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

NCT02546349 | Unknown Phase 4

• 1 other identifier: 140420
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 1

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.

Conditions

COPD

Keywords

chronic obstructive pulmonary disease; airway inflammation; eosinophilic airway inflammation; exhaled nitric oxide

Outcome Measures

Primary Outcomes (1)

• Changes of eNO level

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

Secondary Outcomes (7)

• 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

Study Arms (4)

high eNO: ICS/LABA

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.

Drug: fluticasone/salmeterol, tiotropium

high eNO: LAMA

ACTIVE COMPARATOR

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

Low eNO: ICS/LABA

EXPERIMENTAL

patients with eNO \< 23.5 ppb, receive fluticasone/salmeterol 250/25 mcg/puff, 2 puffs bid

Drug: fluticasone/salmeterol, tiotropium

Low eNO: LAMA

ACTIVE COMPARATOR

patients with eNO \< 23.5 ppb, receive tiotropium 2 inhalations 2.5 mcg/inhalation, once daily

Drug: fluticasone/salmeterol, tiotropium

Interventions

fluticasone/salmeterol, tiotropium DRUG

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.

Also known as: seretide evohaler 250, spiriva respimat

Low eNO: ICS/LABA; Low eNO: LAMA; high eNO: ICS/LABA; high eNO: LAMA

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female outpatients aged from 40 to 90 years
• Current or ex-smoker, with smoking history ≧ 20 pack- years
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Taipei Veterans General Hospital, Taiwan: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Taipei Veterans General Hospital

Taipei, Taiwan, 886, Taiwan

Location

Related Publications (1)

• Su KC, Ko HK, Hsiao YH, Chou KT, Chen YW, Yu WK, Pan SW, Feng JY, Perng DW. Fractional Exhaled Nitric Oxide Guided-Therapy in Chronic Obstructive Pulmonary Disease: A Stratified, Randomized, Controlled Trial. Arch Bronconeumol. 2022 Aug;58(8):601-610. doi: 10.1016/j.arbres.2021.11.013. Epub 2021 Dec 18. English, Spanish.

  PMID: 35312525 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Fluticasone; Salmeterol Xinafoate; Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• Diahn-Warng S Perng, PhD

  Taipei Veterans General Hospital, Taiwan

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2015
• First Posted: September 10, 2015
• Study Start: July 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2016
• Last Updated: September 10, 2015

Record last verified: 2015-09

Locations

TW (1)