UMIN-CTR Clinical Trial

Public title

Japanese Multicenter Study for Identifying Unmet Needs in COPD Patients

Acronym

J-UNMET-COPD

Scientific Title

Japanese Multicenter Study for Identifying Unmet Needs in COPD Patients

Scientific Title:Acronym

J-UNMET-COPD

Region

Japan

Condition

chronic obstructive pulmonary disease (COPD)

Classification by specialty

Pneumology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Patients with chronic obstructive pulmonary disease (COPD) who have been receiving guideline-based optimal inhaled therapy for more than 6 months will be prospectively observed for 3 years, with exacerbation frequency as the primary endpoint and the following as secondary endpoints: severity of exacerbations that occur, changes in post-bronchodilator forced expiratory volume in one second (FEV1), changes in symptom questionnaire scores, occurrence and nature of cardiovascular events, COPD medication changes, changes in imaging findings, progression to frailty and pre-frailty, and disease stability. Through comparison between patients with and without exacerbations over the 3-year period, we will elucidate the demographic characteristics (age, sex, body mass index [BMI], smoking history), clinical characteristics (COPD severity, comorbidities, IgE, peripheral blood eosinophil count, fractional exhaled nitric oxide [FeNO], pulmonary function tests, COPD Assessment Test [CAT] score, modified Medical Research Council Dyspnea Scale [mMRC], number of exacerbations [in the year prior to enrollment], etc.), and molecular pathological features (transcriptomic and proteomic analyses of sputum and peripheral blood mononuclear cells) at enrollment in patients who experience exacerbations. This study aims to identify unmet medical needs in COPD patients continuing optimal inhaled therapy and to clarify their clinical and molecular pathological characteristics.

Basic objectives2

Others

Basic objectives -Others

The basic objective of this study is to prospectively observe patients with chronic obstructive pulmonary disease (COPD) who have been receiving guideline-based optimal inhaled therapy for more than 6 months over a 3-year period to evaluate exacerbation frequency and identify differences in clinical and molecular pathological characteristics between patients who experience exacerbations and those who do not.

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Not applicable

Primary outcomes

The primary endpoint is the frequency of moderate to severe exacerbations (annual exacerbation rate) over a 3-year period in patients with COPD who have been receiving optimal inhaled therapy (ICS/LAMA/LABA triple therapy or LAMA/LABA dual therapy) for 6 months or more.

Rationale for Primary Endpoint Selection:

- Clinical Significance: COPD exacerbations represent the most critical outcome with substantial impact on patient prognosis, quality of life, and healthcare economics. Moderate to severe exacerbations (requiring systemic corticosteroids or antibiotics, or hospitalization) are well-established to be strongly associated with irreversible decline in lung function, increased cardiovascular event risk, and elevated mortality.

- Scientific Validity: Exacerbation frequency has been adopted as a standard primary endpoint in large-scale clinical trials (IMPACT, ETHOS, KRONOS trials, etc.) and represents the international gold standard for treatment efficacy assessment.

- Measurability: Exacerbation definition and severity grading are clearly established (administration of systemic corticosteroids or antibiotics, hospitalization) and can be objectively evaluated.

- Assessment Timeline:

Baseline evaluation: At enrollment

Regular assessments: Evaluation of exacerbations occurring in the previous 12 months at 1-year, 2-year, and 3-year timepoints (recording date of occurrence, severity, treatment details, and outcomes)

- Analysis Timeline: Calculated as annual exacerbation rate following completion of the 3-year observation period

Key secondary outcomes

(1) Exacerbation-Related Endpoints

Exacerbation severity distribution: Proportions of mild, moderate, and severe exacerbations

Assessment timing: At time of exacerbation occurrence and during annual evaluations

Time to first exacerbation: Number of days from enrollment to first moderate or severe exacerbation

Exacerbation-related hospitalization rate: Annual hospitalization rate and length of hospital stay

Recovery period after exacerbation: Number of days from exacerbation onset to symptom stabilization

(2) Pulmonary Function Endpoints

Change in post-bronchodilator FEV1: Absolute change from baseline (mL) and percentage change (%)

Assessment timing: At enrollment, 1 year, 2 years, and 3 years

Annual FEV1 decline rate: Calculated from longitudinal FEV1 changes over 3 years (mL/year)

Change in FVC: Change from baseline

(3) Patient-Reported Outcomes (PRO)

Change in CAT (COPD Assessment Test) score

Assessment timing: At enrollment, 1 year, 2 years, and 3 years

Minimal clinically important difference (MCID): Change of > or = 2 points

Change in mMRC (modified Medical Research Council) dyspnea scale

Assessment timing: Same as above

MCID: Change of > or =1 grade

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

40

years-old

<=

Age-upper limit

85

years-old

>

Gender

Male and Female

Key inclusion criteria

(1) Disease: Chronic obstructive pulmonary disease (COPD) and non-COPD patients. COPD diagnosis follows the current Guidelines for the Diagnosis and Treatment of COPD 2022 (Japanese Respiratory Society). COPD diagnostic criteria require post-bronchodilator spirometry showing FEV1/FVC < 0.70, presence of exposure factors such as long-term smoking history, and exclusion of other diseases that may cause airflow obstruction.

