UMIN-CTR Clinical Trial

Public title

Effects of Long-acting muscarinic antagonist(LAMA) and Long-acting beta-two-agonist (LABA) combination on dynamic pulmonary hyperinflation

Acronym

Effect of bronchodilator combination on dynamic pulmonary hyperinflation

Scientific Title

Effects of Long-acting muscarinic antagonist(LAMA) and Long-acting beta-two-agonist (LABA) combination on dynamic pulmonary hyperinflation

Scientific Title:Acronym

Effect of bronchodilator combination on dynamic pulmonary hyperinflation

Region

Japan

Condition

Chronic Obstructive Pulmonary Disease

Classification by specialty

Pneumology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

the purpose in this study was performed to elucidate the effects of combined treatment with tiotropium and olodaterol on DLH following hyperventilation.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Explanatory

Developmental phase

Phase IV

Primary outcomes

The primary outcome was defined as decrease in inspiratory capacity (IC) from rest by metronome-paced incremental hyperventilation(MPIH), which is an index of dynamic lung hyperinflation(DLH). after 8 weeks with treatment.

Key secondary outcomes

The secondary outcomes were COPD assessment test (CAT), FEV1, and 6-minute walking distance (6MWD). In addition to, as in previous studies, we investigated whether there are correlations between changes by treatment in DLH and exercise tolerance or dyspnea on exercise after 8weeks with treatment.

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

Treatment

Type of intervention

Medicine

Interventions/Control_1

Treatment was on the day after completion of the baseline examination, and consisted of administration of tiotropium/olodaterol 5/5 micro grum inhalation solution (2.5/2.5 microgram per actuation) by soft-mist inhaler. Patients were instructed to inhale two puffs from the inhaler, once a day, in the morning.

The combination of LAMA and LABA used consisted of Spiolt and Respimat, respectively (Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan), which contained 2.5 microgram of tiotropium and 2.5 microgram of olodaterol per puff, respectively.

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

35

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

All patients suffered from smoking-related COPD without alpha 1 antitrypsin deficiency, and those with a smoking history of 10 pack-year or more including current smoker were selected for this study. In addition, as a substitute for LAMA and LABA during the washout period, patients who responded to symptoms with short-acting treatment were selected as eligible for inclusion. After receiving a thorough explanation of the study, patients who provided written consent were enrolled in the study

Key exclusion criteria

Patients with dysuria due to prostate hypertrophy, glaucoma, severe heart failure, exacerbation and/or respiratory infection within 3 months, prior history of lung surgery, severe heart disease, or impairment or difficulty in walking due to motor or cognitive dysfunction were excluded. Exacerbation history criteria was defined as an acute worsening of respiratory symptoms that result in additional therapy.

Target sample size

38

Name of lead principal investigator

1st name
Middle name
Last name	Shohei Kawachi

Organization

Shinshu University Hospital

Division name

Department of Rehabilitation

Zip code

Address

3-1-1, Asahi, Matsumoto, 390-8621, Japan

TEL

0263-37-2836

Email

drodman@shinshu-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Shohei Kawachi

Organization

Shinshu University Hospital

Division name

Department of Rehabilitation

Zip code

Address

3-1-1, Asahi, Matsumoto, 390-8621, Japan

TEL

0263-37-2836

Homepage URL

Email

drodman@shinshu-u.ac.jp

Institute

Shinshu University Hospital,Department of Rehabilitation

Institute

Department

Personal name

Organization

The authors receive financial support by Nihon rehabilitation Shinkokai Foundation, a general incoroprated foundation (Koganei, Tokyo, Japan)

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

信州大学医学部附属病院(長野県)、 新生病院（長野県）

Date of disclosure of the study information

2017

Year

05

Month

31

Day

URL releasing protocol

Publication of results

Partially published

URL related to results and publications

Number of participants that the trial has enrolled

Results

Five of the 38 registered patients dropped out of the study. The reasons for dropping out were hospitalization due to gastrointestinal disorder, discontinuation of hospital visits for unknown reasons, refusal to undergo examination after treatment, hospitalization due to exacerbation of respiratory diseases, and did not meet the criteria of COPD after registration into the study in one patient each. All results were not trough values. Because.

Characteristics of patients and comparison of lung functions before and after treatment
The study population included patients with mild to severe disease as determined by classification of airflow limitation severity using %FEV1, 60% of all subjects were moderate disease status. FEV1, %FEV1, and FEV1/FVC (forced vital capacity) ratio were significantly higher after in comparison to before treatment , while CAT was lower after treatment.
Comparison of dynamic lung hyperinflation following metronome-paced incremental hyperventilation (MPIH) and 6MWT before and after treatment
-IC20, -IC30, and -IC40 were significantly decreased after treatment. IC20, IC30, and IC40 increased significantly after treatment. In addition, deltaIC was significantly decreased after treatment. The 6MWD was significantly increased after treatment.

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

Completed

Date of protocol fixation

2017

Year

03

Month

06

Day

Date of IRB

Anticipated trial start date

2017

Year

04

Month

11

Day

Last follow-up date

2018

Year

11

Month

30

Day

Date of closure to data entry

2018

Year

11

Month

30

Day

Date trial data considered complete

2019

Year

03

Month

09

Day

Date analysis concluded

Other related information

Correlation of changes in DLH, FEV1, exercise tolerance, and dyspnea with treatment
There were not significant correlations between changes in each IC, FEV1, 6MWD, and BSmax with treatment.

Registered date

2017

Year

05

Month

29

Day

Last modified on

2019

Year

03

Month

09

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031493