COPDRB-COPDNCT07160322
Refractory Breathlessness in COPD
An observational study of COPD, run by Seoul National University at 1 site in South Korea.
Trial summary
This study aims to investigate the prognosis and clinical outcomes of patients with chronic obstructive pulmonary disease (COPD) who continue to experience refractory dyspnea despite treatment with long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- COPD
- How many people
- 730 participants
- Where
- 1 siteSouth Korea
- Study dates
- 11 Apr 2024to 31 Dec 2031
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: This study will enroll adult patients (≥ 18 years) diagnosed with chronic obstructive pulmonary disease (COPD) according to the GOLD 2025 criteria, who are receiving combination therapy with long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA). Participants include both patients who continue to experience refractory dyspnea despite treatment and those who show symptomatic improvement. All participants must be able to attend regular outpatient visits and provide written informed consent.
Who may be able to join
- Adults (≥ 18 years) diagnosed with chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2025 criteria:
- Presence of COPD risk factors (e.g., smoking history, occupational exposure, genetic predisposition).
- Typical symptoms such as dyspnea, cough, or sputum production.
- Post-bronchodilator FEV1/FVC < 0.70.
- Regular outpatient follow-up at the respiratory clinic.
- Received LABA/LAMA combination therapy for at least 3 months prior to enrollment.
- Ability and willingness to provide written informed consent.
Who cannot join
- Poor adherence to LABA/LAMA therapy (medication possession rate < 50%) or refusal of treatment.
- Inability or unwillingness to comply with scheduled visits, examinations, or follow-up procedures.
- Presence of severe comorbid conditions expected to significantly affect prognosis, including:
- End-stage diseases with life expectancy < 1 year.
- Terminal malignancies receiving hospice or palliative care.
- Any condition that, in the opinion of the investigator, would interfere with study participation or data reliability.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Seoul National University College of Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center
Seoul, Seoul, 07061
Hyun Woo Lee, 82-10-9755-6172, athrunzara86@snu.ac.kr
About this study
Official title: Prognosis and Clinical Outcomes of Refractory Dyspnea in Chronic Obstructive Pulmonary Disease: Prospective Observational Study
This study aims to investigate the prognosis and clinical outcomes of patients with chronic obstructive pulmonary disease (COPD) who continue to experience refractory dyspnea despite treatment with long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA). The research will prospectively follow a cohort of patients to identify clinical factors, lung function parameters, imaging features, and cardiovascular indicators associated with poor treatment response. By comparing these patients with those who show symptom improvement, the study seeks to determine predictors of exacerbations, lung function decline, and mortality. Findings are expected to guide the development of targeted strategies to improve the management of refractory dyspnea in COPD.
Read the detailed description
The study aims to identify actionable clinical factors and develop predictive models that can enhance personalized management approaches for patients with refractory dyspnea in COPD.
This is a prospective observational cohort study designed to characterize patients with COPD who remain symptomatic despite standard inhaled therapy with LABA/LAMA combination. Participants will be enrolled from outpatient clinics and followed over time to assess changes in respiratory symptoms, lung function, exercise capacity, acute exacerbation frequency, and survival.
Key assessments include:
- Baseline demographic and clinical data (e.g., respiratory symptoms, comorbidities, smoking history).
- Pulmonary function tests (spirometry and lung volumes), exercise capacity evaluations, echocardiography, chest radiographs, and computed tomography (CT).
- Biomarker analysis (blood tests including inflammatory and cardiac markers).
Patients will be classified into two groups:
- Refractory COPD group - Patients with minimal improvement in dyspnea (defined as modified Medical Research Council (mMRC) ≥ 2 with <1 point reduction or COPD Assessment Test (CAT) ≥ 10 with <4 point reduction after ≥3 months of LABA/LAMA therapy).
- Control group - Patients showing symptomatic improvement with the same therapy (mMRC <2 or ≥1 point reduction, or CAT <10 or ≥4 point reduction).
The primary analyses will explore clinical and physiological predictors of poor outcomes, using advanced statistical modeling such as linear mixed-effects models for longitudinal lung function trends, negative binomial regression for exacerbation risk, and Cox proportional hazards models for survival analysis.
Assessments:
Baseline and follow-up evaluations will include demographic and clinical data, comorbidities, smoking history, inhaler adherence and technique, spirometry, lung volume measurements, 6-minute walk tests, echocardiography, chest radiographs, and high-resolution CT scans. Blood tests will include complete blood count, inflammatory markers (C-reactive protein (CRP), fibrinogen), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac enzymes.
Statistical Analysis:
Longitudinal trends: Changes in lung function, symptoms, and exercise capacity will be assessed using linear mixed-effects models to evaluate the influence of clinical factors.
Acute exacerbations: The frequency of moderate-to-severe exacerbations will be analyzed using negative binomial regression or zero-inflated models when appropriate.
Mortality: Logistic regression will estimate 1-, 3-, and 5-year mortality risk, while Cox proportional hazards models will evaluate time-to-event outcomes.
