Study of Pulmonary Rehabilitation in Patients With Idiopathic Pulmonary Fibrosis (IPF)

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03717012
• Collaborator: (none)
• Enrollment: 19
• Locations: 19
• Arms: 2
• Actual Duration (Months): 18.8
• Patient Per Site: 1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main objectives of this study are:

• Determine the difference in change from baseline in Six Minute Walk Distance (6MWD) when pulmonary rehabilitation (PR) is added to stable underlying nintedanib therapy in patients with idiopathic pulmonary fibrosis (IPF)

• Determine the difference in change in Quality of Life (QoL) when pulmonary rehabilitation (PR) is added to stable underlying nintedanib therapy in patients with idiopathic pulmonary fibrosis (IPF)

• Determine if there is an enduring effect in 6MWD, QoL and lung function from pulmonary rehabilitation (PR) when pulmonary rehabilitation (PR) is added to stable underlying nintedanib therapy in patients with idiopathic pulmonary fibrosis (IPF)

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Nintedanib; Other: Pulmonary rehabilitation program	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Study of Pulmonary Rehabilitation In Nintedanib Treated Patients With IPF: Improvements in Activity, Exercise Endurance Time, and QoL
• Actual Study Start Date: Nov 15, 2018
• Actual Primary Completion Date: Mar 27, 2020
• Actual Study Completion Date: Jun 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nintedanib treatment alone	Drug: Nintedanib; stable dose
Experimental: Nintedanib with a pulmonary rehabilitation program	Drug: Nintedanib; stable dose; Other: Pulmonary rehabilitation program; 12 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the 6 Minute Walk Test (6MWD) at 12 Weeks [Baseline (day 1) and week 12 (day 85).]

   Absolute change from baseline in the 6 minute walk distance (6MWD) test at 12 weeks. The last assessment before treatment period start (included) will be used as baseline. If the baseline value is missing and the screening value is available, then the baseline value will be defined as the screening value taken closest to baseline date.

Secondary Outcome Measures

1. Change From Baseline in the 6 Minute Walk Test (6MWD) at 24 Weeks [Baseline (day 1) and week 24 (day 169).]

   Absolute change from baseline in the 6 minute walk distance (6MWD) test at 24 weeks. The last assessment before treatment period start (included) will be used as baseline. If the baseline value is missing and the screening value is available, then the baseline value will be defined as the screening value taken closest to baseline date.

2. Change From Baseline in the St George's Respiratory Questionnaire (SGRQ) Total Score at 12 and 24 Weeks [Baseline (day 1), week 12 (day 85) and week 24 (day 169).]

   Absolute change from baseline in the St George's Respiratory Questionnaire (SGRQ) total score at 12 and 24 weeks. The SGRQ is a widely used disease specific questionnaire evaluating health related quality of life. The SGRQ Total Score is measured using patient self-reported question on disease impact on symptoms, patient activity, and daily life. SGRQ scores are calculated using weights attached to each item of the questionnaire which provides an estimate of the distress associated with the symptoms or state described in each item. The total score for SGRQ ranges from 0 to 100, with higher scores indicating more limitations.

3. Absolute Change From Baseline in The King's Brief Interstitial Lung Disease (KBILD) Questionnaire Total Score at 12 and 24 Weeks [Baseline (day 1), week 12 (day 85) and week 24 (day 169).]

   Absolute change from baseline in The King's Brief Interstitial Lung Disease (KBILD) questionnaire total score at 12 and 24 weeks. The KBILD questionnaire is a disease specific questionnaire evaluating health related quality of life. The questionnaire consists of 15 items. Raw total scores were weighted with a Likert response scale to create the total score, total scores were transformed to a range of 0-100 ((actual score-lowest possible score/range)*100), with a score of 100 representing the best health status.

4. Change From Baseline in the University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOBQ) Total Score at 12 and 24 Weeks [Baseline (day 1), week 12 (day 85) and week 24 (day 169).]

   Change from baseline in the University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOBQ) total score at 12 and 24 weeks. The UCSD-SOBQ is a 24-item questionnaire that assesses self-reported shortness of breath while performing a variety of activities of daily living, scores for each item range from 0 to 5, with higher scores indicating more limitations. Total score is calculated as the sum of all individual scores. Scores range from 0 to 120, with higher scores indicating more limitations.