(2) Disease stage, severity, and diagnostic criteria
COPD patients meeting all of the following conditions:
Post-bronchodilator spirometry showing FEV1/FVC < 0.70

(3) Age: 40 years or older and 85 years or younger (at enrollment)

(4) Sex: Both male and female patients are eligible for both COPD and non-COPD groups

(5) Smoking history: Regarding smoking as a major risk factor for COPD, 10 pack-years (daily cigarettes/20 x years of smoking) or more is the standard criterion in clinical research, therefore smoking history is defined as having 10 pack-years or more of smoking. Those with smoking history are either currently smoking (current smokers) or have a history of past smoking (former smokers). COPD patients with smoking history are eligible.

(6) Treatment history: Stable patients who have been continuing triple therapy (ICS/LAMA/LABA), LABA/LAMA dual therapy, or monotherapy such as LABA alone or LAMA alone for at least 6 months. At least 6 months of continuation from treatment initiation is required to adequately evaluate the effects of optimal inhaled therapy.

(7) Definition of exacerbation
Exacerbation is defined as worsening of respiratory symptoms (dyspnea, cough, sputum) requiring additional treatment beyond usual maintenance therapy.


(8) Definition of stable state
Patients with no occurrence of COPD exacerbation within 4 weeks prior to study enrollment

(9) Individuals from whom written informed consent for study participation has been obtained

Key exclusion criteria

(1) Asthma: Cases with asthma as the primary diagnosis are excluded (however, asthma-COPD overlap is not an exclusion criterion and will be included as a subgroup for analysis)

(2) Individuals with other clinically significant pulmonary diseases (diffuse lung disease [however, combined pulmonary fibrosis and emphysema may be included if obstructive ventilatory impairment is present], active respiratory infections, etc.)

(3) Individuals who experienced COPD exacerbation within 4 weeks prior to study enrollment and received treatment with systemic corticosteroids and/or antibiotics

(4) Individuals who suffered from active infections or cardiovascular disease events within 4 weeks prior to study enrollment

(5) Individuals with dementia or psychiatric disorders that prevent completion of self-administered questionnaires

(6) Individuals who are pregnant or possibly pregnant, breastfeeding, or planning pregnancy during the study participation period

Target sample size

500

Name of lead principal investigator

1st name	Naoya
Middle name
Last name	Fujino

Organization

Tohoku University Hospital

Division name

Department of Respiratory Medicine

Zip code

980-8574

Address

1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi

TEL

022-717-8539

Email

naoya.fujino.d2@tohoku.ac.jp

Name of contact person

1st name	Naoya
Middle name
Last name	Fujino

Organization

Tohoku University Hospital

Division name

Department of Respiratory Medicine

Zip code

980-8574

Address

1-1 Seiryocho, Aobaku, Sendai, Miyagi

TEL

022-717-8539

Homepage URL

Email

naoya.fujino.d2@tohoku.ac.jp

Institute

Tohoku University

Institute

Department

Personal name

Organization

JSPS

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Ethics Committee Tohoku University Graduate School of Medicine

Address

2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan

Tel

022-728-4105

Email

ec-med@grp.tohoku.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2026

Year

03

Month

01

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2025

Year

12

Month

20

Day

Date of IRB

Anticipated trial start date

2026

Year

01

Month

01

Day

Last follow-up date

2030

Year

11

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This prospective observational study aims to identify unmet medical needs in patients with chronic obstructive pulmonary disease (COPD) who have been receiving guideline-based optimal inhaled therapy for at least 6 months. The study will enroll 500 participants aged 40-85 years: 400 COPD patients (300 receiving triple therapy and 100 receiving monotherapy) and 100 non-COPD patients, followed for 3 years. The primary endpoint is exacerbation frequency, while secondary endpoints include exacerbation severity, changes in pulmonary function, symptom questionnaire scores, cardiovascular events, medication changes, imaging findings, frailty progression, and disease stability. By comparing patients with and without exacerbations, the study will analyze demographic, clinical, and molecular pathological characteristics through omics analysis of sputum and peripheral blood mononuclear cells. This comprehensive approach will elucidate the unmet medical needs of COPD patients receiving optimal treatment and identify the underlying pathophysiological mechanisms.

Registered date

2025

Year

10

Month

15

Day

Last modified on

2025

Year

10

Month

15

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000067915