Lung Diseases, Interstitial
Conditions
Brief summary
The primary objective of this observational study is to investigate the correlation between changes from baseline at 52 weeks in forced vital capacity (FVC) and changes from baseline at 52 weeks in dyspnea score points or cough score points as measured with the pulmonary fibrosis questionnaire (L-PF) questionnaire over 52 weeks of nintedanib treatment in patients suffering from chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (excluding idiopathic pulmonary fibrosis (IPF)).
Interventions
DRUGNintedanib
150 or 100 milligrams (mg) of nintedanib, when 150 mg is not tolerated, twice daily, administered 12 hours apart, according to the approved label.
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults ≥ 18 years at Visit 1 * Subjects must be contractually capable and mentally able to understand and follow the instructions of the study personnel * Physician's diagnosis of chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype, except idiopathic pulmonary fibrosis (IPF) * Treatment with nintedanib in INREAL will be the first and only prescription of any antifibrotic treatment for each individual patient within this observational study after a physician's decision being made for this treatment option earlier * Outpatients not currently hospitalized with a life expectancy \> 12 months per investigator's assessment * Written informed consent prior to study participation * Current forced vital capacity (FVC) measurement (taken within the last 3 months) available in the patient file * Women of childbearing potential must take appropriate precautions against getting pregnant during the intake of nintedanib
Exclusion criteria
* Patients with contraindications according to Summary of Product Characteristics (SmPC) * Prior use of any antifibrotic treatment * Lack of informed consent * Pregnant or lactating females * Any physician diagnosed exacerbation of ILD in the patient's history file, irrespective of time since event * Current diagnosis of lung cancer * Respiratory failure (pH \< 7,35 and/ or respiratory rate \> 30/min) in the patient's history * Participation in a parallel interventional clinical trial * Patients being spouse or lateral relatives to the second degree or economically dependent from the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | At baseline and at week 52±6. | 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. |
| 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 | At baseline and at week 52±6. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | At baseline and at week 52±6. | 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. |
| 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 | At baseline and at week 52±6. | 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. |
| Absolute Change From Baseline in Living With Pulmonary Fibrosis Questionnaire (L-PF) Cough Symptom Score [Points] at Week 52 | 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 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. |
| Absolute Change From Baseline in Living With Pulmonary Fibrosis Questionnaire (L-PF) Dyspnea Symptom Score [Points] at Week 52 | 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. |
Countries
Germany
Participant flow
Recruitment details
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.
Pre-assignment details
Only patients that met all inclusion and none of the exclusion criteria were included.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 102 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 10 |
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Not treated | 6 |
| Overall Study | Other reasons than listed | 11 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Nintedanib-treated Patients | — |
|---|---|---|
| Age, Continuous | 70.47 Years STANDARD_DEVIATION 10.74 | — |
| Forced vital capacity (FVC) [% predicted] | 65.18 Percentage STANDARD_DEVIATION 18.86 | — |
| Living with pulmonary fibrosis questionnaire (L-PF) cough symptom score | 37.46 Units on a scale STANDARD_DEVIATION 25.67 | — |
| Living with pulmonary fibrosis questionnaire (L-PF) dyspnea symptom score | 24.71 Units on a scale STANDARD_DEVIATION 18.56 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 38 Participants | — |
| Sex: Female, Male Male | 64 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 102 |
| other Total, other adverse events | 45 / 102 |
| serious Total, serious adverse events | 16 / 102 |
Outcome results
Primary
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
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nintedanib-treated Patients | 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 |
p-value: 0.5135Z-test of correlation
Primary
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
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nintedanib-treated Patients | 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 |
p-value: 0.1185Z-test of correlation
Secondary
Absolute Change From Baseline in Living With Pulmonary Fibrosis Questionnaire (L-PF) Cough Symptom Score [Points] at Week 52
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib-treated Patients | 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
Absolute Change From Baseline in Living With Pulmonary Fibrosis Questionnaire (L-PF) Dyspnea Symptom Score [Points] at Week 52
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib-treated Patients | 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 |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nintedanib-treated Patients | 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 |
p-value: 0.3478Z-test of correlation
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nintedanib-treated Patients | 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 |
p-value: 0.0764Z-test of correlation