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 (INREAL)

Prospective Observational Investigation of Possible Correlations Between Change in FVC and Change in Cough or Dyspnea Scores Using the Living With Pulmonary Fibrosis Questionnaire (L-PF) Between Baseline and After Approximately 52 Weeks of Nintedanib Treatment in Patients Suffering From Chronic Fibrosing ILD With a Progressive Phenotype

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)).

Study Overview

• Status: Completed
• Conditions: Lung Diseases, Interstitial
• Intervention / Treatment: Drug: Nintedanib

• Study Type: Observational
• Enrollment (Actual): 108

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52071
    • Universitätsklinikum Aachen, AöR
  • Bad Homburg, Germany, 61350
    • Pneumologische Praxis Dr. Löh
  • Bad Kreuznach, Germany, 55543
    • ACURA Kliniken Rheinland-Pfalz
  • Berlin, Germany, 12351
    • Vivantes Klinikum Neukölln
  • Braunschweig, Germany, 38126
    • Klinikum Braunschweig
  • Chemnitz, Germany, 09116
    • Klinikum Chemnitz
  • Coswig, Germany, 01649
    • Fachkrankenhaus Coswig GmbH
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Essen, Germany, 45239
    • Ruhrlandklinik Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
  • Frankfurt, Germany, 60389
    • Praxis Dr. med. Claus Keller
  • Halle, Germany, 06120
    • Krankenhaus Martha-Maria Halle-Dölau
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Heidelberg, Germany, 69126
    • Universitätsklinikum Heidelberg Thoraxklinik Heidelberg Zentrum für interstitielle und seltene Lungenerkrankungen
  • Hemer, Germany, 58675
    • Lungenklinik Hemer in der Trägerschaft der Deutschen Gemeinschafts-Diakonieverband GmbH
  • Herne, Germany, 44649
    • Rheumazentrum Herne
  • Köln, Germany, 51109
    • Kliniken der Stadt Köln
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig
  • Lemgo, Germany, 32657
    • Klinikum Lippe
  • Minden, Germany, 32429
    • Johannes Wesling Klinikum Minden der Mühlenkreiskliniken AöR
  • Solingen, Germany, 42699
    • Wissenschaftliches Institut Bethanien für Pneumologie e.V.
  • Wuppertal, Germany, 42283
    • Petrus-Krankenhaus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

In this NIS, data on the effect of nintedanib in chronic fibrosing ILD with progressive phenotype in about 100 patients will be collected in routine clinical practice by ca. 20 specialists, experienced in treating ILD patients, (e. g. pulmonologists and rheumatologists) throughout Germany.

Patients to be recruited within this study have to have a physician diagnosed chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype (except idiopathic pulmonary fibrosis (IPF)), for which nintedanib is an indicated treatment.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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.

Drug: Nintedanib; 150 or 100 milligrams (mg) of nintedanib, when 150 mg is not tolerated, twice daily, administered 12 hours apart, according to the approved label.; Other Names: Ofev®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At baseline and at week 52±6.
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.	At baseline and at week 52±6.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At baseline and at week 52±6.
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.	At baseline and at week 52±6.
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.	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.
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.	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.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Andrea Marseille, +4961327714188, andrea.marseille@boehringer-ingelheim.com

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2021
• Primary Completion (Actual): April 9, 2024
• Study Completion (Actual): April 9, 2024

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: January 7, 2021
• First Posted (Actual): January 11, 2021

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Lung Diseases; Lung Diseases, Interstitial; Dyspnea; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Nintedanib
• Other Study ID Numbers: 1199-0449

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.
• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No