Clinical trial NCT03925415: BRazilian Asthmatics Patients EOSinophilic Profile (BRAEOS)
Official title: A National, Observational, Cross-Sectional, Multicenter Study to Estimate the Prevalence of an Eosinophilic Phenotype Among Severe Asthma Patients in Brazil
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Severe Asthma
Keywords: Severe Asthma
Eosinophilic Asthma
Eosinophilic Phenotype
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Medical Writer: Dr. Rodrigo Athanazio
name: CRO: CTI-Eurotrials
First posted: 2019-04-24
Enrollment: 414
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will include adult patients with severe asthma, as per the definition of the International ERS/ATS Guidelines on Definition, Evaluation and Treatment of Severe Asthma, and who attend their routine clinical appointment at Brazilian centres specialized in the management of severe asthma.

Brief summary: Asthma is a complex and heterogeneous disease. Severe asthma is recognised as a major unmet need that poses a great burden on the healthcare system. While accounting for only a small proportion of the total asthmatic population, asthma-related costs are 1.7 to 4-fold higher than those observed in the mild-persistent asthma population and the associated personal and societal impact is significant.

Severe asthma is not considered to be a single disease, but can be divided into several phenotypes, owing to the variety of inflammatory, clinical and functional characteristics that it can present with. One of the proposed and most studied phenotypes is severe eosinophilic asthma. Patients with severe asthma that is accompanied with a high concentration of eosinophils require greater healthcare resource use, overall greater disease management costs and have a much more impaired QoL than those who do not present with raised eosinophilia.

While the number of targeted treatments for asthma management has been growing in recent years, the heterogeneity of clinical presentations, treatment responses and inflammatory processes involved represents an added challenge for health care professionals. Thus, severe asthma management is a complex endeavour and a thorough and up to date understanding of the pathophysiologic characteristics of the patient population promotes effective therapeutic decision-making.

The purpose of this observational, cross-sectional, multicentre study is to determine the prevalence of an eosinophilic phenotype of blood eosinophil count \> 300 cells/mm3 among severe asthma patients followed at Brazilian sites specialized in the management of severe asthma. The prevalence of an atopic phenotype, asthma control, QoL and burden of disease will also be studied.

Detailed description: Knowledge of the prevalence of eosinophilia among adult, severe asthma patients in Brazil is limited. Moreover, data on the prevalence of an atopic phenotype within the adult, severe asthma population is scarce. Severe asthma management is a complex endeavour and a thorough and up to date understanding of the pathophysiologic characteristics of the patient population facilitates therapeutic decisions that effectively lead to disease control.

The purpose of this observational, cross-sectional, multicentre study is to determine the prevalence of an eosinophilic phenotype of blood eosinophil count \> 300 cells/mm3 among severe asthma patients followed at Brazilian sites specialized in the management of severe asthma. The prevalence of an atopic phenotype, asthma control, QoL and burden of disease will also be studied. It is expected that this study will contribute to the understanding of severe asthma in Brazil, ultimately helping to inform therapeutic decisions and addressing patients' needs.

Eligibility criteria: Inclusion Criteria:

* Male or female subject, aged 18 years or older at the time of study entry.
* Subject followed at a participating centre and attending a routine clinical appointment.
* Subjects with evidence of asthma of either:

  * Documented airway reversibility (forced expiratory volume in one second (FEV1) ≥12% and 200 mL) using the maximum post-bronchodilator procedure OR
  * Documented airway hyperresponsiveness (provocative concentration of methacholine causing a ≥20% fall in FEV1) OR
  * Documented airflow variability in FEV1 ≥20% between two consecutive lung function assessments prior to study entry (FEV1 values recorded during exacerbations should not be considered for this criterion)
* Subjects with a diagnosis of severe asthma for at least one year, according to the criteria of the International ERS/ATS Guidelines on Definition, Evaluation and Treatment of Severe Asthma (6), i.e.:

  * Asthma which requires treatment with guidelines suggested medications for GINA steps 4-5 asthma (high dose ICS (Appendix A) and LABA or leukotriene modifier/theophylline) for the previous year; or
  * Systemic CS for ≥50% of the previous year to prevent it from becoming "uncontrolled" or which remains "uncontrolled" despite this therapy.
* Subject with accurate and complete medical records at the centre.
* Subject that voluntarily signed and dated the informed consent form prior to study entry.

