N/A
N=130
Impulse Oscillometry Measurements in Severe Eosinophilic Asthmatics Before and After Anti-IL-5 Factor Initiation
Severe Asthma
Bottom Line
View on ClinicalTrials.gov: NCT05147155 ↗Enrolled (actual)
130
Serious AEs
0.0%
Results posted
Feb 2025
Primary outcome: Primary: Airway Resistance at 5 Hz (R5) at Baseline (Pre-mepolizumab Initiation) — 0.51; 0.39; 0.43 kPa/L/s
Study Design & Population
- Study type
- Observational
- Phase
- N/A
- Interventions
- Mepolizumab (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Thessaly
- Primary completion
- Oct 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Airway Resistance at 5 Hz (R5) at Baseline (Pre-mepolizumab Initiation) |
0.51; 0.39; 0.43 | — |
| PRIMARY Airway Resistance at 20 Hz (R20) at Baseline |
0.4; 0.3; 0.3 | — |
| PRIMARY Difference Between Airway Resistance at 5 Hz (R5) and 20 Hz (R20) at Baseline / (R5-R20) at Baseline |
0.12; 0.05; 0.09 | — |
| PRIMARY Reactance Area (AX) at Baseline |
1.2; 0.5; 0.7 | — |
| PRIMARY Resonant Frequency (Fres) at Baseline |
35; 9; 16 | — |
| PRIMARY Respiratory Reactance at 5 Hz (X5) at Baseline |
-0.1; -0.08; -0.09 | — |
| PRIMARY Airway Resistance at 5 Hz (R5) at Week 4. |
0.49; 0.3; 0.43 | — |
| PRIMARY Airway Resistance at 20 Hz (R20) at Week 4. |
0.4; 0.3; 0.3 | — |
| PRIMARY Difference Between Airway Resistance at 5 Hz (R5) and 20 Hz (R20) at Week 4/ R5-R20 at Week 4. |
0.10; 0.04; 0.09 | — |
| PRIMARY Reactance Area (AX) at Week 4 |
0.7; 0.5; 0.7 | — |
| PRIMARY Resonant Frequency (Fres) at Week 4. |
17; 10; 16 | — |
| PRIMARY Respiratory Reactance at 5 Hz (X5) at Week 4. |
-0.1; -0.08; -0.09 | — |
| PRIMARY Airway Resistance at 5 Hz (R5) at Week 12 |
0.51; 0.3; 0.43 | — |
| PRIMARY Airway Resistance at 20 Hz (R20) at Week 12 |
0.4; 0.3; 0.3 | — |
| PRIMARY Difference Between Airway Resistance at 5 Hz (R5) and 20 Hz (R20) at Week 12 / R5-R20 at Week 12 |
0.13; 0.04; 0.09 | — |
| PRIMARY Reactance Area (AX) at Week 12 |
0.7; 0.5; 0.7 | — |
| PRIMARY Resonant Frequency (Fres) at Week 12 |
17; 10; 16 | — |
| PRIMARY Respiratory Reactance at 5 Hz (X5) at Week 12 |
-0.1; -0.08; -0.09 | — |
| PRIMARY Airway Resistance at 5 Hz (R5) at Week 26. |
0.41; 0.3; 0.43 | — |
| PRIMARY Airway Resistance at 20 Hz (R20) at Week 26. |
0.4; 0.3; 0.3 | — |
| PRIMARY Difference Between Airway Resistance at 5 Hz (R5) and 20 Hz (R20) at Week 26 / R5-R20 at Week 26. |
0.03; 0.04; 0.09 | — |
| PRIMARY Reactance Area (AX) at Week 26. |
0.6; 0.5; 0.7 | — |
| PRIMARY Resonant Frequency (Fres) at Week 26. |
17; 10; 16 | — |
| PRIMARY Respiratory Reactance at 5 Hz (X5) at Week 26. |
-0.08; -0.08; -0.09 | — |
Summary
Eosinophilic inflammation in the small airways of patients with severe asthma is considered to be an important marker of disease severity. In clinical trials, treatment with mepolizumab reduces exacerbation rates by almost a half along with modest improvements in symptom scores and forced expiratory volume in 1 s (FEV1) early after the first month of commencing mepolizumab treatment. However, there is an apparent discrepancy between major patient-reported outcomes and lung function that should be explored.
It has recently been reported that mepolizumab improves small airway function in severe eosinophilic asthma as detected by multiple-breath nitrogen washout test. The improvement in small airway function was seen rapidly after the first mepolizumab injection and was associated with a sustained response in the majority of patients. However, gaps in knowledge about the choice of device, gas, and standardization across systems are key issues leading the committee to conclude that multiple-breath nitrogen washout test is not ready for use as a clinical trial endpoint in asthmatics.
The investigators hypothesize that early improvement in small airway function may be a significant contributor to the therapeutic response of anti-IL-5 monoclonal antibody therapy in patients with severe uncontrolled eosinophilic asthma. The investigators speculate that SAD could be effectively evaluated using IOS. Consequently, this study could lead to novel SAD subtypes with possible clinical relevance in the context of treatment with anti-IL-5 factor. The investigators hypothesize that healthy individuals and patients with severe controlled asthma would disclose a lesser extent of SAD than patients with severe uncontrolled eosinophilic asthma with or without fixed airway obstruction.
Eligibility Criteria
Inclusion Criteria
- Written informed consent
- Male or female outpatient aged 18 to 82 years inclusive
- History of bronchial asthma for at least six months as defined by ATS criteria.
- The patients will be required to have one or more of the following objective physiological criteria: positive results on methacholine or mannitol challenge during the previous year, bronchodilator reversibility to 400 mg of inhaled Salbutamol of FEV1 ≥12% and 200ml or peak flow variability of ≥20% over two weeks.
- Diagnosis of severe asthma, defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming uncontrolled or that remains uncontrolled despite this therapy.
- All patients will be medicated with at least 880 μg of fluticasone propionate or the equivalent by inhalation per day and at least three months of treatment with an additional controller. Patients will be allowed to continue their anti-asthma therapy throughout the study.
- Patients should have uncontrolled asthma commencing mepolizumab treatment, based on investigator assessment, including one or both of the following:
- Poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma), defined as ACQ consistently ⩾1.5 or ACT<20.
- Frequent exacerbations (≥2/year) requiring oral corticosteroids, or severe exacerbations (≥1/year) requiring hospitalization or burst of systemic corticosteroids (≥3 days).
- All patients will have an eosinophil count of at least 150 cells per microliter in the peripheral blood at screening or at least 300 cells per microliter at some time during the previous year.
Exclusion Criteria
Principal exclusion criteria:
- Diseases and health status: clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation suffering from COPD (i.e., chronic bronchitis or emphysema) and/or other relevant lung diseases causing alternating impairment in lung function
- Asthmatic patients and healthy controls currently smoking or with a smoking pack history greater than 10 will be excluded.
Common exclusion criteria:
- pregnancy
- intention to become pregnant during the course of the study
- breastfeeding
- participation in another study within the 30 days preceding and during the present study
- known or suspected non-compliance, alcohol or drug abuse
- inability to follow the procedures of the study, e.g., due to language problems, psychological disorders
Data sourced from ClinicalTrials.gov (NCT05147155). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.