UMIN-CTR Clinical Trial

Public title

An Exploratory Clinical Study on the Impact of Pulmonary Circulation on Patients with COPD

Acronym

An Exploratory Clinical Study on the Impact of Pulmonary Circulation on Patients with COPD

Scientific Title

An Exploratory Clinical Study on the Impact of Pulmonary Circulation on Patients with COPD

Scientific Title:Acronym

An Exploratory Clinical Study on the Impact of Pulmonary Circulation on Patients with COPD

Region

Japan

Condition

Chronic Obstructive Pulmonary Disease (COPD)

Classification by specialty

Medicine in general	Cardiology	Pneumology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To comprehensively evaluate pulmonary circulatory parameters, including pulmonary vascular resistance (PVR), in patients with COPD, and to clarify how pulmonary circulatory abnormalities affect COPD pathophysiology and prognosis.

Basic objectives2

Others

Basic objectives -Others

To investigate whether echocardiographic parameters, including right ventricular isovolumic relaxation time (IRT), can serve as non-invasive indices of pulmonary vascular resistance.
To analyze associations between pulmonary circulatory parameters (PVR, IRT, TAPSE/PASP, %CSA, etc.) and pulmonary function, exercise capacity, physical activity, and circulating biomarkers.
To explore whether pulmonary circulatory parameters predict clinical outcomes such as acute exacerbations, hospitalization, and home-stay survival.

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Primary outcomes

To examine the relationship between pulmonary circulation parameters, including pulmonary vascular resistance (PVR) and the prognosis in patients with COPD.

Key secondary outcomes

Associations between pulmonary circulatory parameters (PVR, IRT, TAPSE/PASP, %CSA, etc.) and pulmonary function indices (FEV1% predicted, DLCO% predicted, VC% predicted).
Associations between pulmonary circulatory parameters and exercise capacity (6-minute walk distance [6MWD], treadmill exercise test metrics) and daily physical activity.
Associations between pulmonary circulatory parameters and circulating biomarkers such as NT-proBNP.
Prognostic value of pulmonary circulatory parameters for acute exacerbations, respiratory-related hospitalization, all-cause hospitalization, home-stay survival, and overall survival.
Improvement in risk stratification when adding IRT to existing clinical prediction models (e.g., age, sex, FEV1%, DLCO%, TRV).

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

NO

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Prevention

Type of intervention

Maneuver

Interventions/Control_1

Right Heart Catheter

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

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patients with COPD who were enrolled under UMIN ID: UMIN000042159 and completed a two-year observation period. Patients aged 20 years or older, of either sex. Patients diagnosed with COPD at this hospital (WHO functional class II, III, or IV) who do not exhibit hypoxemia at rest or during the 6-minute walk test (6MWT). Patients with decreased activities of daily living (ADL) or dyspnea related to hypoxemia are excluded in order to minimize the influence of hypoxic pulmonary vasoconstriction (HPV) as a potential cause of pulmonary hypertension (PH) associated with reduced arterial oxygen pressure (PaO2 < 60 mmHg). Patients with hypoxemia (PaO2 < 60 mmHg) who are receiving long-term oxygen therapy (LTOT) and whose hypoxemia is adequately corrected are included. Patients with respiratory symptoms that remained stable for at least three months prior to enrollment, requiring no change in treatment, yet persistent and gradually progressive despite COPD therapy, who underwent right heart catheterization. Patients with exercise-induced elevated pulmonary artery pressure (eePAP) or mild PH requiring therapeutic intervention, characterized by pulmonary artery wedge pressure (PAWP) <= 15 mmHg and mean pulmonary artery pressure (mPAP) < 25 mmHg at rest, with exercise mPAP (mPAPOE) >= 30 mmHg or resting mPAP >= 25 mmHg but < 35 mmHg. Both inpatients and outpatients were eligible. All patients provided written informed consent before participation in the study.

Key exclusion criteria

Patients who have received or will receive bosentan or other PAH-specific medications (e.g., phosphodiesterase type 5 (PDE-5) inhibitors, endothelin receptor antagonists, or prostaglandin analogs)
Patients with diseases that may cause right heart overload (During the registration process for this study, patients identified through echocardiography, electrocardiogram, oxygen saturation monitoring, imaging studies, etc., with diseases that may cause right heart overload, such as obstructive sleep apnea and cardiovascular comorbidities like HFpEF, were excluded.)
Patients with PAWP exceeding 15 mmHg
Patients with hypoxia (PaO2 < 60 mmHg) during the 6MWT [Patients in whom hypoxia (PaO2 < 60 mmHg) was corrected with long-term oxygen therapy (LTOT) (i.e., patients who received LTOT to ensure PaO2 > 60 mmHg at rest and during the 6MWT and were deemed equivalent to COPD patients receiving routine therapy in clinical practice, allowing monitoring of changes in their condition, prognosis, and ADL functional capacity) were excluded.]
Patients with a history of asthma, a bronchodilator response (BDR) to 400 mcg of salbutamol with an FEV1 change of and or more than 200 mL, peripheral eosinophilia (>150 cells/mcL), typical asthma symptoms of atopy, or a history of IgE > 170 IU/ml
Women who are pregnant, may be pregnant, or are lactating
Other patients deemed ineligible for this study by the principal investigator (e.g., those with diseases or conditions other than COPD that might affect ADL, such as arrhythmias, left ventricular failure, pulmonary thromboembolism, connective tissue diseases, intervertebral disc herniation, as confirmed through history-taking, physical examination, chest X-ray, echocardiography, lung perfusion scintigraphy, and various parameter measurements conducted during the run-in period).

Target sample size

35

Name of lead principal investigator

1st name	Yosuke
Middle name
Last name	Tanaka

Organization

Nippon Medical School

Division name

Department of Respiratory Medicine

Zip code

113-8603

Address

1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan

TEL

0338222131

Email

yosuke-t@nms.ac.jp

Name of contact person

1st name	Yosuke
Middle name
Last name	Tanaka

Organization

Nippon Medical School

Division name

Department of Respiratory Medicine

Zip code

113-8603

Address

1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan

TEL

0338222131

Homepage URL

Email

yosuke-t@nms.ac.jp

Institute

Nippon Medical School

Institute

Department

Personal name

Yosuke Tanaka

Organization

Nippon Medical School

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

the medical ethics committee of Nippon Medical School

Address

1-1-5, Sendagi, Bunkyo-ku, Tokyo

Tel

0338222131

Email

yosuke-t@nms.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

日本医科大学付属病院

Date of disclosure of the study information

2024

Year

09

Month

23

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

Open public recruiting

Date of protocol fixation

2020

Year

09

Month

01

Day

Date of IRB

2020

Year

09

Month

01

Day

Anticipated trial start date

2020

Year

09

Month

01

Day

Last follow-up date

2027

Year

10

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2024

Year

09

Month

23

Day

Last modified on

2025

Year

10

Month

05

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000063532

Single case data URL

Value
https://center6.umin.ac.jp/ice/63532