Extrafine ICS/LABA Versus As-Needed SABA for Small Airway Dysfunction in Symptomatic Patients With Preserved Spirometry

NCT07809555 | Completed Phase 4

• 1 other identifier: TVGH No.: 2021-06-004C
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Small Airway Dysfunction

Keywords

Impulse oscillometry; Small airway reversibility; Extrafine inhaled corticosteroid; Type 2 inflammation; Fractional exhaled nitric oxide; Preserved spirometry

Outcome Measures

Primary Outcomes (4)

• 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).

  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.

  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).

  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.

  Baseline (Visit 1) and Week 4 (Visit 2)

Secondary Outcomes (5)

• Change in Asthma Control Test (ACT) Score

  Baseline and Week 4

• Change in Fractional Exhaled Nitric Oxide (FeNO)

  Baseline and Week 4

• Change in Spirometric Parameters (FEV1, FVC)

  Baseline and Week 4

• Change in Type 2 Inflammatory Biomarkers (Blood Eosinophil Count, Serum Total IgE)

  Baseline and Week 4

• Frequency of Rescue SABA Use

  4 weeks

Study Arms (2)

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)

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

Drug: Salbutamol

Interventions

Salbutamol DRUG

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

As-needed SABA alone; Extrafine BDP/FOR + as-needed SABA

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

Extrafine BDP/FOR + as-needed SABA

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Yi-Han Hsiao: lead
• Kaohsiung Chest Disease Prevention and Health Education Association: collaborator

Study Sites (1)

Taipei Veterans General Hospital, Department of Chest Medicine

Taipei, 11217, Taiwan

Location

MeSH Terms

Interventions

Beclomethasone; Formoterol Fumarate; Albuterol

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Study Officials

• Yi-Han Hsiao, MD, PhD

  Taipei Veterans General Hospital, Department of Chest Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open-label design; participants and investigators were not blinded to treatment allocation due to differing inhaler devices.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: September 3, 2026
• First Posted: September 9, 2026
• Study Start: August 12, 2021
• Primary Completion: November 29, 2024
• Study Completion: November 29, 2024
• Last Updated: September 24, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)