5. Absolute Change From Baseline of Forced Vital Capacity (FVC) at 12 and 24 Weeks [Baseline (day 1), week 12 (day 85) and week 24 (day 169).]

   Absolute change from baseline of forced vital capacity (FVC) at 12 and 24 weeks. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible.

6. Absolute Change From Baseline of Forced Vital Capacity (FVC) % Predicted at 12 and 24 Weeks [Baseline (day 1), week 12 (day 85) and week 24 (day 169).]

   Absolute change from baseline of forced vital capacity (FVC) % predicted at 12 and 24 weeks. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. For predicted normal values, different sites may use different prediction formulas, based on the method used to measure diffusing capacity of the lung for carbon monoxide (DLco). In any case, the method used must be in compliance with the European Respiratory Society (ERS)/American Thoracic Society (ATS) guideline on DLco measurements, and the prediction formula appropriate for that method.

7. Relative Change From Baseline of Forced Vital Capacity (FVC) at 12 and 24 Weeks [Baseline (day 1), week 12 (day 85) and week 24 (day 169).]

   Relative change (unitless) from baseline of forced vital capacity (FVC) at 12 and 24 weeks. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC is measured in milliliter (mL). Its relative change from baseline at 12 (24) weeks is calculated as: (FVC measured at 12 (24) weeks - FVC measured at baseline)/ FVC measured at baseline *100%.

8. Relative Change From Baseline of Forced Vital Capacity (FVC) % Predicted at 12 and 24 Weeks [Baseline (day 1), week 12 (day 85) and week 24 (day 169).]

   Relative change (unitless) from baseline of forced vital capacity (FVC) % predicted at 12 and 24 weeks. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. For predicted normal values, different sites may use different prediction formulas, based on the method used to measure diffusing capacity of the lung for carbon monoxide (DLco). In any case, the method used must be in compliance with the European Respiratory Society (ERS)/American Thoracic Society (ATS) guideline on DLco measurements, and the prediction formula appropriate for that method. The relative change from baseline of FVC % predicted at 12 (24) weeks is calculated as: (FVC % Predicted measured at 12 (24) weeks - FVC % Predicted measured at baseline)/ FVC % Predicted measured at baseline *100%.

9. Absolute Categorical Change of Forced Vital Capacity (FVC)% Predicted up to 12 and 24 Weeks (Decrease by >5%, Increase by >5%, and Change Within ≤5%) [Baseline (day 1), week 12 (day 85) and week 24 (day 169).]

   Absolute categorical change of forced vital capacity (FVC)% predicted up to 12 and 24 weeks, the following three categories were defined: decrease by >5%, increase by >5%, and change within ≤5%. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. For predicted normal values, different sites may use different prediction formulas, based on the method used to measure diffusing capacity of the lung for carbon monoxide (DLco). In any case, the method used must be in compliance with the European Respiratory Society (ERS)/American Thoracic Society(ATS) guideline on DLco measurements, and the prediction formula appropriate for that method.

10. Absolute Categorical Change of Forced Vital Capacity (FVC)% Predicted up to 12 and 24 Weeks (Decrease by >10%, Increase by >10%, and Change Within ≤10%) [Baseline (day 1), week 12 (day 85) and week 24 (day 169).]

    Absolute categorical change of forced vital capacity (FVC)% predicted up to 12 and 24 weeks, the following three categories were defined: decrease by >10%, increase by >10%, and change within ≤10%. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. For predicted normal values, different sites may use different prediction formulas, based on the method used to measure diffusing capacity of the lung for carbon monoxide (DLco). In any case, the method used must be in compliance with the European Respiratory Society (ERS)/American Thoracic Society(ATS) guideline on DLco measurements, and the prediction formula appropriate for that method.

11. Change From Baseline in Daily Accelerometer Activity From Baseline at 12 and 24 Weeks: Score of Average Steps/Day [Baseline (day 1), week 12 (day 85) and week 24 (day 169).]

