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

September 9, 2015 updated by: Taipei Veterans General Hospital, Taiwan

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

143

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei City, Taiwan, 886
        • Taipei Veterans General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: high eNO: ICS/LABA
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.
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.
Other Names:
  • seretide evohaler 250
  • spiriva respimat
Active Comparator: high eNO: LAMA
patients with eNO >=23.5 ppb, receive long acting muscarinic antagonist (LAMA) of tiotropium 2 inhalations 2.5 mcg/inhalation, once daily
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.
Other Names:
  • seretide evohaler 250
  • spiriva respimat
Experimental: Low eNO: ICS/LABA
patients with eNO < 23.5 ppb, receive fluticasone/salmeterol 250/25 mcg/puff, 2 puffs bid
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.
Other Names:
  • seretide evohaler 250
  • spiriva respimat
Active Comparator: Low eNO: LAMA
patients with eNO < 23.5 ppb, receive tiotropium 2 inhalations 2.5 mcg/inhalation, once daily
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.
Other Names:
  • seretide evohaler 250
  • spiriva respimat

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Changes of eNO level
Time Frame: Changes of eNO level (ppb) from baseline at 12 weeks
Changes of eNO level (ppb) from baseline at 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes of lung function parameters (FEV1, FVC)
Time Frame: Changes of lung function parameters (FEV1, FVC) from baseline at 12 weeks
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 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 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 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
COPD assessment test (CAT)
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 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
Changes of MMP-9 levle (ug/ml) in induced sputum from baseline at 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taipei Veterans General Hospital, Taiwan

Collaborators

GlaxoSmithKline

Investigators

  • Study Chair: Diahn-Warng S Perng, PhD, Taipei Veterans General Hospital, Taiwan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2014

Primary Completion (Anticipated)

December 1, 2015

Study Completion (Anticipated)

January 1, 2016

Study Registration Dates

First Submitted

February 25, 2015

First Submitted That Met QC Criteria

September 9, 2015

First Posted (Estimate)

September 10, 2015

Study Record Updates

Last Update Posted (Estimate)

September 10, 2015

Last Update Submitted That Met QC Criteria

September 9, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 140420

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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