Exclusion Criteria:

* Subjects experiencing a moderate or severe asthma exacerbation as per the Official ATS/ERS Statement on Asthma Control (22) at the time of the study entry, or who had a moderate or severe asthma exacerbation less than 4 weeks prior to study entry.
* Subjects whose pharmacological therapy for asthma was modified in the 3 months prior to study entry.
* Subjects diagnosed with at least one of the following:

  * Lung cancer
  * Pulmonary fibrosis
  * Allergic bronchopulmonary aspergillosis
  * Eosinophilic granulomatosis with polyangiitis
  * Clinically relevant bronchiectasis or bronchiectasis associated with cystic fibrosis and/or allergic bronchopulmonary aspergillosis.
  * Chronic obstructive pulmonary disease associated with a smoking history ≥10 pack-years and/or history of exposure to biomass fuel combustion
* Subjects who are currently smokers or who have a history of smoking ≥ 10 pack-years.

Primary outcomes:
measure: Prevalence of an eosinophilic phenotype of blood eosinophil count > 300 cells/mm3 among severe asthma patients in Brazil.
timeFrame: 8-month
Secondary outcomes:
measure: Prevalence of an eosinophilic phenotype of blood eosinophil count > 150 cells/mm3.
timeFrame: 8-month
measure: Prevalence of an atopic phenotype, defined by a pre-existing history of atopy and total serum IgE > 100 UI/mL.
timeFrame: 8-month
measure: Prevalence of atopy, as defined by a pre-existing history of atopy and total serum IgE > 100 UI/mL, among patients that present an eosinophilic phenotype of blood eosinophil count > 300 cells/mm3.
timeFrame: 8-month
measure: Annual exacerbation rate.
timeFrame: 12-month
measure: Patient-reported QoL using the St. George's Respiratory Questionnaire (SGRQ) results.
timeFrame: 8-month
measure: Asthma control using the Asthma Control Questionnaire 7 (ACQ 7) results.
timeFrame: 8-month
measure: Burden of disease using the GAD 7 scale.
timeFrame: 8-month
measure: Burden of disease using the PHQ-9.
timeFrame: 8-month
measure: Burden of disease using the WPAI: Asthma questionnaire results.
timeFrame: 8-month
measure: Chronic oral corticosteroid (OCS) rate.
timeFrame: 8-month
Other outcomes:
Locations:
city: Blumenau
country: Brazil
facility: Research Site
city: Goiania
country: Brazil
facility: Research Site
city: Londrina
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sorocaba
country: Brazil
facility: Research Site
Study officials:
affiliation: Associação PROAR - Associação do Programa de Controle da Asma e da Rinite Alérgica na Bahia
name: Adelmir Machado, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Santa Casa de Misericórdia de Vitória
name: Faradiba Serpa, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CLARE - CLINICA DE PNEUMOLOGIA S/S
name: Marcelo Rabahi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital São Lucas da PUCRS
name: Daniela Blanco, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital DIA do Pulmão / Complexo de Prevenção, Diagnóstico, Terapia e Reabilitação Respiratória LTDA
name: Marina Lima, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: InCor - Instituto do Coração - HCFMUSP.
name: Rafael Stelmach, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HCUSP - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
name: Pedro Francisco Giovina-Bianchi Júnior, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidade Estadual de Londrina
name: Alcindo Cerci Neto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clínica de Alergia Martti Antila / CMPC Pesquisa Clínica
name: Martti Antila, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HCUSP RP - Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
name: Luisa Karla Arruda, MD
role: PRINCIPAL_INVESTIGATOR
References: