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

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ClinicalTrials.gov Identifier: NCT02546349
Recruitment Status : Unknown
Verified September 2015 by Taipei Veterans General Hospital, Taiwan.
Recruitment status was:  Active, not recruiting
First Posted : September 10, 2015
Last Update Posted : September 10, 2015
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
COPD Drug: fluticasone/salmeterol, tiotropium Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 143 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : July 2014
Estimated Primary Completion Date : December 2015
Estimated Study Completion Date : January 2016

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Changes of eNO level [ Time Frame: Changes of eNO level (ppb) from baseline at 12 weeks ]

Secondary Outcome Measures :
  1. Changes of lung function parameters (FEV1, FVC) [ Time Frame: Changes of lung function parameters (FEV1, FVC) from baseline at 12 weeks ]
  2. Changes of serum level of IgE [ Time Frame: Changes of serum level of IgE (IU/ml) from baseline at 12 weeks ]
  3. 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 ]
  4. Changes of serum level of D-dimer [ Time Frame: Changes of serum level of D-dimer (ug/ml) from baseline at 12 weeks ]
  5. 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)

  6. 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 ]
  7. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02546349


Locations
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Taiwan
Taipei Veterans General Hospital
Taipei City, Taiwan, 886
Sponsors and Collaborators
Taipei Veterans General Hospital, Taiwan
GlaxoSmithKline
Investigators
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Study Chair: Diahn-Warng S Perng, PhD Taipei Veterans General Hospital, Taiwan

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Responsible Party: Taipei Veterans General Hospital, Taiwan
ClinicalTrials.gov Identifier: NCT02546349     History of Changes
Other Study ID Numbers: 140420
First Posted: September 10, 2015    Key Record Dates
Last Update Posted: September 10, 2015
Last Verified: September 2015
Keywords provided by Taipei Veterans General Hospital, Taiwan:
chronic obstructive pulmonary disease
airway inflammation
eosinophilic airway inflammation
exhaled nitric oxide
Additional relevant MeSH terms:
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Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
Fluticasone
Nitric Oxide
Tiotropium Bromide
Salmeterol Xinafoate
Fluticasone-Salmeterol Drug Combination
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Free Radical Scavengers
Antioxidants
Endothelium-Dependent Relaxing Factors