UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Efficacy of long-acting bronchodilators on dynamic lung hyperinflation in chronic obstructive pulmonary disease.
Title of the study (Brief title)	Bronchodilator on dynamic hyperinflation
Region	Japan

Condition
Condition	Chronic obstructive pulmonary disease (COPD)
Classification by specialty	Pneumology Adult
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	Dynamic lung hyperinflation (DLH) is an important phenomenon that causes dyspnea and restricts exercise capacity in chronic obstructive pulmonary disease (COPD). It has been shown that improvements in dyspnea on effort following bronchodilator therapy correlate well with reductions in lung hyperinflation, as indicated by increases in inspiratory capacity (IC). There are two bronchodilators with different action mechanisms, long-acting muscarinic antagonist (LAMA) and long-acting beta (2)-agonist (LABA). However, little evidence of a difference between LAMA and LABA and an additive effect of LABA with LAMA regarding DLH has been demonstrated. DLH has been generally evaluated based on the size of the reduction in IC measured during or immediately after exercise loading. We have reported a method of quantitatively determining dynamic hyperinflation following hyperventilation in which respiratory rate is incrementally increased without exercise loading (metronome-paced incremental hyperventilation, MPIH) and the resulting change in IC is measured. The purpose is to determine the superiority of the efficacies among the monotherapies of LAMA, tiotropium (Respimat inhaler), and LABA, indacaterol, and the combination therapy of LAMA and LABA for the DLH evaluated by the method of MPIH.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Not applicable

Assessment
Primary outcomes	Dynamic lung hyperinflation
Key secondary outcomes	FEV1, lung volumes, airway resistance, respiratory impedance, walking distance evaluated by shuttle walking test, health status evaluated by a questionnaire of the COPD assessment test (CAT), activity of daily life (ADL) evaluated using the questionnaire of the pulmonary emphysema activity of daily life score (P-ADL).

Base
Study type	Interventional

Study design
Basic design	Cross-over
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	The study design is a random open-label crossover study. The subjects are divided into two groups at random for an accurate evaluation of the influence of the order of drug treatments with tiotropium and indacaterol. One group is treated with a 5 microgram once-daily dosage of tiotropium through a soft mist inhaler (Respimat inhaler) for 4 weeks following a 4 week-treatment with a 150 microgram once-daily dosage of indacaterol through a dry powder inhaler, finally, is treated with the combination of the two drugs (tiotropium + indacaterol) for 4 weeks.
Interventions/Control_2	The other group is treated with indacaterol for 4 weeks following a 4-week treatment with tiotropium in the same manner; finally, the other group is treated with the combination of the two drugs (tiotropium + indacaterol) for 4 weeks.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	45 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	We recruite symptomatic patients with stable COPD from the outpatient clinic of Shinshu University Hospital. COPD is diagnosed based on clinical history and symptoms and by the pulmonary function characterized by irreversible airflow limitation in accordance with the GOLD guidelines. All subjects had smoking-related COPD without alfa1-antitrypsin deficiency and had a smoking history of more than 30 pack-years.
Key exclusion criteria	The patients who have any history of asthma or asthmatic symptoms, walking disability, severe arrhythmia, or heart failure, those who have suffered from respiratory tract infection or exacerbation of COPD during the preceding three months, and those who have been treated with oral steroids and/or long-term oxygen therapy were excluded from the study.
Target sample size	30

Research contact person
Name of lead principal investigator	Keisaku Fujimoto
Organization	Shinshu University School of Health Sciences
Division name	Department of Clinical Laboratory Sciences
Address	3-1-1, Asahi, Matsumoto, Naganoken, 390-8621, Japan
TEL	0263-37-2393
Email	keisaku@shinshu-u.ac.jp

Public contact
Name of contact person	Keisaku Fujimoto
Organization	Shinshu University School of Health Sciences
Division name	Department of Clinical Laboratory Sciences
Address	3-1-1, Asahi, Matsumoto, Naganoken, 390-8621, Japan
TEL	0263-37-2393
Homepage URL
Email	keisaku@shinshu-u.ac.jp

Sponsor
Institute	Shinshu University School of Health Sciences
Institute
Department

Funding Source
Organization	Shinshu University School of Health Sciences
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2017 Year 05 Month 24 Day

Progress
Recruitment status	Main results already published
Date of protocol fixation	2012 Year 09 Month 03 Day
Anticipated trial start date	2012 Year 11 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Partially published
URL releasing results
Results
Other related information

Management information
Registered date	2017 Year 05 Month 22 Day
Last modified on	2017 Year 05 Month 22 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031429