Clinical trial NCT05304039: Phenotyping and Classifying Asthma Exacerbations
Official title: Phenotyping and Classifying of Childhood and Adult Asthma Exacerbations: Towards Personalised Treatment. An Observational Multicentre Study.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Asthma Attack
Keywords: Asthma
Exacerbation
Phenotyping
Classification
Treatment
Lead sponsor: Franciscus Gasthuis
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
name: TNO
First posted: 2022-03-31
Enrollment: 200
Sex: ALL
Minimum age (years): 12
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients aged 12 - 70 years, diagnosed with mild to severe asthma according to the Global Initiative for Asthma (GINA) guidelines. Patients will be included at the onset of a (severe) asthma exacerbation.

Brief summary: An observational study in patients between 12 and 70 years old with an acute asthma exacerbation, to determine the relation between phenotypical characteristics and the treatment response.

Detailed description: Rationale: Asthma is a heterogeneous inflammatory respiratory disease affecting 8 - 9% of the European population. Acute asthma exacerbation (AAE) is characterized as an acute worsening of symptoms and is treated inconsistently with steroids with or without antibiotics. In order to adjust and personalise exacerbation treatment, phenotyping and classifying of asthma exacerbations would be required. Therefore, we want to classify patients with AAEs phenotypically in relation to the treatment response.

Objective: The primary objective of the study is to determine the relationship between exacerbation treatment response at day 7 and the phenotypical characteristics of asthma exacerbations. Secondary objectives are 1) developing a prediction model based on biomarkers and/or clinical data to predict the treatment response of AAEs 2) comparing the environmental, inflammatory, microbiological and lipid parameters of patients diagnosed with asthma between exacerbation phase and recovery (baseline).

Study design: A prospective cohort multicentre study. Study population: Patients aged 12 - 70 years, diagnosed with mild to severe asthma according to the Global Initiative for Asthma (GINA) guidelines. Patients will be included at the onset of a severe asthma exacerbation.

Main study parameters/endpoints: Primary endpoint is the relation of phenotypical characteristics with treatment response at day 7, defined by 1) the physician - and patient rated global evaluation of treatment effectiveness (GETE) score 2) difference in Asthma Control Questionnaire 5 (ACQ-5) (\> 0.5) 3) difference in handheld spirometry values like forced expiratory volume (FEV1 ≥ 10%). Treatment response will be classified as excellent, good, moderate or poor. Secondary endpoints are 1) a prediction model for the treatment response of AAE 2) aetiology of the AAE 3) blood and local respiratory parameters; microbiota composition; lipid metabolomics and volatile compounds composition at baseline and AAE.

Eligibility criteria: Inclusion Criteria:

* Patient diagnosed with asthma according to the GINA guidelines between 12 and 70 years old. If patients are doctor's diagnosed with asthma based on clinical data, the further diagnostics will be performed to confirm the asthma diagnosis after the AAE.
* Mild to severe asthma, treated according to GINA guidelines with medium - or high dose inhaled corticosteroids (with or without LABA) or treated with a low dose inhaled corticosteroids combined LABA or leukotriene - receptor antagonist.
* Asthma exacerbation, indicated for systemic corticosteroids.
* Written personal and/or parental informed consent, prior to any study procedures.
* Eligibility and willingness to present during an asthma exacerbation at the Franciscus Gasthuis hospital.
* Ability to use e - health applications.

Exclusion Criteria:

* Immunosuppressive maintenance medication (azithromycin, systemic corticosteroids maintenance therapy and other) or recently (\< 6 weeks) discontinued these medications. (Desensitization therapy indicated for allergies can be included in the study)
* Maintenance medication or recently discontinued (\< 6 weeks) biologicals.
* Other underlying inflammatory or auto-immune diseases, such as rheumatologic disease.
* Involvement in the planning and/or conduct of the study (applies to both investigator staff and/or staff at the study site)
* Pregnancy, because of the possible altered immunological status.(31)
* Participation in an interventional study or randomised controlled trial.

Primary outcomes:
measure: Relation of phenotypical characteristics with treatment response
timeFrame: 7 days
Secondary outcomes:
measure: Prediction model for the treatment response of acute asthma exacerbation
timeFrame: 42 days
measure: Aetiology of the acute asthma exacerbation
timeFrame: 42 days
measure: Immune system and microbiome
timeFrame: 42 days
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis & Vlietland
Study officials:
affiliation: Franciscus Gasthuis & Vlietland
name: Gert-Jan Braunstahl, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Franciscus Gasthuis & Vlietland
name: Gerdien Tramper, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: