Small Airway DysfunctionPhase 4NCT07809555
Extrafine ICS/LABA Versus As-Needed SABA for Small Airway Dysfunction in Symptomatic Patients With Preserved Spirometry
A Phase 4 study testing Beclomethasone dipropionate/formoterol fumarate (extrafine) and Salbutamol in people with Small Airway Dysfunction, run by Yi-Han Hsiao at 1 site in Taiwan.
Trial summary
This study evaluates whether 4 weeks of extrafine inhaled corticosteroid/long-acting β2-agonist (beclomethasone dipropionate/formoterol fumarate, BDP/FOR) therapy improves clinical, physiological, and type 2 inflammatory outcomes compared with as-needed short-acting β2-agonist (SABA, salbutamol) alone in symptomatic… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Small Airway Dysfunction
- What is being tested?
- Beclomethasone dipropionate/formoterol fumarate (extrafine) and Salbutamol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 93 participants
- Where
- 1 siteTaiwan
- Study dates
- 12 Aug 2021to 29 Nov 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥20 years
- Chronic respiratory symptoms (cough, sputum, chest tightness, dyspnea, or wheezing) for ≥8 weeks
- Preserved spirometry: FEV1/FVC ≥0.7, FVC ≥80% predicted, and negative bronchodilator reversibility (increase in FEV1 or FVC <12% and <200 mL after salbutamol)
- IOS-defined small airway dysfunction and small airway reversibility (SAR): AX >0.44 kPa/L with post-bronchodilator reduction in AX ≥35% after salbutamol inhalation
Who cannot join
- Age <20 years
- Impaired spirometry (FEV1/FVC <0.7, FVC ≤80% predicted, or positive bronchodilator reversibility)
- Absence of SAD or lack of significant SAR
- Respiratory symptoms absent or <8 weeks
- Acute respiratory condition within 4 weeks before enrollment (upper/lower respiratory tract infection, acute exacerbation, pneumonia requiring antibiotics, ED visit or hospitalization)
- Current diagnosis of COPD, chronic respiratory infection, or structural lung disease (active/prior tuberculosis, bronchiectasis, interstitial/restrictive lung disease, arteriovenous malformation, or prior pulmonary surgery)
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- Use of any bronchodilator (oral/inhaled), theophylline, steroid (inhaled/oral/IV), or beta-blocker within 4 weeks before enrollment
- Known hypersensitivity to beclomethasone dipropionate/formoterol fumarate or salbutamol
- Contraindication to pulmonary function testing or venous blood sampling (severe/unstable cardiovascular disease, recent major thoracic/abdominal surgery, unresolved pneumothorax, uncontrolled bronchospasm or hemoptysis, need for FiO2 >50%, impaired consciousness or dementia)
- Other physician-assessed unsuitability for pulmonary function testing or blood sampling
- Incomplete informed consent
- Known HIV/AIDS infection
- Pregnant or breastfeeding women
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
Taipei Veterans General Hospital, Department of Chest Medicine
Taipei, 11217
About this study
Official title: Effects of Extrafine Inhaled Corticosteroid/Long-Acting β2-Agonist Therapy on Small Airway Dysfunction and Type 2 Inflammatory Biomarkers in Symptomatic Patients With Preserved Spirometry
This study evaluates whether 4 weeks of extrafine inhaled corticosteroid/long-acting β2-agonist (beclomethasone dipropionate/formoterol fumarate, BDP/FOR) therapy improves clinical, physiological, and type 2 inflammatory outcomes compared with as-needed short-acting β2-agonist (SABA, salbutamol) alone in symptomatic patients who have preserved conventional spirometry but impulse oscillometry (IOS)-defined small airway dysfunction (SAD) and small airway reversibility (SAR) after bronchodilator inhalation. Participants were randomized 1:1 to receive extrafine BDP/FOR plus as-needed salbutamol, or as-needed salbutamol alone, for 4 weeks. Symptom score (Asthma Control Test), spirometry, IOS parameters, type 2 inflammatory biomarkers (FeNO, blood eosinophils, IgE), and rescue medication use were assessed before and after treatment.
Read the detailed description
Symptomatic patients with asthma-like respiratory symptoms may have preserved conventional spirometry (FEV1/FVC ≥ 0.7, FVC ≥ 80% predicted, negative bronchodilator reversibility) yet still exhibit small airway dysfunction detectable only by impulse oscillometry (IOS). This prospective, single-center, open-label, randomized controlled trial enrolled adult patients (≥20 years) with chronic respiratory symptoms ≥8 weeks, preserved spirometry, IOS-defined SAD, and small airway reversibility (SAR), defined as AX > 0.44 kPa/L with a post-bronchodilator reduction in AX ≥35% after salbutamol 400 µg. Eligible participants were randomized 1:1 to receive either extrafine beclomethasone dipropionate/formoterol fumarate (100 mcg/6 mcg, 1 puff twice daily) plus as-needed salbutamol, or as-needed salbutamol alone (100 mcg, up to 200 mcg per use, maximum 4 times daily), for 4 weeks. Outcomes assessed before and after treatment included Asthma Control Test (ACT) score, spirometry (FEV1, FVC), IOS parameters (R5-R20, resonant frequency [Fres], reactance at 5Hz [X5], reactance area [AX]) with pre/post-bronchodilator change, fractional exhaled nitric oxide (FeNO), blood eosinophil count, serum total IgE, and frequency of rescue SABA use. The primary endpoint was the between-group difference in change of IOS parameters after 4 weeks of treatment; secondary endpoints included changes in symptom score, conventional spirometry, and inflammatory biomarkers, as well as treatment safety and tolerability.
- Conditions
- Small Airway Dysfunction
- Being tested
- Beclomethasone dipropionate/formoterol fumarate (extrafine), Salbutamol
- Keywords
- Impulse oscillometry, Small airway reversibility, Extrafine inhaled corticosteroid, Type 2 inflammation, Fractional exhaled nitric oxide, Preserved spirometry
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beclomethasone dipropionate/formoterol fumarate (extrafine)Drug
Extrafine fixed-dose combination inhaler, 100 mcg beclomethasone dipropionate + 6 mcg formoterol fumarate dihydrate per actuation, 1 puff twice daily for 4 weeks.
Arm(s): Extrafine BDP/FOR + as-needed SABA
SalbutamolDrug
Short-acting β2-agonist metered-dose inhaler, 100 mcg/actuation, used as needed for symptom relief (max 200 mcg/use, max 4 times/day).
Arm(s): As-needed SABA alone
| Study group | Role | What they receive |
|---|---|---|
| Extrafine BDP/FOR + as-needed SABA | Experimental | Extrafine beclomethasone dipropionate 100 mcg/formoterol fumarate dihydrate 6 mcg (Foster®), 1 inhalation twice daily for 4 weeks, plus salbutamol 100 mcg as needed (max 200 mcg/use, max 4 times/day).
Assigned Intervention: Drug: Beclomethasone dipropionate/formoterol fumarate (extrafine) Receives: Drug: Beclomethasone dipropionate/formoterol fumarate (extrafine); Drug: Salbutamol |
| As-needed SABA alone | Active comparator | Salbutamol 100 mcg as needed (max 200 mcg/use, max 4 times/day) for 4 weeks, without ICS/LABA.
Assigned Intervention: Drug: Salbutamol Receives: Drug: Salbutamol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Airway Resistance Difference (R5-R20) After 4 Weeks of Treatment
Between-group difference in change from baseline in the difference between resistance at 5 Hz and resistance at 20 Hz (R5-R20), measured by impulse oscillometry. Unit of measure: kPa/(L/s).
Measured: Baseline (Visit 1) and Week 4 (Visit 2)
Change in Resonant Frequency (Fres) After 4 Weeks of Treatment
Between-group difference in change from baseline in resonant frequency (Fres), measured by impulse oscillometry. Unit of measure: Hz.
Measured: Baseline (Visit 1) and Week 4 (Visit 2)
Change in Reactance at 5 Hz (X5) After 4 Weeks of Treatment
Between-group difference in change from baseline in reactance at 5 Hz (X5), measured by impulse oscillometry. Unit of measure: kPa/(L/s).
Measured: Baseline (Visit 1) and Week 4 (Visit 2)
Change in Reactance Area (AX) After 4 Weeks of Treatment
Between-group difference in change from baseline in reactance area (AX), measured by impulse oscillometry. Unit of measure: kPa/L.
Measured: Baseline (Visit 1) and Week 4 (Visit 2)
Secondary outcomes (5)
Change in Asthma Control Test (ACT) Score
Change in Asthma Control Test (ACT) Score. The ACT is a 5-item scale (score range 5-25), with higher scores indicating better asthma symptom control.
Measured: Baseline and Week 4
Change in Fractional Exhaled Nitric Oxide (FeNO)
Measured: Baseline and Week 4
Change in Spirometric Parameters (FEV1, FVC)
Measured: Baseline and Week 4
Change in Type 2 Inflammatory Biomarkers (Blood Eosinophil Count, Serum Total IgE)
Measured: Baseline and Week 4
Frequency of Rescue SABA Use
Puffs of salbutamol per day, number of days requiring rescue medication, and number of weeks with SABA use ≥2 puffs/week during the 4-week treatment period.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2026
- Study start12 Aug 2021
- Primary completion29 Nov 2024
- Study completion29 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Small Airway DysfunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yi-Han Hsiao
- Sponsor type
- Other government
- Collaborators
- Kaohsiung Chest Disease Prevention and Health Education Association
- Responsible party
- Sponsor-investigator, Yi-Han Hsiao, Taipei Veterans General Hospital, Taiwan
- Investigators
- Yi-Han Hsiao, MD, PhD, Principal investigator, Taipei Veterans General Hospital, Department of Chest Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07809555
- Sponsor's protocol ID
- TVGH No.: 2021-06-004C
- Status last verified
- Sep 2026
- First submitted
- 3 Sep 2026
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Extrafine Inhaled Corticosteroid/Long-Acting β2-Agonist Therapy on Small Airway Dysfunction and Type 2 Inflammatory Biomarkers in Symptomatic Patients With Preserved Spirometry
- ClinicalTrials.gov ID
- NCT07809555
- Acronym / sponsor ID
- TVGH No.: 2021-06-004C
- Conditions
- Small Airway Dysfunction
- Keywords
- Impulse oscillometry, Small airway reversibility, Extrafine inhaled corticosteroid, Type 2 inflammation, Fractional exhaled nitric oxide, Preserved spirometry
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Yi-Han HsiaoOther government
- Collaborators
- Kaohsiung Chest Disease Prevention and Health Education Association
- Study start
- 12 Aug 2021 (actual)
- Primary completion
- 29 Nov 2024 (actual)
- Study completion
- 29 Nov 2024 (actual)
- First posted
- 9 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates whether 4 weeks of extrafine inhaled corticosteroid/long-acting β2-agonist (beclomethasone dipropionate/formoterol fumarate, BDP/FOR) therapy improves clinical, physiological, and type 2 inflammatory outcomes compared with as-needed short-acting β2-agonist (SABA, salbutamol) alone in symptomatic patients who have preserved conventional spirometry but impulse oscillometry (IOS)-defined small airway dysfunction (SAD) and small airway reversibility (SAR) after bronchodilator inhalation. Participants were randomized 1:1 to receive extrafine BDP/FOR plus as-needed salbutamol, or as-needed salbutamol alone, for 4 weeks. Symptom score (Asthma Control Test), spirometry, IOS parameters, type 2 inflammatory biomarkers (FeNO, blood eosinophils, IgE), and rescue medication use were assessed before and after treatment.
Detailed description
Symptomatic patients with asthma-like respiratory symptoms may have preserved conventional spirometry (FEV1/FVC ≥ 0.7, FVC ≥ 80% predicted, negative bronchodilator reversibility) yet still exhibit small airway dysfunction detectable only by impulse oscillometry (IOS). This prospective, single-center, open-label, randomized controlled trial enrolled adult patients (≥20 years) with chronic respiratory symptoms ≥8 weeks, preserved spirometry, IOS-defined SAD, and small airway reversibility (SAR), defined as AX > 0.44 kPa/L with a post-bronchodilator reduction in AX ≥35% after salbutamol 400 µg. Eligible participants were randomized 1:1 to receive either extrafine beclomethasone dipropionate/formoterol fumarate (100 mcg/6 mcg, 1 puff twice daily) plus as-needed salbutamol, or as-needed salbutamol alone (100 mcg, up to 200 mcg per use, maximum 4 times daily), for 4 weeks. Outcomes assessed before and after treatment included Asthma Control Test (ACT) score, spirometry (FEV1, FVC), IOS parameters (R5-R20, resonant frequency [Fres], reactance at 5Hz [X5], reactance area [AX]) with pre/post-bronchodilator change, fractional exhaled nitric oxide (FeNO), blood eosinophil count, serum total IgE, and frequency of rescue SABA use. The primary endpoint was the between-group difference in change of IOS parameters after 4 weeks of treatment; secondary endpoints included changes in symptom score, conventional spirometry, and inflammatory biomarkers, as well as treatment safety and tolerability.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Extrafine BDP/FOR + as-needed SABA | Experimental | Drug: Beclomethasone dipropionate/formoterol fumarate (extrafine), Drug: SalbutamolExtrafine beclomethasone dipropionate 100 mcg/formoterol fumarate dihydrate 6 mcg (Foster®), 1 inhalation twice daily for 4 weeks, plus salbutamol 100 mcg as needed (max 200 mcg/use, max 4 times/day). Assigned Intervention: Drug: Beclomethasone dipropionate/formoterol fumarate (extrafine) |
