Clinical trial NCT05785195: A Mechanistic Study of Inhaled Nitric Oxide in COPD
Official title: Study on the Mechanism of Inhaled Nitric Oxide in the Treatment of Patients With Chronic Obstructive Pulmonary Disease (COPD) Complicated With Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Pulmonary Hypertension
Lead sponsor: China-Japan Friendship Hospital
Sponsor class: OTHER
Collaborators: name: Novlead Inc.
First posted: 2023-03-27
Enrollment: 15
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: There is a lack of effective treatments for chronic obstructive pulmonary disease (COPD) complicated with pulmonary hypertension. Previous studies have found that inhaled nitric oxide (iNO) can reduce pulmonary artery pressure and improve exercise capacity in COPD with pulmonary hypertension patients. However, the specific mechanism is unclear. The study aims to evaluate pulmonary ventilation/perfusion, pulmonary artery pressure, oxygenation, symptoms and quality of life in COPD with pulmonary hypertension patients after short-term treatment with iNO. Observing a series of pathophysiological changes caused by the treatment of pulmonary hypertension with iNO in COPD, the investigators hope to provide new theoretical basis and research ideas.


Eligibility criteria: Inclusion Criteria:

1. Age ≥ 40 years, ≤ 75 years
2. Currently smoking or former smokers with at least 10 pack-years of tobacco cigarette smoking history
3. Diagnosis of moderate and severe COPD by the Global initiative for chronic Obstructive Lung Disease (GOLD) 2022 criteria: A post-bronchodilatory forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) \< 0.7, and 30%\< FEV1 \< 80% predicted
4. Echocardiogram with technical adequacy demonstrating with Pulmonary Hypertension: Tricuspid regurgitation velocity (TRV) \> 2.8 m/s or pulmonary arterial systolic pressure (sPAP) ≥38mmHg
5. Signed informed consent prior to the initiation of any study mandated procedures or assessments

Exclusion Criteria:

1. Experienced an exacerbation requiring start of or increase in systemic oral corticosteroid therapy during the last month
2. Treatment with antibiotics
3. Respiratory failure requiring supplemental oxygen therapy
4. A diagnosis of Interstitial lung disease, asthma, tuberculosis, bronchiectasis, pneumonia, lung cancer, pulmonary embolism, or other non-COPD respiratory disease
5. Any history of lung resection
6. Left ventricular dysfunction: left ventricular ejection fraction (LVEF) \< 40%
7. Clinically significant valvular heart disease, including aortic valvular disease (moderate or greater aortic stenosis or regurgitation) and/or mitral valve disease (moderate or greater mitral stenosis or regurgitation), or status post mitral valve replacement
8. Use within 30 days of screening or current use of approved PH medications such as sildenafil, bosentan or prostacyclines
9. Neuromuscular disease or musculoskeletal injuries that unable to complete exercise trials
10. Use of investigational drugs or devices within 30 days prior to enrollment into the study
11. Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study

Primary outcomes:
measure: Ventilation-perfusion ratio
timeFrame: Baseline, Minutes 30
measure: Tricuspid regurgitation velocity (TRV)
timeFrame: Baseline, Day 3
measure: Pulmonary arterial systolic pressure (sPAP)
timeFrame: Baseline, Day 3
Secondary outcomes:
measure: Percutaneous arterial oxygen saturation (SpO2)
timeFrame: Baseline, Day 3
measure: Pulmonary function:Forced expiratory volume in 1 second（FEV1）
timeFrame: Baseline, Day 3
measure: Pulmonary function: Forced vital capacity （FVC）
timeFrame: Baseline, Day 3
measure: Pulmonary function: FEV1/FVC
timeFrame: Baseline, Day 3
measure: Pulmonary function: Diffusion lung capacity for carbon monoxide（DLCO)
timeFrame: Baseline, Day 3
measure: Cardiopulmonary Exercise Test: Maximal oxygen uptake（VO2max）
timeFrame: Baseline, Day 3
measure: Cardiopulmonary Exercise Test: Anaerobic threshold（AT）
timeFrame: Baseline, Day 3
measure: Cardiopulmonary Exercise Test: Minute ventilation-to-carbon dioxide output（VE/VCO2）
timeFrame: Baseline, Day 3
measure: Cardiopulmonary Exercise Test: Physiological dead space ventilation (physiological deadspace volume/tidal volume, Vd/Vt)
timeFrame: Baseline, Day 3
measure: Six-minute walk distance (6MWD)
timeFrame: Baseline, Day 3
measure: Arterial blood gas: Arterial partial pressure of oxygen (PaO2)
timeFrame: Baseline, Day 3
measure: Arterial blood gas: Arterial partial pressure of carbon dioxide (PaCO2)
timeFrame: Baseline, Day 3
measure: Arterial blood gas: Alveolar-arterial oxygen partial pressure difference (A-aDO2)
timeFrame: Baseline, Day 3
measure: Life quality and symtom severity questionnaires: COPD assessment test (CAT)
timeFrame: Baseline, Day 3
measure: Life quality and symtom severity questionnaires: Modified Medical Research Council (mMRC) Dyspnea Scale
timeFrame: Baseline, Day 3
measure: Life quality and symtom severity questionnaires: Saint George Respiratory Questionnaire (SGRQ)
timeFrame: Baseline, Day 3
measure: Adverse events
timeFrame: Baseline up to Day 3
Other outcomes:
Locations:
city: Beijing
country: China
facility: China-Japan Friendship Hospital
Study officials:
References: