Trial Outcomes & Findings for INREAL - Nintedanib for Changes in Dyspnea and Cough in Patients Suffering From Chronic Fibrosing Interstitial Lung Disease (ILD) With a Progressive Phenotype in Everyday Clinical Practice: a Real-world Evaluation (NCT NCT04702893)

Last Updated: 2025-04-25

Results Overview

The correlation between the change from baseline to week 52 (week 52 - baseline) in forced vital capacity (FVC) \[% predicted\] and change from baseline to week 52 (week 52 - baseline) in dyspnea symptom score was calculated using the Pearson's coefficient of correlation. The forced vital capacity measures the amount of air that can be forcefully exhaled from the lungs after a maximum inhalation. The dyspnea symptom score was measured using the living with pulmonary fibrosis questionnaire (L-PF). The L-PF contained a dyspnea symptom module with 12 items to assess the severity of shortness of breath, where the higher the score, the greater the impairment. The coefficient of correlation ranges from -1 to 1, indicating a negative association between the variables the closer it is to -1 and a positive association the closer it is to 1.

Recruitment status

COMPLETED

Target enrollment

108 participants

Primary outcome timeframe

At baseline and at week 52±6.

Results posted on

2025-04-25

Participant Flow

Single-arm, open-label observational cohort study investigating the effect of nintedanib on patient-reported outcomes (PROs) like dyspnea and cough in chronic interstitial lung disease (ILD) patients (excluding idiopathic pulmonary fibrosis (IPF)) over 52 weeks.

Only patients that met all inclusion and none of the exclusion criteria were included.

Participant milestones

Participant milestones
Measure	Nintedanib-treated Patients Patients diagnosed with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (excluding idiopathic pulmonary fibrosis (IPF)), who did not receive previous antifibrotic treatment, received 150 milligrams (mg) of nintedanib twice daily, administered 12 hours apart, according to the approved label, for approximately 52 weeks. Participants who did not tolerate 150 mg of nintedanib switched to 100 mg twice daily.
Overall Study STARTED	108
Overall Study Treated	102
Overall Study COMPLETED	71
Overall Study NOT COMPLETED	37

Reasons for withdrawal

Reasons for withdrawal
Measure	Nintedanib-treated Patients Patients diagnosed with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (excluding idiopathic pulmonary fibrosis (IPF)), who did not receive previous antifibrotic treatment, received 150 milligrams (mg) of nintedanib twice daily, administered 12 hours apart, according to the approved label, for approximately 52 weeks. Participants who did not tolerate 150 mg of nintedanib switched to 100 mg twice daily.
Overall Study Other reasons than listed	11
Overall Study Withdrawal by Subject	3
Overall Study Lost to Follow-up	7
Overall Study Death	10
Overall Study Not treated	6

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nintedanib-treated Patients n=102 Participants Patients diagnosed with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (excluding idiopathic pulmonary fibrosis (IPF)), who did not receive previous antifibrotic treatment, received 150 milligrams (mg) of nintedanib twice daily, administered 12 hours apart, according to the approved label, for approximately 52 weeks. Participants who did not tolerate 150 mg of nintedanib switched to 100 mg twice daily.
Age, Continuous	70.47 Years STANDARD_DEVIATION 10.74 • n=102 Participants
Sex: Female, Male Female	38 Participants n=102 Participants
Sex: Female, Male Male	64 Participants n=102 Participants
Forced vital capacity (FVC) [% predicted]	65.18 Percentage STANDARD_DEVIATION 18.86 • n=98 Participants • Only TS patients without missing baseline data were included.
Living with pulmonary fibrosis questionnaire (L-PF) dyspnea symptom score	24.71 Units on a scale STANDARD_DEVIATION 18.56 • n=101 Participants • Only TS patients without missing baseline data were included.
Living with pulmonary fibrosis questionnaire (L-PF) cough symptom score	37.46 Units on a scale STANDARD_DEVIATION 25.67 • n=101 Participants • Only TS patients without missing baseline data were included.

PRIMARY outcome

Timeframe: At baseline and at week 52±6.

Population: Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib. Patients with missing data were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Nintedanib-treated Patients n=38 Participants Patients diagnosed with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (excluding idiopathic pulmonary fibrosis (IPF)), who did not receive previous antifibrotic treatment, received 150 milligrams (mg) of nintedanib twice daily, administered 12 hours apart, according to the approved label, for approximately 52 weeks. Participants who did not tolerate 150 mg of nintedanib switched to 100 mg twice daily.
Correlation Between Change From Baseline to Week 52 in Forced Vital Capacity (FVC) [% Predicted] and Change From Baseline to Week 52 in Dyspnea Symptom Score	-0.2576 Pearson's coefficient of correlation Interval -0.5333 to 0.0677

PRIMARY outcome

Timeframe: At baseline and at week 52±6.

Population: Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib. Patients with missing data were excluded from the analysis.

