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

COPD Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02546349
• Other study ID #: 140420
• Status: Active, not recruiting
• Phase: Phase 4
• First received: February 25, 2015
• Last updated: September 9, 2015
• Start date: July 2014
• Est. completion date: January 2016

Study information

• Verified date: September 2015
• Source: Taipei Veterans General Hospital, Taiwan
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 143
• Est. completion date: January 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 90 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• COPD
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• fluticasone/salmeterol, tiotropium
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.

Locations

Country	Name	City	State
Taiwan	Taipei Veterans General Hospital	Taipei City

Sponsors (2)

Lead Sponsor	Collaborator
Taipei Veterans General Hospital, Taiwan	GlaxoSmithKline

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of eNO level		Changes of eNO level (ppb) from baseline at 12 weeks	No
Secondary	Changes of lung function parameters (FEV1, FVC)		Changes of lung function parameters (FEV1, FVC) from baseline at 12 weeks	No
Secondary	Changes of serum level of IgE		Changes of serum level of IgE (IU/ml) from baseline at 12 weeks	No
Secondary	Changes of serum level of matrix metalloproteinase (MMP)-9		Changes of serum level of MMP-9 (ng/ml) from baseline at 12 weeks	No
Secondary	Changes of serum level of D-dimer		Changes of serum level of D-dimer (ug/ml) from baseline at 12 weeks	No
Secondary	Changes of scales of life quality questionnaire	COPD assessment test (CAT)	Changes of scales of life quality questionnaire from baseline at 12 weeks	No
Secondary	Changes of proportion of cell counts in induced sputum		Changes of proportion of cell counts in induced sputum from baseline at 12 weeks	No
Secondary	Changes of MMP-9 level in induced sputum		Changes of MMP-9 levle (ug/ml) in induced sputum from baseline at 12 weeks	No