Predictive modeling: Candidate biomarkers and imaging features will be incorporated into multivariable predictive models to identify key determinants of poor prognosis.
- Conditions
- COPD
- Keywords
- Chronic Obstructive Pulmonary Disease (COPD), Refractory Breathlessness, Persistent Dyspnea, Treatment Resistance, Unresponsive to Therapy
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Dyspnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| COPD patients with refractory breathlessness despite LABA/LAMA therapy | Patients with COPD who continue to experience clinically significant dyspnea (mMRC ≥ 2 or CAT ≥ 10) despite at least 3 months of treatment with dual long-acting bronchodilator therapy (LABA/LAMA), showing less than a 1-point reduction in mMRC or less than a 4-point reduction in CAT scores compared with baseline. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annual rate of acute exacerbations in COPD
Annualized rate of moderate-to-severe exacerbations per patient-year, defined as episodes requiring systemic corticosteroids, antibiotics, or hospitalization.
Moderate exacerbations will be defined as events requiring treatment with systemic corticosteroids and/or antibiotics without hospitalization. Severe exacerbations will be defined as events leading to hospitalization or emergency department visit.
Unit: Number of exacerbations per patient-year
Measured: Up to 5 years (annualized rate)
All-cause mortality
Proportion of participants who die from any cause Unit: Percentage of participants (%) or Number of deaths
Measured: 1-, 3-, and 5-year follow-up.
Secondary outcomes (2)
Annual forced expiratory volume in one second (FEV1) decline rate
Rate of change in forced expiratory volume in one second (FEV1) (Milliliters per year (mL/year)) measured by spirometry Annual decline in FEV1 will be assessed using linear mixed-effects models.
Measured: Baseline and annually for up to 5 years.
Annual forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC ratio) decline rate
Rate of change in post-bronchodilator forced expiratory volume in one second to forced vital capacity (FEV1/FVC ) ratio (%/year) measured by spirometry Annual decline in FEV1/FVC will be assessed using linear mixed-effects models.
Measured: Baseline and annually for up to 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2025
- Study start11 Apr 2024
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COPDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 730 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- Seoul National University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hyun Woo Lee, Seoul National University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07160322
- Sponsor's protocol ID
- 2024-0434
- Acronym
- RB-COPD
- Status last verified
- Jul 2025
- First submitted
- 20 Jul 2025
- Last updated
- 8 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared because the dataset contains sensitive personal health information, and there are no current plans or infrastructure for secure data sharing. Data will be used solely for analyses specified in the approved protocol and will remain confidential in accordance with institutional and IRB guidelines.
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prognosis and Clinical Outcomes of Refractory Dyspnea in Chronic Obstructive Pulmonary Disease: Prospective Observational Study
- ClinicalTrials.gov ID
- NCT07160322
- Acronym / sponsor ID
- RB-COPD / 2024-0434
- Conditions
- COPD
- Keywords
- Chronic Obstructive Pulmonary Disease (COPD), Refractory Breathlessness, Persistent Dyspnea, Treatment Resistance, Unresponsive to Therapy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 730 participants (estimated)
- Lead sponsor
- Seoul National UniversityUniversity, hospital or other
- Study start
- 11 Apr 2024 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 8 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to investigate the prognosis and clinical outcomes of patients with chronic obstructive pulmonary disease (COPD) who continue to experience refractory dyspnea despite treatment with long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA). The research will prospectively follow a cohort of patients to identify clinical factors, lung function parameters, imaging features, and cardiovascular indicators associated with poor treatment response. By comparing these patients with those who show symptom improvement, the study seeks to determine predictors of exacerbations, lung function decline, and mortality. Findings are expected to guide the development of targeted strategies to improve the management of refractory dyspnea in COPD.
Detailed description
The study aims to identify actionable clinical factors and develop predictive models that can enhance personalized management approaches for patients with refractory dyspnea in COPD.
This is a prospective observational cohort study designed to characterize patients with COPD who remain symptomatic despite standard inhaled therapy with LABA/LAMA combination. Participants will be enrolled from outpatient clinics and followed over time to assess changes in respiratory symptoms, lung function, exercise capacity, acute exacerbation frequency, and survival.
Key assessments include:
- Baseline demographic and clinical data (e.g., respiratory symptoms, comorbidities, smoking history).
- Pulmonary function tests (spirometry and lung volumes), exercise capacity evaluations, echocardiography, chest radiographs, and computed tomography (CT).
- Biomarker analysis (blood tests including inflammatory and cardiac markers).
Patients will be classified into two groups:
- Refractory COPD group - Patients with minimal improvement in dyspnea (defined as modified Medical Research Council (mMRC) ≥ 2 with <1 point reduction or COPD Assessment Test (CAT) ≥ 10 with <4 point reduction after ≥3 months of LABA/LAMA therapy).
- Control group - Patients showing symptomatic improvement with the same therapy (mMRC <2 or ≥1 point reduction, or CAT <10 or ≥4 point reduction).