The correlation between the change from baseline to week 52 (week 52 - baseline) in forced vital capacity (FVC) \[% predicted\] and change from baseline to week 52 (week 52 - baseline) in cough symptom score was calculated using the Pearson's coefficient of correlation. The forced vital capacity measures the amount of air that can be forcefully exhaled from the lungs after a maximum inhalation. The cough symptom score was measured using the living with pulmonary fibrosis questionnaire (L-PF). The L-PF contained a cough symptom module with 6 items to assess the severity of cough symptoms, where the higher the score, the more severe the cough. The coefficient of correlation ranges from -1 to 1, indicating a negative association between the variables the closer it is to -1 and a positive association the closer it is to 1.

Outcome measures

Outcome measures
Measure	Nintedanib-treated Patients n=38 Participants Patients diagnosed with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (excluding idiopathic pulmonary fibrosis (IPF)), who did not receive previous antifibrotic treatment, received 150 milligrams (mg) of nintedanib twice daily, administered 12 hours apart, according to the approved label, for approximately 52 weeks. Participants who did not tolerate 150 mg of nintedanib switched to 100 mg twice daily.
Correlation Between Change From Baseline to Week 52 in Forced Vital Capacity (FVC) [% Predicted] and Change From Baseline to Week 52 in Cough Symptom Score	-0.1093 Pearson's coefficient of correlation Interval -0.4145 to 0.218

SECONDARY outcome

Timeframe: At baseline and at week 52±6.

Population: Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib. Patients with missing data were excluded from the analysis.

The correlation between the change from baseline to week 52 (week 52 - baseline) in forced vital capacity (FVC) \[mL\] and change from baseline to week 52 (week 52 - baseline) in dyspnea symptom score was calculated using the Pearson's coefficient of correlation. The forced vital capacity measures the amount of air that can be forcefully exhaled from the lungs after a maximum inhalation. The dyspnea symptom score was measured using the living with pulmonary fibrosis questionnaire (L-PF). The L-PF contained a dyspnea symptom module with 12 items to assess the severity of shortness of breath, where the higher the score, the greater the impairment. The coefficient of correlation ranges from -1 to 1, indicating a negative association between the variables the closer it is to -1 and a positive association the closer it is to 1.

Outcome measures

Outcome measures
Measure	Nintedanib-treated Patients n=38 Participants Patients diagnosed with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (excluding idiopathic pulmonary fibrosis (IPF)), who did not receive previous antifibrotic treatment, received 150 milligrams (mg) of nintedanib twice daily, administered 12 hours apart, according to the approved label, for approximately 52 weeks. Participants who did not tolerate 150 mg of nintedanib switched to 100 mg twice daily.
Correlation Between Change From Baseline to Week 52 in Forced Vital Capacity (FVC) [mL] and Change From Baseline to Week 52 in Dyspnea Symptom Score	-0.2909 Pearson's coefficient of correlation Interval -0.5587 to 0.0317

SECONDARY outcome

Timeframe: At baseline and at week 52±6.

Population: Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib. Patients with missing data were excluded from the analysis.

The correlation between the change from baseline to week 52 (week 52 - baseline) in forced vital capacity (FVC) \[mL\] and change from baseline to week 52 (week 52 - baseline) in cough symptom score was calculated using the Pearson's coefficient of correlation. The forced vital capacity measures the amount of air that can be forcefully exhaled from the lungs after a maximum inhalation. The cough symptom score was measured using the living with pulmonary fibrosis questionnaire (L-PF). The L-PF contained a cough symptom module with 6 items to assess the severity of cough symptoms, where the higher the score, the more severe the cough. The coefficient of correlation ranges from -1 to 1, indicating a negative association between the variables the closer it is to -1 and a positive association the closer it is to 1.

Outcome measures

Outcome measures
Measure	Nintedanib-treated Patients n=38 Participants Patients diagnosed with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (excluding idiopathic pulmonary fibrosis (IPF)), who did not receive previous antifibrotic treatment, received 150 milligrams (mg) of nintedanib twice daily, administered 12 hours apart, according to the approved label, for approximately 52 weeks. Participants who did not tolerate 150 mg of nintedanib switched to 100 mg twice daily.
Correlation Between Change From Baseline to Week 52 in Forced Vital Capacity (FVC) [mL] and Change From Baseline to Week 52 in Cough Symptom Score	-0.1566 Pearson's coefficient of correlation Interval -0.4536 to 0.1717

SECONDARY outcome

Timeframe: MMRM included measurements at week 13±6, week 26±6, week 39±6 and week 52±6. Change from baseline values at week 52±6 is reported.

Population: Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib. Only patients with at least one post baseline value and baseline value were included in the analysis.

