Overview

This trial is active, not recruiting.

Condition copd
Treatment fluticasone/salmeterol, tiotropium
Phase phase 4
Sponsor Taipei Veterans General Hospital, Taiwan
Collaborator GlaxoSmithKline
Start date July 2014
End date December 2015
Trial size 143 participants
Trial identifier NCT02546349, 140420

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
fluticasone/salmeterol, tiotropium seretide evohaler 250
In group (either high or low eNO), patients will be randomized to receive either 2 puffs of fluticasone/salmeterol 250/25 mcg/puff twice daily or 2 inhalations of tiotropium respimat 2.5 mcg/inhalation once daily for 12 weeks.
(Active Comparator)
patients with eNO >=23.5 ppb, receive long acting muscarinic antagonist (LAMA) of tiotropium 2 inhalations 2.5 mcg/inhalation, once daily
fluticasone/salmeterol, tiotropium seretide evohaler 250
In group (either high or low eNO), patients will be randomized to receive either 2 puffs of fluticasone/salmeterol 250/25 mcg/puff twice daily or 2 inhalations of tiotropium respimat 2.5 mcg/inhalation once daily for 12 weeks.
(Experimental)
patients with eNO < 23.5 ppb, receive fluticasone/salmeterol 250/25 mcg/puff, 2 puffs bid
fluticasone/salmeterol, tiotropium seretide evohaler 250
In group (either high or low eNO), patients will be randomized to receive either 2 puffs of fluticasone/salmeterol 250/25 mcg/puff twice daily or 2 inhalations of tiotropium respimat 2.5 mcg/inhalation once daily for 12 weeks.
(Active Comparator)
patients with eNO < 23.5 ppb, receive tiotropium 2 inhalations 2.5 mcg/inhalation, once daily
fluticasone/salmeterol, tiotropium seretide evohaler 250
In group (either high or low eNO), patients will be randomized to receive either 2 puffs of fluticasone/salmeterol 250/25 mcg/puff twice daily or 2 inhalations of tiotropium respimat 2.5 mcg/inhalation once daily for 12 weeks.

Primary Outcomes

Measure
Changes of eNO level
time frame: Changes of eNO level (ppb) from baseline at 12 weeks

Secondary Outcomes

Measure
Changes of lung function parameters (FEV1, FVC)
time frame: Changes of lung function parameters (FEV1, FVC) from baseline at 12 weeks
Changes of serum level of IgE
time frame: Changes of serum level of IgE (IU/ml) from baseline at 12 weeks
Changes of serum level of matrix metalloproteinase (MMP)-9
time frame: Changes of serum level of MMP-9 (ng/ml) from baseline at 12 weeks
Changes of serum level of D-dimer
time frame: Changes of serum level of D-dimer (ug/ml) from baseline at 12 weeks
Changes of scales of life quality questionnaire
time frame: Changes of scales of life quality questionnaire from baseline at 12 weeks
Changes of proportion of cell counts in induced sputum
time frame: Changes of proportion of cell counts in induced sputum from baseline at 12 weeks
Changes of MMP-9 level in induced sputum
time frame: Changes of MMP-9 levle (ug/ml) in induced sputum from baseline at 12 weeks

Eligibility Criteria

Male or female participants from 40 years up to 90 years old.

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

Additional Information

Official title The Treatment Effect of Inhaled Corticosteroid and Long-acting beta2 Agonist Combination Versus Long-acting Anti-cholinergic Agent on Stratified COPD Patients Based on the Levels of Exhaled Nitric Oxide
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Taipei Veterans General Hospital, Taiwan.