    Change from baseline in daily accelerometer activity from baseline at 12 and 24 weeks: Score of average Steps/day. Categories were defined as follows: Steps (total daily value) 0 = 0 to 1900 steps/day = 1901 to 3700 steps/day = 3701 to 5500 steps/day = 5501 to 7300 steps/day = >7301 steps/day

12. Change From Baseline in Daily Accelerometer Activity From Baseline at 12 and 24 Weeks: Score of Average Vector Magnitude Units (VMU)/Day [Baseline (day 1), week 12 (day 85) and week 24 (day 169).]

    Change from baseline in daily accelerometer activity from baseline at 12 and 24 weeks: Score of average vector magnitude units (VMU)/day. Categories were defined as follows: VMU (daily VMU/min) 0 = 0 to 50 VMU/min = 51 to 110 VMU/min = 111 to 190 VMU/min = 191 to 270 VMU/min = 271 to 440 VMU/min = >441 VMU/min

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Patients being treated with a stable dose of nintedanib 150 mg BID for up to 30 months. Patients who have recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation.

• Age ≥ 40 years at screening

• Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient consent form

• Signed and dated written informed consent in accordance with ICH-GCP (International Council on Harmonization and Good Clinical Practice) and local legislation prior to admission to the trial

• Confirmed diagnosis of IPF according to 2011 American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guidelines by lung biopsy or High Resolution Computed Tomography (HRCT)(based upon INPULSIS criteria, (if biopsy only or HRCT done > 24 months prior to screening, a new HRCT to be done after consent and prior to or up to 7 days after Visit 2 for quantitative lung fibrosis score (QLF) for disease characterization)

• Forced Vital Capacity (FVC) ≥ 45% of predicted by the NHANES equation or equivalent (after discussion with Clinical Monitor), historical within past 30 days can be used. Carbon monoxide Diffusion Capacity (DLCO) (corrected for hemoglobin [Hgb]) 30-79% of predicted

• FEV1/FVC greater than/equal to .7

• Physically capable of performing both a 6 minute walk test and work rate cycle ergometry (sub-study patients), must successfully complete the practice tests for the 6 minute walk test, per the instructions. Potential sub-study patients that require supplemental oxygen or cannot complete the incremental work rate cycle ergometry test will not participate in the sub-study, but will qualify for the main study.

Exclusion criteria:

• Major surgery (major according to the investigator's assessment) performed within 12 weeks prior to randomization or planned within 6 months after screening, e.g. hip replacement which could interfere with the ability to participate in pulmonary rehabilitation.

• Any documented active or suspected malignancy or history of malignancy within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix

• Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial

• Previous enrolment in this trial (except for rescreening)

• Currently enrolled in another interventional investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatment(s)

• Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial

• Women who are pregnant, nursing, or who plan to become pregnant in the trial

• Previous participation in pulmonary rehabilitation program within 45 days prior to signing consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Loma Linda University Medical Center	Loma Linda	California	United States	92354
3	Western Connecticut Medical Group	Danbury	Connecticut	United States	06810
4	Miami VA Healthcare System	Miami	Florida	United States	33125
5	Coastal Pulmonary & Crit Care	Saint Petersburg	Florida	United States	33704
6	The LaPorte County Institute for Clinical Research	Michigan City	Indiana	United States	46360
7	Pulmonary and Critical Care Associates of Baltimore	Towson	Maryland	United States	21286
8	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
9	St. Vincent Physicians Sleep and Respiratory Center	Billings	Montana	United States	59101
10	Glacier View Research Institute	Kalispell	Montana	United States	59901
11	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
12	Pulmonix, LLC	Greensboro	North Carolina	United States	27403
13	Temple University Hospital	Oaks	Pennsylvania	United States	19456
14	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
15	Baylor University Medical Center	Dallas	Texas	United States	75246
16	Metroplex Pul and Sleep Ctr	McKinney	Texas	United States	75069-1769
17	University of Virginia Health System	Charlottesville	Virginia	United States	22903
18	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
19	Froedtert and The Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Dec 16, 2019
• Statistical Analysis Plan - Sep 18, 2020

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT03717012
• Other Study ID Numbers: 1199-0324
• First Posted: Oct 23, 2018
• Last Update Posted: Jun 9, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Nintedanib