This outcome measured the absolute change from baseline to week 52 in the cough symptom score, assessed by the living with pulmonary fibrosis questionnaire (L-PF). The L-PF includes a cough symptom module with 6 items to evaluate the severity of cough symptoms. Each item is scored on a scale of 0 to 4, with higher scores indicating more severe symptoms. The total cough symptom score was calculated using the formula: (sum of each individual score/24)\*100, ranging from 0 to 100, where the higher the score, the more severe the cough. Results were calculated as \[Week 52\] - \[Baseline\]. The analysis was performed using a mixed model for repeated measures (MMRM) with fixed independent effects for baseline value, visit, and baseline-by-visit interaction, and a random effect for each patient. Within-patient errors were represented using an unstructured variance-covariance structure.

Outcome measures

Outcome measures
Measure	Nintedanib-treated Patients n=91 Participants Patients diagnosed with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (excluding idiopathic pulmonary fibrosis (IPF)), who did not receive previous antifibrotic treatment, received 150 milligrams (mg) of nintedanib twice daily, administered 12 hours apart, according to the approved label, for approximately 52 weeks. Participants who did not tolerate 150 mg of nintedanib switched to 100 mg twice daily.
Absolute Change From Baseline in Living With Pulmonary Fibrosis Questionnaire (L-PF) Cough Symptom Score [Points] at Week 52	3.86 Units on a scale Standard Error 3.28

SECONDARY outcome

Timeframe: MMRM included measurements at week 13±6, week 26±6, week 39±6 and week 52±6. Change from baseline values at week 52±6 is reported.

This outcome measured the absolute change from baseline to week 52 in the dyspnea symptom score, assessed by the living with pulmonary fibrosis questionnaire (L-PF). The L-PF includes a dyspnea symptom module with 12 items to evaluate the severity of dyspnea symptoms. Each item is scored on a scale of 0 to 5, with higher scores indicating more severe symptoms. The total dyspnea symptom score was calculated using the formula: (sum of each individual score/total score possible)\*100, ranging from 0 to 100, where the higher the score, the more severe the dyspnea. Results were calculated as \[Week 52\] - \[Baseline\]. The analysis was performed using a mixed model for repeated measures (MMRM) with fixed independent effects for baseline value, visit, and baseline-by-visit interaction, and a random effect for each patient. Within-patient errors were represented using an unstructured variance-covariance structure.

Outcome measures

Outcome measures
Measure	Nintedanib-treated Patients n=91 Participants Patients diagnosed with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (excluding idiopathic pulmonary fibrosis (IPF)), who did not receive previous antifibrotic treatment, received 150 milligrams (mg) of nintedanib twice daily, administered 12 hours apart, according to the approved label, for approximately 52 weeks. Participants who did not tolerate 150 mg of nintedanib switched to 100 mg twice daily.
Absolute Change From Baseline in Living With Pulmonary Fibrosis Questionnaire (L-PF) Dyspnea Symptom Score [Points] at Week 52	6.26 Units on a scale Standard Error 2.35

Adverse Events

Nintedanib-treated Patients

Serious events: 16 serious events

Other events: 45 other events

Deaths: 10 deaths

Serious adverse events

Serious adverse events
Measure	Nintedanib-treated Patients n=102 participants at risk Patients diagnosed with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (excluding idiopathic pulmonary fibrosis (IPF)), who did not receive previous antifibrotic treatment, received 150 milligrams (mg) of nintedanib twice daily, administered 12 hours apart, according to the approved label, for approximately 52 weeks. Participants who did not tolerate 150 mg of nintedanib switched to 100 mg twice daily.
Cardiac disorders Myocardial infarction	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
General disorders Death	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
General disorders Disease progression	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
General disorders General physical health deterioration	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
General disorders Sudden death	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Hepatobiliary disorders Hepatic cirrhosis	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Immune system disorders Hypersensitivity	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Infections and infestations Nasal abscess	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Infections and infestations Pneumonia	2.0% 2/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Infections and infestations Urinary tract infection	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Investigations Inflammatory marker increased	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Metabolism and nutrition disorders Hypocalcaemia	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin squamous cell carcinoma metastatic	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Renal and urinary disorders Prerenal failure	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.9% 3/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.98% 1/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.

Other adverse events

Other adverse events
Measure	Nintedanib-treated Patients n=102 participants at risk Patients diagnosed with chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (excluding idiopathic pulmonary fibrosis (IPF)), who did not receive previous antifibrotic treatment, received 150 milligrams (mg) of nintedanib twice daily, administered 12 hours apart, according to the approved label, for approximately 52 weeks. Participants who did not tolerate 150 mg of nintedanib switched to 100 mg twice daily.
Gastrointestinal disorders Diarrhoea	41.2% 42/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.
Gastrointestinal disorders Nausea	7.8% 8/102 • Adverse events and all-cause mortality: From first nintedanib administration to 52±6 weeks thereafter plus 28 days of residual effect period. Up to 62 weeks. Treated set (TS): All patients with signed informed consent who received at least one dose of nintedanib.

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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
Publication restrictions are in place

Restriction type: OTHER