A Clinical Study of Inhaled Nitric Oxide in Moderate-to-Severe Chronic Obstructive Pulmonary Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the influence of exercise capacity and safety of iNO at doses of 10 ppm or 40 ppm for 2 hours per day after continuous treatment for one week, which is of great significance for finding safe and effective methods for treating COPD.

Official Title
-----------------
Efficacy and Safety of Inhaled Nitric Oxide in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease: a Prospective, Single-center Clinical Trial

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Device: Nitric Oxide Generation and Delivery System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 40 years, ≤ 75 years; Previous smoking history ≥ 10 pack-years, and had stopped smoking for one month before study entry; Met the diagnosis criteria of moderate and severe COPD: a post-bronchodilator FEV1/FVC < 0.7, and 30%< FEV1 < 80% predicted; Signed informed consent and performed all the study mandated procedures. Exclusion Criteria: Pregnant or lactating women; Current or recent month user of nicotine-like substances (including nicotine patches, etc.); A diagnosis of asthma or other non-COPD respiratory disease, in the opinion of the Investigator; Lack of patency of nares upon physical examination; Experienced during the last month an exacerbation requiring start of or increase in systemic oral corticosteroid therapy; Left ventricular systolic dysfunction: left ventricular ejection fraction (LVEF) < 50%; Clinically significant valvular heart disease, including aortic valvular disease (moderate or severe aortic stenosis or regurgitation) and/or mitral valve disease (moderate or severe mitral stenosis or regurgitation), or status post mitral valve replacement; Use within 30 days of screening or current use of approved pulmonary hypertension medications such as sildenafil, bosentan or prostacyclines; Use of investigational drugs or devices within 30 days prior to enrollment into the study; Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low concentration group<br>inhaled nitric oxide (iNO) 10ppm，≥2 hours/day for 7 days | Device: Nitric Oxide Generation and Delivery System<br>* The Nitric Oxide Generation and Delivery System is used to deliver nitric oxide for inhalation therapy into the inspiratory limb of the patient breathing circuit in a way that provides a constant concentration of nitric oxide (NO), as set by the user, to the patient throughout the inspired breath.<br>|
| Experimental: High concentration group<br>iNO 40ppm，≥2 hours/day for 7 days | Device: Nitric Oxide Generation and Delivery System<br>* The Nitric Oxide Generation and Delivery System is used to deliver nitric oxide for inhalation therapy into the inspiratory limb of the patient breathing circuit in a way that provides a constant concentration of nitric oxide (NO), as set by the user, to the patient throughout the inspired breath.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiopulmonary Exercise Test: Maximal oxygen uptake（VO2max） | Change in VO2max from Baseline after treatment with iNO | Baseline, Day 7 | 
| Cardiopulmonary Exercise Test: Minute ventilation-to-carbon dioxide output（VE/VCO2） | Change in VE/VCO2 from Baseline after treatment with iNO | Baseline, Day 7 | 
| Cardiopulmonary Exercise Test: Borg score | Change in Borg score from Baseline after treatment with iNO | Baseline, Day 7 | 
| Cardiopulmonary Exercise Test: oxygen uptake/work (△VO2/△W) ratio | Change in △VO2/△W ratio from Baseline after treatment with iNO | Baseline, Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary function:Forced expiratory volume in 1 second（FEV1） | Change in FEV1 from Baseline after treatment with iNO | Baseline, Day 7 | 
| Pulmonary function: Forced vital capacity （FVC） | Change in FVC from Baseline after treatment with iNO | Baseline, Day 7 | 
| Pulmonary function：FEV1/FVC | Change in FEV1/FVC from Baseline after treatment with iNO | Baseline, Day 7 | 
| Life quality and symptom severity questionnaires: COPD assessment test (CAT) | Change in CAT scores (0-40 scores, higher scores mean a worse outcome) from Baseline after treatment with iNO | Baseline, Day 7 | 
| Life quality and symptom severity questionnaires: Modified Medical Research Council (mMRC) Dyspnea Scale | Change in (mMRC) Dyspnea Scale scores (0-4 scores, higher scores mean a worse outcome) from Baseline after treatment with iNO | Baseline, Day 7 | 
| Six-minute walk test | Change in exercise capacity from Baseline after treatment with iNO: the distance of six-minute walk test | Baseline, Day 7 | 
| Adverse events | Incidence of adverse events = Number of subjects with adverse events/Total number of subjects in treatment×100% | Baseline up to Day 7 |