Study Results

Participant Flow

Recruitment Details	This was a randomised, open-label, prospective, Phase IV clinical trial of pulmonary rehabilitation during the first 12 weeks of a 24-week treatment period, compared with no pulmonary rehabilitation, in patients already taking nintedanib for idiopathic pulmonary fibrosis.
Pre-assignment Detail	All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Period Title: Overall Study
STARTED	9	10
COMPLETED	8	4
NOT COMPLETED	1	6

Baseline Characteristics

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation	Total
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.	Total of all reporting groups
Overall Participants	9	10	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.0 (6.5)	70.9 (11.9)	69.1 (9.7)
Sex: Female, Male (Count of Participants)
Female	2 22.2%	2 20%	4 21.1%
Male	7 77.8%	8 80%	15 78.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 33.3%	1 10%	4 21.1%
Not Hispanic or Latino	6 66.7%	9 90%	15 78.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	9 100%	10 100%	19 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
6 minute walk distance (6MWD) test (meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meter]	360 (159.03)	322.33 (114.30)	340.17 (134.71)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the 6 Minute Walk Test (6MWD) at 12 Weeks
Description	Absolute change from baseline in the 6 minute walk distance (6MWD) test at 12 weeks. The last assessment before treatment period start (included) will be used as baseline. If the baseline value is missing and the screening value is available, then the baseline value will be defined as the screening value taken closest to baseline date.
Time Frame	Baseline (day 1) and week 12 (day 85).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 12 were excluded.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	7	8
Mean (Standard Deviation) [meter]	-20.60 (31.24)	-14.10 (53.99)

2. Secondary Outcome

Title	Change From Baseline in the 6 Minute Walk Test (6MWD) at 24 Weeks
Description	Absolute change from baseline in the 6 minute walk distance (6MWD) test at 24 weeks. The last assessment before treatment period start (included) will be used as baseline. If the baseline value is missing and the screening value is available, then the baseline value will be defined as the screening value taken closest to baseline date.
Time Frame	Baseline (day 1) and week 24 (day 169).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 24 were excluded.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	5	3
Mean (Standard Deviation) [meter]	-38.34 (63.24)	9.04 (10.82)

3. Secondary Outcome

Title	Change From Baseline in the St George's Respiratory Questionnaire (SGRQ) Total Score at 12 and 24 Weeks
Description	Absolute change from baseline in the St George's Respiratory Questionnaire (SGRQ) total score at 12 and 24 weeks. The SGRQ is a widely used disease specific questionnaire evaluating health related quality of life. The SGRQ Total Score is measured using patient self-reported question on disease impact on symptoms, patient activity, and daily life. SGRQ scores are calculated using weights attached to each item of the questionnaire which provides an estimate of the distress associated with the symptoms or state described in each item. The total score for SGRQ ranges from 0 to 100, with higher scores indicating more limitations.
Time Frame	Baseline (day 1), week 12 (day 85) and week 24 (day 169).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 12 or week 24 were excluded from their respective analyses.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	7	8
Change from baseline at week 12	5.60 (11.43)	-1.48 (9.03)
Change from baseline at week 24	6.06 (13.38)	-6.54 (4.97)

4. Secondary Outcome

Title	Absolute Change From Baseline in The King's Brief Interstitial Lung Disease (KBILD) Questionnaire Total Score at 12 and 24 Weeks
Description	Absolute change from baseline in The King's Brief Interstitial Lung Disease (KBILD) questionnaire total score at 12 and 24 weeks. The KBILD questionnaire is a disease specific questionnaire evaluating health related quality of life. The questionnaire consists of 15 items. Raw total scores were weighted with a Likert response scale to create the total score, total scores were transformed to a range of 0-100 ((actual score-lowest possible score/range)*100), with a score of 100 representing the best health status.
Time Frame	Baseline (day 1), week 12 (day 85) and week 24 (day 169).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 12 or week 24 were excluded from their respective analyses.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	7	8
Change from baseline at week 12	-3.20 (3.21)	1.28 (5.36)
Change from baseline at week 24	-4.42 (8.80)	-0.63 (4.87)

