Muco-active Agent Use and Clinical Outcomes After Lung Cancer Diagnosis in Chronic Obstructive Pulmonary Disease

NCT07712016 | Active Not Recruiting

• 1 other identifier: 07-2026-06
• Study Type: observational
• Target: 27,000
• Locations: 1 country
• Sites: 2

Brief Summary

The Target Trial Emulation of Muco-active Agent Use and Clinical Outcomes After Lung Cancer Diagnosis Among Patients With Chronic Obstructive Pulmonary Disease (TAME-CLC) study is a retrospective observational cohort study using existing real-world data from the Korean Cancer Data Center (K-CURE) database to evaluate whether use of muco-active agents is associated with clinical outcomes after lung cancer diagnosis among adults with chronic obstructive pulmonary disease (COPD) and localized-stage lung cancer. The investigators will not assign any treatment or medication. Instead, the study will emulate a hypothetical target trial using routinely collected retrospective data. Eligible patients will be adults aged 40 to less than 80 years who have COPD before lung cancer diagnosis and meet prespecified diagnostic and treatment-based criteria. Patients will be classified according to muco-active agent treatment strategies based on prescription records after the first lung cancer diagnosis. The emulated treatment strategy is use of any muco-active agent within a prespecified grace period after lung cancer diagnosis. The comparator strategy is no muco-active agent use during the same grace period. Muco-active agents include mucolytics, mucoregulators, expectorants, and mucokinetics, such as N-acetylcysteine, erdosteine, carbocysteine, guaifenesin, ivy-leaf extract, ambroxol, and bromhexine. The primary outcome is time to moderate-to-severe COPD exacerbation after lung cancer diagnosis. Secondary outcomes include all-cause mortality, cancer-related mortality, and respiratory disease-related mortality. A clone-censoring-weighting approach will be used within a target trial emulation framework to estimate the modified intention-to-treat effect of muco-active agent use while adjusting for measured baseline differences between treatment strategies.

Conditions

Lung Cancer (Diagnosis); Chronic Obstructive Pulmonary Disease (COPD)

Keywords

Pulmonary Disease, Chronic Obstructive; Lung Neoplasms; Expectorants; Disease Exacerbation; Neoplasm Staging

Outcome Measures

Primary Outcomes (1)

• Time to moderate-to-severe COPD exacerbation

  Moderate-to-severe chronic obstructive pulmonary disease (COPD) exacerbation will be defined as the first occurrence of either moderate or severe exacerbation. Moderate exacerbation is defined as an outpatient COPD exacerbation requiring systemic corticosteroids and/or antibiotics. Severe exacerbation is defined as hospitalization or an emergency department visit due to a COPD exacerbation.

  From treatment strategy assignment until the first occurrence of moderate-to-severe COPD exacerbation, death, loss of eligibility, or 60 months after lung cancer diagnosis.

Secondary Outcomes (1)

• Time to all-cause mortality

  60 months after treatment assignment

Study Arms (2)

Muco-active agent

Eligible patients initiating any muco-active agent within 4 weeks after the first diagnosis of localized-stage lung cancer. Alternative 2-, 6-, and 8-week grace periods will be evaluated in sensitivity analyses. Muco-active agents include mucolytics, mucoregulators, mucokinetics, and expectorants, including N-acetylcysteine, erdosteine, carbocysteine, ambroxol, bromhexine, guaifenesin, and ivy-leaf extract. Exposure strategies will be emulated using prescription records from the Korean Cancer Data Center (K-CURE) database.

Drug: Muco-active agents

No muco-active agent use

Eligible patients who do not receive any muco-active agent within the 4-week grace period following the first diagnosis of localized-stage lung cancer.

Other: No muco-active agent use

Interventions

No muco-active agent use OTHER

Comparator exposure strategy defined as no prescription, medication order, or dispensing record for a prespecified muco-active agent during the exposure assessment window after the index date.

No muco-active agent use

Muco-active agents DRUG

Exposure is defined as initiation of any prespecified muco-active agent during the 4-week grace period, with alternative 2-, 6-, and 8-week grace periods evaluated in sensitivity analyses, after the first diagnosis of localized-stage lung cancer. Drug exposure will be identified using prescription records from the Korean Cancer Data Center (K-CURE) database. Patients receiving muco-active agents during the 12-week washout period before lung cancer diagnosis will be excluded to emulate a new-user target trial. Exposure classification follows the predefined treatment strategies specified in the target trial protocol.

Also known as: Mucolytics, Expectorants, N-acetylcysteine, Carbocysteine, Carbocisteine, Erdosteine, Ambroxol

Muco-active agent

Eligibility Criteria

• Age: 40 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will include adults aged 40 to 79 years with chronic obstructive pulmonary disease (COPD) diagnosed before newly diagnosed localized-stage lung cancer in the Korean Cancer Data Center (K-CURE) database from January 1, 2002, to December 31, 2023. Eligibility will be determined using prespecified diagnostic, treatment, prescription, procedure, washout, and follow-up criteria. Patients who used muco-active agents during the 12-week washout period before lung cancer diagnosis will be excluded to support a new-user design. Treatment strategies and outcomes will be identified using prescription, clinical, and mortality records.

You may qualify if:

• Adults aged 40 to 79 years.
• Diagnosis of chronic obstructive pulmonary disease before lung cancer diagnosis.
• Newly diagnosed localized-stage lung cancer.
• Stable COPD and lung cancer treatment regimen at baseline.
• Eligible for one of the predefined treatment strategies.
• Available baseline information and follow-up data.

You may not qualify if:

• Asthma or bronchiectasis.
• Long-term oxygen therapy.
• Severe medical comorbidities defined in the protocol.
• Neurologic diseases affecting prognosis.
• Muco-active agent use during the 12-week washout period.
• Missing essential baseline variables.

Sponsors & Collaborators

• Seoul National University: lead
• National Cancer Center, Korea: collaborator

Study Sites (2)

National Cancer Center,

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Seoul National University College of Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center

Seoul, Select..., 07061, South Korea

Location

MeSH Terms

Conditions

Lung Neoplasms; Disease; Pulmonary Disease, Chronic Obstructive; Disease Progression

Interventions

Expectorants; Acetylcysteine; Carbocysteine; erdosteine; Ambroxol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Respiratory System Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Bromhexine; Aniline Compounds; Amines; Cyclohexylamines

Study Officials

• Hyun Woo Lee, MD, PhD

  Department of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine

  PRINCIPAL INVESTIGATOR

• Jiyu Sun

  Integrated Biostatistics Branch, Division of Cancer Data Science, National Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: July 17, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (2)