UMIN-CTR Clinical Trial

Basic information
Public title	Long-term Effect of Pulmonary Rehabilitation under Nintedanib treatment in Idiopathic Pulmonary Fibrosis
Acronym	Long-term Effect of Pulmonary Rehabilitation under Nintedanib treatment in IPF
Scientific Title	Long-term Effect of Pulmonary Rehabilitation under Nintedanib treatment in Idiopathic Pulmonary Fibrosis
Scientific Title:Acronym	Long-term Effect of Pulmonary Rehabilitation under Nintedanib treatment in IPF
Region	Japan

Condition
Condition	Idiopathic pulmonary fibrosis(IPF)
Classification by specialty	Pneumology Rehabilitation medicine
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To assess the efficacy and safety of long-term pulmonary rehabilitation (PR) in patients with IPF under nintedanib therapy. For long-term PR, sustainable long-term maintenance rehabilitation is followed to a short-term induction pulmonary rehabilitation program.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase IV

Assessment
Primary outcomes	Change from baseline in 6 minute walk distance (6MWD) (m) after 12 months of treatment
Key secondary outcomes	Main secondary endpoints: Change from baseline in endurance time in cycle ergometer after 12 months of treatment Other secondary endpoints: Following endpoints will be assessed after 12 months. 1)Change from baseline in SGRQ total score 2)Relative change from baseline (%) in 6MWD 3)Physical activity (triaxial accelerometer), health status (SGRQ domain scores and CAT score), dyspnoea (TDI, dyspnoea-12), HADS 4)FVC, DLCO, PaO2, SpO2 (at rest and after 6MWD test) 5)Rate of mortality and rate of unscheduled hospitalization 6)In addition to the assessment of 12 months, change from baseline in 6 minute walk distance (m) and all secondary endpoints will be assessed after 6 months of treatment. 7)Compliance to planed long term rehabilitation (ratio: actual/plan) in nintedanib + rehabilitation group 8)Percentage of patients whose compliance are >= 70% (good compliant patients) in the nintedanib + rehabilitation group 9)Change from baseline (m) in 6 minute walk distance in good compliant patients

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	NO
Dynamic allocation	YES
Institution consideration	Institution is considered as adjustment factor in dynamic allocation.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Educational,Counseling,Training
Type of intervention	Medicine Device,equipment Other
Interventions/Control_1	Short-term induction pulmonary rehabilitation (2/1w for the first 12w) + Maintenance pulmonary rehabilitation and outpatient visit (1/4w) Total 52w. / No intervention
Interventions/Control_2	Nintedanib / both group
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	40 years-old <=
Age-upper limit	80 years-old >
Gender	Male and Female
Key inclusion criteria	1)Patients aged 40 =< and < 80 years at informed consent 2)Patient with IPF diagnosed according to the diagnosis criteria of INPULSIS trial and 2011 IPF guideline 3)200m=<6MWD of the past=<600m 4)Patient with dyspnoea on exercise (1=<mMRC=<3) 5)Stable patients without any infection nor acute exacerbation within 3 months 6)Patients who are already receiving Nintedanib at least 4 weeks prior to participating the study and expected to be able to take nintedanib for more than 12 months in this study 7)Patients who can visit hospital for the first twice a week, and every 2-4 weeks for follow 40 weeks to take outpatient rehabilitation program. 8)Patients who can comply with the instructed exercise and record it in diary. 9)Patients who can adequately answer to the PRO(QOL) questionnaire 10)%FVC>=50%, 79%>=%DLco>=30% 11)Written informed consent is obtained
Key exclusion criteria	1)Patients with connective tissue disease, known neuromuscular disease or other orthopedic problem which may affect to exercise assessment, other disease requires exercise limitation 2)Patients who received pulmonary rehabilitation within 12 months 3)Patients with oral corticosteroids >15mg/day (prednisolone equivalent) or immunosuppressive agents within 3 months 4)Patients with pirfenidone within 3 months 5)Patients with unstable angina, a history of myocardial infarction or received percutaneous transluminal coronary angioplasty or coronary-artery bypass surgery within 1 month or a history of a cerebrovascular disease within 6 months. 6)Patients who requires antiarrhythmic therapy 7)Patients with serious pulmonary hypertension 8)ALT or AST > 2x upper limit of normal 9)Total bilirubin > 2x upper limit of normal 10)Creatinine clearance < 30mL/min 11)Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin) or high dose antiplatelet therapy. 12)Pregnant women and women of possibly pregnant. 13)Patients who cannot be evaluated by 6 minute walk test for any reason. 14)Other patients who are judged by the investigator as not adequate to participate in the study. 15)History of malignant disease within 3 years.
Target sample size	84

Research contact person
Name of lead principal investigator	1st name Ryo Middle name Last name Kozu
Organization	Nagasaki University
Division name	Institute of Biomedical Sciences
Zip code	8528523
Address	1-7-1 Sakamoto, Nagasaki, Japan
TEL	+95-819-7963
Email	ryokozu@nagasaki-u.ac.jp

Public contact
Name of contact person	1st name Kensuke Middle name Last name Kataoka
Organization	Tosei General Hospital
Division name	Respiratory Medicine and Allergy
Zip code	489-8642
Address	160 Nishi-oiwake-cho, Seto city, Aichi, Japan
TEL	+561-82-5101
Homepage URL
Email	kataoka@tosei.or.jp

Sponsor
Institute	Central Japan Lung Study Grou
Institute
Department

Funding Source
Organization	Nipponn Boehringer Ingelheim CO ., Ltd.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization	Tosei General Hospital IRB
Address	160 Nishi-oiwake-cho, Seto city, Aichi, Japan
Tel	+561-82-5101
Email	ychikenn@tosei.or.jp

Secondary IDs
Secondary IDs	YES
Study ID_1	No.605
Org. issuing International ID_1	Tosei General Hospital IRB
Study ID_2	17082106
Org. issuing International ID_2	Nagasaki University Hospital
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2017 Year 03 Month 03 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
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

Progress
Recruitment status	Completed
Date of protocol fixation	2017 Year 01 Month 11 Day
Date of IRB	2017 Year 08 Month 22 Day
Anticipated trial start date	2017 Year 09 Month 01 Day
Last follow-up date	2020 Year 12 Month 31 Day
Date of closure to data entry	2021 Year 01 Month 31 Day
Date trial data considered complete	2021 Year 05 Month 14 Day
Date analysis concluded	2021 Year 06 Month 24 Day

Other
Other related information

Management information
Registered date	2017 Year 03 Month 03 Day
Last modified on	2021 Year 07 Month 30 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030312