5. Secondary Outcome

Title	Change From Baseline in the University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOBQ) Total Score at 12 and 24 Weeks
Description	Change from baseline in the University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOBQ) total score at 12 and 24 weeks. The UCSD-SOBQ is a 24-item questionnaire that assesses self-reported shortness of breath while performing a variety of activities of daily living, scores for each item range from 0 to 5, with higher scores indicating more limitations. Total score is calculated as the sum of all individual scores. Scores range from 0 to 120, with higher scores indicating more limitations.
Time Frame	Baseline (day 1), week 12 (day 85) and week 24 (day 169).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 12 or week 24 were excluded from their respective analyses.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	7	8
Change from baseline at week 12	13.29 (12.63)	6.13 (18.71)
Change from baseline at week 24	17.50 (14.54)	0.00 (19.97)

6. Secondary Outcome

Title	Absolute Change From Baseline of Forced Vital Capacity (FVC) at 12 and 24 Weeks
Description	Absolute change from baseline of forced vital capacity (FVC) at 12 and 24 weeks. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible.
Time Frame	Baseline (day 1), week 12 (day 85) and week 24 (day 169).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 12 or week 24 were excluded from their respective analyses.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	7	8
Change from baseline at week 12	-152.86 (261.90)	-87.50 (277.32)
Change from baseline at week 24	76.00 (356.13)	-86.67 (168.62)

7. Secondary Outcome

Title	Absolute Change From Baseline of Forced Vital Capacity (FVC) % Predicted at 12 and 24 Weeks
Description	Absolute change from baseline of forced vital capacity (FVC) % predicted at 12 and 24 weeks. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. For predicted normal values, different sites may use different prediction formulas, based on the method used to measure diffusing capacity of the lung for carbon monoxide (DLco). In any case, the method used must be in compliance with the European Respiratory Society (ERS)/American Thoracic Society (ATS) guideline on DLco measurements, and the prediction formula appropriate for that method.
Time Frame	Baseline (day 1), week 12 (day 85) and week 24 (day 169).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 12 or week 24 were excluded from their respective analyses.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	7	8
Change from baseline at week 12	-3.84 (7.93)	-1.50 (7.42)
Change from baseline at week 24	3.63 (11.69)	-1.93 (4.44)

8. Secondary Outcome

Title	Relative Change From Baseline of Forced Vital Capacity (FVC) at 12 and 24 Weeks
Description	Relative change (unitless) from baseline of forced vital capacity (FVC) at 12 and 24 weeks. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC is measured in milliliter (mL). Its relative change from baseline at 12 (24) weeks is calculated as: (FVC measured at 12 (24) weeks - FVC measured at baseline)/ FVC measured at baseline *100%.
Time Frame	Baseline (day 1), week 12 (day 85) and week 24 (day 169).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 12 or week 24 were excluded from their respective analyses.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	7	8
Change from baseline at week 12	-3.68 (9.35)	-2.60 (9.02)
Change from baseline at week 24	2.80 (10.12)	-2.16 (4.64)

9. Secondary Outcome

Title	Relative Change From Baseline of Forced Vital Capacity (FVC) % Predicted at 12 and 24 Weeks
Description	Relative change (unitless) from baseline of forced vital capacity (FVC) % predicted at 12 and 24 weeks. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. For predicted normal values, different sites may use different prediction formulas, based on the method used to measure diffusing capacity of the lung for carbon monoxide (DLco). In any case, the method used must be in compliance with the European Respiratory Society (ERS)/American Thoracic Society (ATS) guideline on DLco measurements, and the prediction formula appropriate for that method. The relative change from baseline of FVC % predicted at 12 (24) weeks is calculated as: (FVC % Predicted measured at 12 (24) weeks - FVC % Predicted measured at baseline)/ FVC % Predicted measured at baseline *100%.
Time Frame	Baseline (day 1), week 12 (day 85) and week 24 (day 169).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 12 or week 24 were excluded from their respective analyses.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	7	8
Change from baseline at week 12	-3.68 (9.35)	-2.60 (9.02)
Change from baseline at week 24	2.80 (10.12)	-2.16 (4.64)

