Galdakao
state: Bilbao
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Tomelloso
country: Spain
facility: Hospital General de Tomelloso
state: Ciudad REAL
city: Fuenlabrada
country: Spain
facility: Hospital Universitario Fuenlabrada
state: Madrid
city: San Sebastián De Los Reyes
country: Spain
facility: Hospital Infanta Sofía
state: Madrid
city: Vigo
country: Spain
facility: Complexo Hospital Universitario de Vigo
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Córdoba
country: Spain
facility: Hospital Reina Sofía
city: Girona
country: Spain
facility: Hospital Universitari Dr. Josep Trueta
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital De La Princesa
city: Terrassa
country: Spain
facility: Consorci hospitalari de Terrassa
city: Valencia
country: Spain
facility: Hospital Universitari La Fe
city: València
country: Spain
facility: Hospital Clínic de València
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
Study officials:
affiliation: Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
name: Yamile Zabana
role: PRINCIPAL_INVESTIGATOR
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citation: Obrador A, Lopez San Roman A, Munoz P, Fortun J, Gassull MA; Grupo Espanol de Trabajo de Enfermedad de Crohn y Colitis Ulcerosa (GETECCU). [Consensus guideline on tuberculosis and treatment of inflammatory bowel disease with infliximab. Spanish Working Group on Crohn Disease and Ulcerative Colitis]. Gastroenterol Hepatol. 2003 Jan;26(1):29-33. doi: 10.1016/s0210-5705(03)70338-0. No abstract available. Spanish.
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