Exhaled NO Based Treatment of Chronic Obstructive Pulmonary Disease (COPD), ICS/LABA Versus LAMA

Phase 4

• Conditions: COPD
• Interventions: Drug: fluticasone/salmeterol, tiotropium

• Registration Number: NCT02546349
• Lead Sponsor: Taipei Veterans General Hospital, Taiwan

Brief Summary

It is recognized that eosinophilic airway inflammation is more likely respond to steroid treatment. However, in real-world practice, it is difficult to routinely assess airway inflammation using sputum induction because of technical and facility requirement. COPD (chronic obstructive pulmonary disease) is a heterogeneous disease and it remains a great challenge to identify patients who have eosinophilic airway inflammation and respond to steroid treatment well. A recent study demonstrated elevated plasma D-dimer was associated with acute inflammation and a significant predictor of pulmonary embolism in COPD exacerbated patients. D-dimer may potentially act as a marker of inflammation and a predictor of cardiovascular event in COPD patients. The investigators preliminary study demonstrated that exhaled nitric oxide (eNO) \> 23.5 ppb is a good surrogate marker to predict eosinophilic airway inflammation in COPD patients who were newly diagnosed or untreated for at least 3 months. There were significant correlations among sputum eosinophils, eNO and serum total immunoglobulin E (IgE). Particularly, eNO predicted sputum eosinophilia (\> 3%) in COPD at a sensitivity and specificity of 62% and 71% respectively. Herein, the investigators test the hypothesis that eNO may act as a biomarker to determine treatment option for COPD.

Detailed Description

Eligible COPD patients (newly diagnosed or untreated for at least 3 months) will be enrolled at out-patient clinic after consenting by participants. Upon enrollment, exhaled NO (eNO) will be measured and patients will be categorized into 2 groups according to eNO levels: either high exhaled NO (greater than or equal to 23.5 ppb) or low eNO (\< 23.5 ppb) group. In each group, patients will be randomized to receive either 2 inhalations of fluticasone/salmeterol 250/25 mcg/ pudd twice daily or 2 inhalations of tiotropium 2.5 mcg/inhalation for 12 weeks and followed at scheduled visits. Testing outcome measures include eNO, lung function, different count and mediators in induced sputum, and which will be tested as the following timings: before (baseline, week 0), and after treatment (week 4 and week 12). Rescue medication and drug compliance will be record.

Study Timeline

• Study Start: 2014-07
• Study First Submitted: 2015-02-25
• Status Verified: 2015-09
• Study First Submitted QC: 2015-09-09
• Last Update Submitted: 2015-09-09
• Study First Posted: 2015-09-10
• Last Update Posted: 2015-09-10
• Primary Completion: 2015-12
• Study Completion: 2016-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 143

Inclusion Criteria

1. Male or female outpatients aged from 40 to 90 years
2. Current or ex-smoker, with smoking history ≧ 20 pack- years
3. Newly diagnosed or untreated (at least 3 months) COPD patients (forced expiratory volume in first second (FEV1)/forced vital capacity (FVC) < 70%) with post-bronchodilator FEV1 < 80 % predicted value.

Exclusion Criteria

1. Concurrent allergic rhinitis, eczema, and asthma.
2. Clinically overt bronchiectasis, lung cancer, active tuberculosis, or other known specific pulmonary disease.
3. A chest X-ray indicating diagnosis other than COPD that might interfere with the study.
4. Major disease abnormalities are uncontrolled on therapy.
5. Alcohol or medication abuse.
6. Patients had lower respiratory tract infections or received systemic steroid in the 4 weeks prior to the commencement of study.
7. Women with childbearing potential during the period of trial.
8. Unable or unwilling to comply with all protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
high eNO: ICS/LABA	fluticasone/salmeterol, tiotropium	patients with eNO \>=23.5 ppb, receive inhaled corticosteroid (ICS)/long-acting beta2 agonist (ICS/LABA) of fluticasone/salmeterol 250/25 mcg/puff, 2 puffs bid.
high eNO: LAMA	fluticasone/salmeterol, tiotropium	patients with eNO \>=23.5 ppb, receive long acting muscarinic antagonist (LAMA) of tiotropium 2 inhalations 2.5 mcg/inhalation, once daily
Low eNO: ICS/LABA	fluticasone/salmeterol, tiotropium	patients with eNO \< 23.5 ppb, receive fluticasone/salmeterol 250/25 mcg/puff, 2 puffs bid
Low eNO: LAMA	fluticasone/salmeterol, tiotropium	patients with eNO \< 23.5 ppb, receive tiotropium 2 inhalations 2.5 mcg/inhalation, once daily

Primary Outcome Measures

Name	Time	Method
Changes of eNO level	Changes of eNO level (ppb) from baseline at 12 weeks

Secondary Outcome Measures

Name	Time	Method
Changes of lung function parameters (FEV1, FVC)	Changes of lung function parameters (FEV1, FVC) from baseline at 12 weeks
Changes of serum level of IgE	Changes of serum level of IgE (IU/ml) from baseline at 12 weeks
Changes of serum level of matrix metalloproteinase (MMP)-9	Changes of serum level of MMP-9 (ng/ml) from baseline at 12 weeks
Changes of serum level of D-dimer	Changes of serum level of D-dimer (ug/ml) from baseline at 12 weeks
Changes of scales of life quality questionnaire	Changes of scales of life quality questionnaire from baseline at 12 weeks	COPD assessment test (CAT)
Changes of proportion of cell counts in induced sputum	Changes of proportion of cell counts in induced sputum from baseline at 12 weeks
Changes of MMP-9 level in induced sputum	Changes of MMP-9 levle (ug/ml) in induced sputum from baseline at 12 weeks

Trial Locations

Locations (1)

Taipei Veterans General Hospital; 🇨🇳 Taipei City, Taiwan