10. Secondary Outcome

Title	Absolute Categorical Change of Forced Vital Capacity (FVC)% Predicted up to 12 and 24 Weeks (Decrease by >5%, Increase by >5%, and Change Within ≤5%)
Description	Absolute categorical change of forced vital capacity (FVC)% predicted up to 12 and 24 weeks, the following three categories were defined: decrease by >5%, increase by >5%, and change within ≤5%. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. For predicted normal values, different sites may use different prediction formulas, based on the method used to measure diffusing capacity of the lung for carbon monoxide (DLco). In any case, the method used must be in compliance with the European Respiratory Society (ERS)/American Thoracic Society(ATS) guideline on DLco measurements, and the prediction formula appropriate for that method.
Time Frame	Baseline (day 1), week 12 (day 85) and week 24 (day 169).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 12 or week 24 were excluded from their respective analyses.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	7	8
Decrease by >5%	4 44.4%	2 20%
Within 5% change	2 22.2%	5 50%
Increase by >5%	1 11.1%	1 10%
Decrease by >5%	1 11.1%	1 10%
Within 5% change	2 22.2%	2 20%
Increase by >5%	2 22.2%	0 0%

11. Secondary Outcome

Title	Absolute Categorical Change of Forced Vital Capacity (FVC)% Predicted up to 12 and 24 Weeks (Decrease by >10%, Increase by >10%, and Change Within ≤10%)
Description	Absolute categorical change of forced vital capacity (FVC)% predicted up to 12 and 24 weeks, the following three categories were defined: decrease by >10%, increase by >10%, and change within ≤10%. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. For predicted normal values, different sites may use different prediction formulas, based on the method used to measure diffusing capacity of the lung for carbon monoxide (DLco). In any case, the method used must be in compliance with the European Respiratory Society (ERS)/American Thoracic Society(ATS) guideline on DLco measurements, and the prediction formula appropriate for that method.
Time Frame	Baseline (day 1), week 12 (day 85) and week 24 (day 169).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 12 or week 24 were excluded from their respective analyses.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	7	8
Decrease by >10%	2 22.2%	1 10%
Within 10% change	5 55.6%	7 70%
Increase by >10%	0 0%	0 0%
Decrease by >10%	0 0%	0 0%
Within 10% change	4 44.4%	3 30%
Increase by >10%	1 11.1%	0 0%

12. Secondary Outcome

Title	Change From Baseline in Daily Accelerometer Activity From Baseline at 12 and 24 Weeks: Score of Average Steps/Day
Description	Change from baseline in daily accelerometer activity from baseline at 12 and 24 weeks: Score of average Steps/day. Categories were defined as follows: Steps (total daily value) 0 = 0 to 1900 steps/day = 1901 to 3700 steps/day = 3701 to 5500 steps/day = 5501 to 7300 steps/day = >7301 steps/day
Time Frame	Baseline (day 1), week 12 (day 85) and week 24 (day 169).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 12 or week 24 were excluded from their respective analyses.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	5	6
Change from baseline at week 12	0.4 (0.9)	0.5 (0.5)
Change from baseline at week 24	-0.8 (1.7)	0.0 (0.0)

13. Secondary Outcome

Title	Change From Baseline in Daily Accelerometer Activity From Baseline at 12 and 24 Weeks: Score of Average Vector Magnitude Units (VMU)/Day
Description	Change from baseline in daily accelerometer activity from baseline at 12 and 24 weeks: Score of average vector magnitude units (VMU)/day. Categories were defined as follows: VMU (daily VMU/min) 0 = 0 to 50 VMU/min = 51 to 110 VMU/min = 111 to 190 VMU/min = 191 to 270 VMU/min = 271 to 440 VMU/min = >441 VMU/min
Time Frame	Baseline (day 1), week 12 (day 85) and week 24 (day 169).

Outcome Measure Data

Analysis Population Description

Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not. Patients with no data available at week 12 or week 24 were excluded from their respective analyses.

Arm/Group Title	Nintedanib 150 mg	Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
Measure Participants	5	6
Change from baseline at week 12	0.4 (0.9)	0.3 (0.8)
Change from baseline at week 24	-0.5 (1.7)	-0.5 (0.7)