| As-needed SABA alone | Active comparator | Drug: SalbutamolSalbutamol 100 mcg as needed (max 200 mcg/use, max 4 times/day) for 4 weeks, without ICS/LABA. Assigned Intervention: Drug: Salbutamol |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥20 years
- Chronic respiratory symptoms (cough, sputum, chest tightness, dyspnea, or wheezing) for ≥8 weeks
- Preserved spirometry: FEV1/FVC ≥0.7, FVC ≥80% predicted, and negative bronchodilator reversibility (increase in FEV1 or FVC <12% and <200 mL after salbutamol)
- IOS-defined small airway dysfunction and small airway reversibility (SAR): AX >0.44 kPa/L with post-bronchodilator reduction in AX ≥35% after salbutamol inhalation
Key exclusion criteria (13 listed)
- Age <20 years
- Impaired spirometry (FEV1/FVC <0.7, FVC ≤80% predicted, or positive bronchodilator reversibility)
- Absence of SAD or lack of significant SAR
- Respiratory symptoms absent or <8 weeks
- Acute respiratory condition within 4 weeks before enrollment (upper/lower respiratory tract infection, acute exacerbation, pneumonia requiring antibiotics, ED visit or hospitalization)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Beclomethasone dipropionate/formoterol fumarate (extrafine)Extrafine fixed-dose combination inhaler, 100 mcg beclomethasone dipropionate + 6 mcg formoterol fumarate dihydrate per actuation, 1 puff twice daily for 4 weeks. Arm(s): Extrafine BDP/FOR + as-needed SABA | Drug | Extrafine BDP/FOR + as-needed SABA |
| SalbutamolShort-acting β2-agonist metered-dose inhaler, 100 mcg/actuation, used as needed for symptom relief (max 200 mcg/use, max 4 times/day). Arm(s): As-needed SABA alone | Drug | As-needed SABA alone, Extrafine BDP/FOR + as-needed SABA |
Primary outcome
Change in Airway Resistance Difference (R5-R20) After 4 Weeks of Treatment
Time frame: Baseline (Visit 1) and Week 4 (Visit 2)
Between-group difference in change from baseline in the difference between resistance at 5 Hz and resistance at 20 Hz (R5-R20), measured by impulse oscillometry. Unit of measure: kPa/(L/s).
Change in Resonant Frequency (Fres) After 4 Weeks of Treatment
Time frame: Baseline (Visit 1) and Week 4 (Visit 2)
Between-group difference in change from baseline in resonant frequency (Fres), measured by impulse oscillometry. Unit of measure: Hz.
Change in Reactance at 5 Hz (X5) After 4 Weeks of Treatment
Time frame: Baseline (Visit 1) and Week 4 (Visit 2)
Between-group difference in change from baseline in reactance at 5 Hz (X5), measured by impulse oscillometry. Unit of measure: kPa/(L/s).
Change in Reactance Area (AX) After 4 Weeks of Treatment
Time frame: Baseline (Visit 1) and Week 4 (Visit 2)
Between-group difference in change from baseline in reactance area (AX), measured by impulse oscillometry. Unit of measure: kPa/L.
5 secondary outcomes
Change in Asthma Control Test (ACT) Score
Time frame: Baseline and Week 4
Change in Fractional Exhaled Nitric Oxide (FeNO)
Time frame: Baseline and Week 4
Change in Spirometric Parameters (FEV1, FVC)
Time frame: Baseline and Week 4
Change in Type 2 Inflammatory Biomarkers (Blood Eosinophil Count, Serum Total IgE)
Time frame: Baseline and Week 4
Frequency of Rescue SABA Use
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yi-Han Hsiao, MD, PhD principal investigator
Taipei Veterans General Hospital, Department of Chest Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Beclomethasone dipropionate/formoterol fumarate (extrafine) and Salbutamol in people with Small Airway Dysfunction, run by Yi-Han Hsiao at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Airway Resistance Difference (R5-R20) After 4 Weeks of Treatment (time frame: Baseline (Visit 1) and Week 4 (Visit 2)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.