A Mechanistic Study of Inhaled Nitric Oxide in COPD

Not Applicable

Recruiting

• Conditions: Chronic Obstructive Pulmonary Disease; Pulmonary Hypertension
• Interventions: Device: Nitric Oxide Generation and Delivery System

• Registration Number: NCT05785195
• Lead Sponsor: Ting YANG

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-17
• Study Start: 2023-03-14
• Study First Submitted QC: 2023-03-14
• Study First Posted: 2023-03-27
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-12
• Last Update Posted: 2023-05-15
• Primary Completion: 2023-12-31
• Study Completion: 2024-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Inhaled Nitric Oxide (iNO)	Nitric Oxide Generation and Delivery System	iNO 20ppm，≥8 hours/day for 3 days

Primary Outcome Measures

Name	Time	Method
Pulmonary arterial systolic pressure (sPAP)	Baseline, Day 3	Change in sPAP from Baseline after treatment with iNO, measured by echocardiogram
Ventilation-perfusion ratio	Baseline, Minutes 30	Change in ventilation-perfusion ratio (V/Q) from Baseline after treatment with iNO, measured by pulmonary ventilation/perfusion imaging
Tricuspid regurgitation velocity (TRV)	Baseline, Day 3	Change in TRV from Baseline after treatment with iNO, measured by echocardiogram

Secondary Outcome Measures

Name	Time	Method
Pulmonary function: Forced vital capacity （FVC）	Baseline, Day 3	Change in FVC from Baseline after treatment with iNO
Pulmonary function: FEV1/FVC	Baseline, Day 3	Change in ratio of FEV1 and FVC (FEV1/FVC) from Baseline after treatment with iNO
Cardiopulmonary Exercise Test: Anaerobic threshold（AT）	Baseline, Day 3	Change in AT from Baseline after treatment with iNO
Pulmonary function: Diffusion lung capacity for carbon monoxide（DLCO)	Baseline, Day 3	Change in DLCO from Baseline after treatment with iNO
Cardiopulmonary Exercise Test: Minute ventilation-to-carbon dioxide output（VE/VCO2）	Baseline, Day 3	Change in VE/VCO2 from Baseline after treatment with iNO
Arterial blood gas: Arterial partial pressure of carbon dioxide (PaCO2)	Baseline, Day 3	Change in PaCO2 from Baseline after treatment with iNO
Life quality and symtom severity questionnaires: Modified Medical Research Council (mMRC) Dyspnea Scale	Baseline, Day 3	Change in (mMRC) Dyspnea Scale scores (0-4 scores, higher scores mean a worse outcome) from Baseline after treatment with iNO
Adverse events	Baseline up to Day 3	Incidence of adverse events = Number of subjects with adverse events/Total number of subjects in treatment×100%
Pulmonary function:Forced expiratory volume in 1 second（FEV1）	Baseline, Day 3	Change in FEV1 from Baseline after treatment with iNO
Percutaneous arterial oxygen saturation (SpO2)	Baseline, Day 3	Change in SpO2 from Baseline after treatment with iNO
Cardiopulmonary Exercise Test: Maximal oxygen uptake（VO2max）	Baseline, Day 3	Change in VO2max from Baseline after treatment with iNO
Six-minute walk distance (6MWD)	Baseline, Day 3	Change in 6MWD from Baseline after treatment with iNO
Arterial blood gas: Alveolar-arterial oxygen partial pressure difference (A-aDO2)	Baseline, Day 3	Change in A-aDO2 from Baseline after treatment with iNO
Life quality and symtom severity questionnaires: COPD assessment test (CAT)	Baseline, Day 3	Change in CAT scores (0-40 scores, higher scores mean a worse outcome) from Baseline after treatment with iNO
Life quality and symtom severity questionnaires: Saint George Respiratory Questionnaire (SGRQ)	Baseline, Day 3	Change in SGRQ scores (0-100 scores, higher scores mean a worse outcome) from Baseline after treatment with iNO
Cardiopulmonary Exercise Test: Physiological dead space ventilation (physiological deadspace volume/tidal volume, Vd/Vt)	Baseline, Day 3	Change in Vd/Vt from Baseline after treatment with iNO
Arterial blood gas: Arterial partial pressure of oxygen (PaO2)	Baseline, Day 3	Change in PaO2 from Baseline after treatment with iNO

Trial Locations

Locations (1)

China-Japan Friendship Hospital; 🇨🇳 Beijing, China