Adverse Events

Time Frame	From first Nintedanib drug intake on/after randomization (or re-start of nintedanib if interruption) to the last Nintedanib drug intake plus 28 days plus one day. Up to 263 days.
Adverse Event Reporting Description	Randomized set (RS): This patient set includes all randomized patients, whether treated with pulmonary rehabilitation or not.
Arm/Group Title	Nintedanib 150 mg		Nintedanib 150 mg + Pulmonary Rehabilitation
Arm/Group Description	Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial.		Subjects were required to be treated on a stable (up to 30 months) dose of nintedanib 150 milligram (mg) twice a day (BID) administered per prescribing instructions and to continue on this dose throughout the trial. Patients who recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Patients that have had an interruption in nintedanib treatment or a temporary dose reduction can be entered into the trial when they have returned to a dose of 150 mg BID and their condition is determined to be stable by the investigator and temporary dose reductions to treat adverse events is permitted during the trial. In addition patients received a standard pulmonary rehabilitation regimen two or three times weekly for 12 weeks. The pulmonary rehabilitation should follow the facility's standard regimen as long as the regimen meets basic standards.
All Cause Mortality
	Nintedanib 150 mg		Nintedanib 150 mg + Pulmonary Rehabilitation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		1/10 (10%)
Serious Adverse Events
	Nintedanib 150 mg		Nintedanib 150 mg + Pulmonary Rehabilitation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/9 (33.3%)		2/10 (20%)
Hepatobiliary disorders
Cholecystitis acute	1/9 (11.1%)		0/10 (0%)
Infections and infestations
Influenza	1/9 (11.1%)		0/10 (0%)
Injury, poisoning and procedural complications
Fall	0/9 (0%)		1/10 (10%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung cancer metastatic	0/9 (0%)		1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Idiopathic pulmonary fibrosis	1/9 (11.1%)		1/10 (10%)
Other (Not Including Serious) Adverse Events
	Nintedanib 150 mg		Nintedanib 150 mg + Pulmonary Rehabilitation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/9 (44.4%)		6/10 (60%)
Gastrointestinal disorders
Abdominal pain	0/9 (0%)		1/10 (10%)
Abdominal pain lower	1/9 (11.1%)		0/10 (0%)
Colitis microscopic	0/9 (0%)		1/10 (10%)
Constipation	0/9 (0%)		1/10 (10%)
Diarrhoea	1/9 (11.1%)		1/10 (10%)
Haemorrhoids	0/9 (0%)		1/10 (10%)
Nausea	0/9 (0%)		1/10 (10%)
Rectal haemorrhage	0/9 (0%)		1/10 (10%)
Infections and infestations
Mycoplasma infection	0/9 (0%)		1/10 (10%)
Nasopharyngitis	1/9 (11.1%)		0/10 (0%)
Sinusitis	2/9 (22.2%)		0/10 (0%)
Upper respiratory tract infection	2/9 (22.2%)		0/10 (0%)
Investigations
Alanine aminotransferase increased	1/9 (11.1%)		0/10 (0%)
Aspartate aminotransferase increased	1/9 (11.1%)		0/10 (0%)
Blood glucose increased	0/9 (0%)		1/10 (10%)
Gamma-glutamyltransferase increased	1/9 (11.1%)		0/10 (0%)
Lymphocyte percentage decreased	0/9 (0%)		1/10 (10%)
Mean platelet volume decreased	0/9 (0%)		1/10 (10%)
Neutrophil percentage increased	0/9 (0%)		1/10 (10%)
Metabolism and nutrition disorders
Abnormal loss of weight	0/9 (0%)		1/10 (10%)
Musculoskeletal and connective tissue disorders
Back pain	1/9 (11.1%)		0/10 (0%)
Intervertebral disc compression	0/9 (0%)		1/10 (10%)
Rotator cuff syndrome	0/9 (0%)		1/10 (10%)
Synovial cyst	1/9 (11.1%)		0/10 (0%)
Psychiatric disorders
Agitation	0/9 (0%)		1/10 (10%)
Confusional state	0/9 (0%)		1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Cough	1/9 (11.1%)		0/10 (0%)
Oropharyngeal pain	1/9 (11.1%)		0/10 (0%)
Sinus congestion	0/9 (0%)		1/10 (10%)
Skin and subcutaneous tissue disorders
Skin irritation	0/9 (0%)		1/10 (10%)

Limitations/Caveats

Trial was terminated prematurely due to difficulties with recruitment and a global BI recruitment hold implemented on 17 March 2020 because of the COVID-19 pandemic. The recruitment rate was slow and the target number of participants to be recruited was not reached. No inferential statistical analysis was performed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.