Clinical trial NCT04509921: Adjustment of Asthma Treatment in Children Based on an Indirect Hyperresponsiveness Test
Official title: Adjustment of Asthma Treatment in Children Based on an Indirect Hyperresponsiveness Test - a Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma in Children
Keywords: asthma
bronchoprovocation
inhaled corticosteroids
Lead sponsor: National Institute for Tuberculosis and Lung Diseases, Poland
Sponsor class: OTHER
Collaborators: name: The Regional Public Hospital in Lesko, Poland
name: University of Rzeszow
First posted: 2020-08-12
Enrollment: 108
Sex: ALL
Minimum age (years): 7
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of the study is to assess the usefulness of the indirect bronchial hyperresponsiveness test (with hypertonic NaCl) in determining the optimal dose of inhaled steroids to maintain asthma control.

The study was designed as a prospective, real-life, randomized, interventional study. This single-site study is performed at the Allergology Clinic in Lesko.

The study included participants aged 7-15 years who met the eligibility criteria. Eligible participants were selected from a pool of 231 patients with mild asthma, under the care of the Allergology Clinic of the Regional Public Hospital in Lesko (Poland). All participants were diagnosed with chronic mild asthma for at least two years.

Subjects initially enrolled in the study had good asthma control maintained for at least 3 months on low / medium-dose ICS monotherapy, with no exacerbations requiring systemic corticosteroids in the previous 3 months, no respiratory tract infection in last month, and an FEV1 above 80% expected.

Finally, 108 children were enrolled in the study. They were aged 7-15 years, with active mild asthma, confirmed by the presence of bronchial hyperreactivity and symptoms of asthma, emerging after discontinuation of anti-inflammatory treatment.

Participation in the study lasted one year.

The study includes:

4-week run-in period (withdrawal phase) after discontinuation of anti-inflammatory treatment (ICS) with clinical symptoms and medication use recording, completed by the patient and parents.

At the end of this period, spirometry was performed, bronchial hyperreactivity was assessed with the hyperosmolar salt provocation, and the parameters of inflammation were measured: orally exhaled nitric oxide concentration (NO) and peripheral blood eosinophilia. The anti-inflammatory treatment was then resumed (with ICS in the previous doses).

Only patients with active asthma and increased bronchial responsiveness (DRS\>0.55) were qualified for the main study. Stratified randomization was performed for age, clinical symptoms, and the degree of bronchial hyperresponsiveness. On this basis, the division into 2 research groups was made:

* a symptom-only monitored treatment group
* a group in which therapy changes were based on the symptoms and degree of bronchial hyperresponsiveness (BHR group).

Patients/parents were provided by an established algorithm for managing asthma symptoms/exacerbations. In the case of loss of asthma control, a beta-agonist was administered (temporarily) and the dose of ICS quadrupled. Patients had the possibility of additional visits - if necessary. Especially, severe exacerbations were verified by the attending physician, and on this basis, oral steroids would be considered.

Throughout the study, the participants kept daily observation charts (clinical symptoms and drug use) and peak expiratory flow rate (PEFR) measurements.

The telephone report was made monthly with the number of days with asthma symptoms and medications used, and this was recorded in the documentation of the study.

The clinical evaluation was performed every 3 months with symptom evaluation, spirometry, exhaled NO, peripheral blood eosinophilia, and BHR measurements (half of the patients).

The treatment adjustments were guided by the patient's and parent's reporting of symptoms, and additionally by the results of periodic clinical assessment (including the assessment of bronchial hyperresponsiveness in the BHR group). This means that the level of treatment intensity (ICS dose) was based on symptom monitoring only in the observation group, and additionally took into account the level of bronchial responsiveness in the BHR monitoring group.

The study was completed after one year of follow-up (4 visits every 3 months). The primary endpoint of the study: the number of asthma exacerbations in both study arms.

Secondary endpoints:

* days with symptoms
* asthma medication days
* final dose of ICS
* spirometry (FEV1, MMEF)
* bronchial hyperreactivity (BHR group only)
* nitric oxide in the exhaled air
* peripheral blood eosinophilia.


Eligibility criteria: Inclusion Criteria:

* mild asthma with a stable course of at least 3 months
* good adherence to treatment with low dose ICS

Exclusion Criteria:

* infection or exacerbation of asthma requiring the use of systemic steroids (or changes in the dose of inhaled steroids) in the last 3 months before the study
* other chronic lung diseases or general diseases affecting the respiratory system
* tobacco smoking
* FEV1 below 80% of the predicted value

Primary outcomes:
measure: asthma exacerbations
timeFrame: 12 months
Secondary outcomes:
measure: the percentage of participants with asthma exacerbations
timeFrame: 12 months
measure: time to the first asthma exacerbation
timeFrame: 12 months
measure: ICS dose
timeFrame: 12 months
measure: days with symptoms
timeFrame: 12 months
measure: days with asthma medication
timeFrame: 12 months
measure: blood eosinophilia
timeFrame: 12 months
measure: exhaled nitric oxide
timeFrame: 12 months
measure: spirometry
timeFrame: 12 months
Other outcomes:
Locations:
city: Lesko
country: Poland
facility: The Regional Public Hospital in Lesko, Poland
Study officials:
References:
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