The primary analyses will explore clinical and physiological predictors of poor outcomes, using advanced statistical modeling such as linear mixed-effects models for longitudinal lung function trends, negative binomial regression for exacerbation risk, and Cox proportional hazards models for survival analysis.
Assessments:
Baseline and follow-up evaluations will include demographic and clinical data, comorbidities, smoking history, inhaler adherence and technique, spirometry, lung volume measurements, 6-minute walk tests, echocardiography, chest radiographs, and high-resolution CT scans. Blood tests will include complete blood count, inflammatory markers (C-reactive protein (CRP), fibrinogen), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac enzymes.
Statistical Analysis:
Longitudinal trends: Changes in lung function, symptoms, and exercise capacity will be assessed using linear mixed-effects models to evaluate the influence of clinical factors.
Acute exacerbations: The frequency of moderate-to-severe exacerbations will be analyzed using negative binomial regression or zero-inflated models when appropriate.
Mortality: Logistic regression will estimate 1-, 3-, and 5-year mortality risk, while Cox proportional hazards models will evaluate time-to-event outcomes.
Predictive modeling: Candidate biomarkers and imaging features will be incorporated into multivariable predictive models to identify key determinants of poor prognosis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| COPD patients with refractory breathlessness despite LABA/LAMA therapy | – | –Patients with COPD who continue to experience clinically significant dyspnea (mMRC ≥ 2 or CAT ≥ 10) despite at least 3 months of treatment with dual long-acting bronchodilator therapy (LABA/LAMA), showing less than a 1-point reduction in mMRC or less than a 4-point reduction in CAT scores compared with baseline. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- This study will enroll adult patients (≥ 18 years) diagnosed with chronic obstructive pulmonary disease (COPD) according to the GOLD 2025 criteria, who are receiving combination therapy with long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA). Participants include both patients who continue to experience refractory dyspnea despite treatment and those who show symptomatic improvement. All participants must be able to attend regular outpatient visits and provide written informed consent.
Key inclusion criteria (7 listed)
- Adults (≥ 18 years) diagnosed with chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2025 criteria:
- Presence of COPD risk factors (e.g., smoking history, occupational exposure, genetic predisposition).
- Typical symptoms such as dyspnea, cough, or sputum production.
- Post-bronchodilator FEV1/FVC < 0.70.
- Regular outpatient follow-up at the respiratory clinic.
Key exclusion criteria (6 listed)
- Poor adherence to LABA/LAMA therapy (medication possession rate < 50%) or refusal of treatment.
- Inability or unwillingness to comply with scheduled visits, examinations, or follow-up procedures.
- Presence of severe comorbid conditions expected to significantly affect prognosis, including:
- Any condition that, in the opinion of the investigator, would interfere with study participation or data reliability.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Annual rate of acute exacerbations in COPD
Time frame: Up to 5 years (annualized rate)
Annualized rate of moderate-to-severe exacerbations per patient-year, defined as episodes requiring systemic corticosteroids, antibiotics, or hospitalization. Moderate exacerbations will be defined as events requiring treatment with systemic corticosteroids and/or antibiotics without hospitalization. Severe exacerbations will be defined as events leading to hospitalization or emergency department visit. Unit: Number of exacerbations per patient-year
All-cause mortality
Time frame: 1-, 3-, and 5-year follow-up.
Proportion of participants who die from any cause Unit: Percentage of participants (%) or Number of deaths
2 secondary outcomes
Annual forced expiratory volume in one second (FEV1) decline rate
Time frame: Baseline and annually for up to 5 years.
Annual forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC ratio) decline rate
Time frame: Baseline and annually for up to 5 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2025.
- Individual participant dataSharing planned: No. Individual participant data will not be shared because the dataset contains sensitive personal health information, and there are no current plans or infrastructure for secure data sharing. Data will be used solely for analyses specified in the approved protocol and will remain confidential in accordance with institutional and IRB guidelines.
Related trials for COPD
Not yet recruitingPhase 1/2
cfMSC Stem Cell Therapy Targeting COPD
Chronic Obstructive Pulmonary Disease (COPD)
Recruiting
Multimodal Assessment of NMES Effects on Respiratory and Peripheral Muscles in COPD
Chronic Obstructive Pulmonary Disease (COPD), Respiratory Muscle Dysfunction
RecruitingPhase 2/3
A Study to Investigate the Efficacy and Safety of Zelicapavir Compared With Placebo in Adults With RSV Who Are at High Risk for Severe Disease
RSV
Enrolling by invitationObservational study
Firefighter's Longitudinal Airway and Respiratory Exposome/Multiome Study (FLARES)
Anosmia, Chronic Obstructive Pulmonary Disease
RecruitingObservational study
Construction and Validation of an Impulse Oscillometry (IOS)-Based Platform for Screening, Diagnosis, and Management of Chronic Airway Diseases
Chronic Obstructive Pulmonary Disease (COPD), Asthma (Diagnosis)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COPD, run by Seoul National University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hyun Woo Lee, M.D. (82-10-9755-6172, athrunzara86@snu.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annual rate of acute exacerbations in COPD (time frame: Up to 5 years (annualized rate)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2025.