Clinical trial NCT05270278: Characteristics of Type 2- High Inflammatory Endotype of Asthma Using New Biomarkers From Peripheral Blood and Exhaled Air and Its Effect on the Outcome of Therapy
Official title: Characteristics of Type 2- High Inflammatory Endotype of Asthma Using New Biomarkers From Peripheral Blood and Exhaled Air and Its Effect on the Outcome of Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma; Eosinophilic
Asthma Chronic
Bronchial Asthma
Asthma, Bronchial
Keywords: airway inflammation
airway obstruction
airway disease
serious asthma
pulmonary
biological therapy
omalizumab
dupilumab
mepolizumab
benralizumab
biomarkers
Exhaled Nitric Oxide Levels (FeNO)
alveolar NO
cross-sectional study
exploratory analysis
conservative treatment
Lead sponsor: Value Outcomes Ltd.
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2022-03-08
Enrollment: 89
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The patients with severe AB type 2 - high (eosinophilic) and type 2- low (non-eosinophilic)

Brief summary: The goal of this study is to identify reliable, valid, easily measurable, interpretable, and useful biomarkers in peripheral blood and exhaled air by people with severe asthma for a more accurate description of the pathogenetic processes of asthma-related to the inflammatory endotype and the choice of biologic therapy.

Detailed description: According to WHO, asthma bronchiale (AB) is the most frequent non-infectious disease in adults. There are 340 million patients with AB in the world. Approximately 500 000 patients in the Czech Republic are suffering from AB and 2,1 % have severe AB with the indication for conventional anti-inflammatory treatment. This subgroup of patients represents significantly high costs for the healthcare system.

There are many clinical phenotypes and molecular endotypes of AB and each of these groups has a different response to treatment. In the Czech republic is recommended classification into two main groups: eosinophil AB (type 2- high) and non-eosinophil AB (type 2- low). Eosinophil AB is furthered classified into two groups: eosinophil allergic (Th2-high) and eosinophil non-allergic (ILC2-high).

New biologicals, indicated for patients with the most severe form of AB, have entered the market during the last 15 years. These biologicals have confirmed their potential in randomized controlled studies. It can be assumed that there are 4 000 - 5000 patients suffering from this type of AB who could be indicated to this treatment in the Czech republic but, unfortunately, only 10 % of them have the access to such therapies in real practice.

Recommended markers of type 2- high AB don´t have strictly set critical values that are often unspecific, unstable in time, and often affected by other diseases or treatments. Some of the widely accepted predictors of response to biological treatment are eosinophilia, allergic reactivity, level of total and allergic-specific IgE, NO production in inhaled air (FeNO), gender, number of previous exacerbations, and duration of disease. Some of these predictors are used as decision criteria also in Global Initiative for Asthma (GINA) guidelines.

With respect to these facts, enormous efforts are being made worldwide to search for new biomarkers, which would be reliable, valid, easily measurable, interpretable, and useful for a more accurate description of the pathogenetic processes of asthma

Eligibility criteria: \> Group 1 \<

Inclusion Criteria:

* severe persistent eosinophilic AB (type 2- high)
* initiated biological treatment against IL-5 or IL-5R (mepolizumab, benralizumab) on this study visit
* judged by the treating physician, the patient cannot be indicated to treatment against anti IgE or anti IL-4R (omalizumab, dupilumab)
* signed informed consent
* signed consent to the processing of personal data
* willingness and ability to undergo examination

Exclusion Criteria:

* active smoker
* BMI higher than 40kg/m2
* ongoing oncological disease or oncological disease during the last 12 months
* severe cardiovascular disease
* uncontrolled diabetes mellitus
* contraindication of choosen biological treatment per SPC

  * Group 2 \<

Inclusion Criteria:

* severe persistent eosinophil AB (type 2- high)
* initiated biological treatment against IgE or IL-4R (omalizumab, dupilumab) at this study visit
* judged by the treating physician, a patient cannot be indicated to treatment against anti IL-5 or anti IL-5R (mepolizumab, benralizumab)
* signed informed consent
* signed consent to the processing of personal data
* willingness and ability to undergo examination

Exclusion Criteria:

* active smoker
* BMI higher than 40kg/m2
* ongoing oncological disease or oncological disease during the last 12 months
* severe cardiovascular disease
* uncontrolled diabetes mellitus
* contraindication of choosen biological treatment per SPC

  * Group 3 \<

Inclusion Criteria:

* severe persistent eosinophil AB (type 2- high)
* initiated biological treatment against IgE or IL-4R (omalizumab, dupilumab) or against IL-5 or IL-5R (mepolizumab, benralizumab) at this study visit was
* judged by the treating physician, the patient could be potentially indicated to treatment with all 4 alternatives
* signed informed consent
* signed consent to the processing of personal data
* willingness and ability to undergo examination

Exclusion Criteria:

* active smoker
* BMI higher than 40kg/m2
* ongoing oncological disease or oncological disease during the last 12 months
* severe cardiovascular disease
* uncontrolled diabetes mellitus
* contraindication of choosen biological treatment per SPC

  * Group 4 \<

Inclusion Criteria:

* severe persistent non-eosinophil AB (type 2- low)
* judged by the treating physician, the patient cannot be indicated for biological treatment
* signed informed consent
* signed consent to the processing of personal data
* willingness and ability to undergo examination

Exclusion Criteria:

* active smoker
* BMI higher than 40kg/m2
* ongoing oncological disease or oncological disease during the last 12 months
* severe cardiovascular disease
* uncontrolled diabetes mellitus

Primary outcomes:
measure: Laboratory parameters (peripheral blood) - blood count
timeFrame: Baseline
measure: Laboratory parameters (peripheral blood) - atopy
timeFrame: Baseline
measure: Laboratory parameters (peripheral blood) - rheumatology
timeFrame: Baseline
measure: Laboratory parameters (peripheral blood) - immunology
timeFrame: Baseline
measure: Laboratory parameters (peripheral blood) - flow cytometry (FACS)
timeFrame: Baseline
measure: Clinical parameters (exhaled air) - FeNO
timeFrame: Baseline
measure: Clinical parameters (exhaled air) - alveolar NO
timeFrame: Baseline
measure: Clinical parameters (exhaled air) - eNOSE
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Hradec Králové
country: Czechia
facility: Fakultní nemocnice Hradec Králové
state: Královehradecký Kraj
Study officials:
affiliation: Fakultní nemocnice Hradec Králové
name: Jakub Novosad, MUDr.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: