A Study Based on Medical Records in Spain That Looks at Diarrhoea Control in People With Pulmonary Fibrosis Who Are Taking Nintedanib

Observational, Multicentre, Prospective, Real-world Post-authorization Safety Study Describing the Achievement of Nintedanib-associated DIArrhoea Control After 12 Weeks of Follow-up in Patients With Idiopathic puLmonary FIBrosis (IPF) and Progressive Pulmonary Fibrosis (Other Than IPF) in Spain: the DIALFIB Study

This is an observational, non-interventional, and prospective post authorization safety study (PASS) that will describe the real-world proportion of patients that achieve nintedanib-associated diarrhoea control after 12 weeks of follow-up, in hospital settings in Spain. It will include outpatients (i.e., those attending ambulatory visits) with interstitial lung diseases (IPF) and other progressive pulmonary fibrosis (PPF) treated with nintedanib (150 mg bid) and having a first episode of diarrhoea after nintedanib initiation.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis; Diarrhoea
• Intervention / Treatment: Drug: Nintedanib

• Study Type: Observational
• Enrollment (Actual): 18

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Barcelona, Spain, 08916
    • Hospital Universitari Germans Trias i Pujol
  • Bizkaia, Spain, 48903
    • Hospital Universitario de Cruces
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de Las Nieves
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28006
    • Hospital de La Princesa
  • Pontevedra, Spain, 36312
    • Hospital Alvaro Cunqueiro
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Clinical management of interstitial lung diseases (IPF) or other progressive pulmonary fibrosis (PPF) patients who experienced nintedanib-associated diarrhoea.

Description

Inclusion criteria

1. Adults (≥18 years old) at diarrhoea initiation.
2. Ability to consent and to conduct all procedures of the study, as judged by the study investigator, and agreeing to participate providing informed consent at baseline.
3. Diagnosis of idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) (other than IPF), as registered in electronic medical records (EMR) using free text or international statistical classification of diseases and related health problems (ICD) codes (ICD-9 and/or ICD-10), at least 1 day before diarrhoea initiation.
4. Being treated with 150 milligram (mg) bid of nintedanib when initiating diarrhoea symptoms, defined as having a nintedanib anatomical therapeutic chemical (ATC) code (L01EX09) or the molecule/commercial name registered in the EMR, for at least 1 day before diarrhoea initiation.
5. First pulmonologist consultation (face-to-face) at the time of recruitment due to a first diarrhoea episode as defined by the pulmonologist since nintedanib initiation. Diarrhoea defined as the passage of three or more loose or liquid stools in a 24-hour period (loose or liquid stools defined as stools with a Bristol Stool Form Scale (BSFS) of 6 or 7 points).

Exclusion criteria

1. Patients diagnosed with systemic sclerosis associated interstitial lung disease (SSc-ILD) as registered in EMR using free text or ICD codes (ICD-9 and ICD-10). Referent to any time before or at diarrhoea initiation.
2. Participation in any clinical trial including a drug or device at any time before or at diarrhoea initiation.
3. Participation in any Patient Support Programme (PSP) at diarrhoea initiation.
4. Having history of chronic gastrointestinal disorder (e.g., inflammatory bowel disease or the short gut syndrome), pancreatic dysfunction/insufficiency, or colon cancer; due to the likelihood of faecal incontinence. Referent to any time before or at diarrhoea initiation.
5. Having a performance status (PS) ≥3 points on the Eastern Cooperative Oncology Group scale (ECOG) scale at diarrhoea initiation, due to the likelihood of faecal incontinence.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
IPF/PPF Participants; Participants with idiopathic pulmonary fibrosis (IPF) or other progressive pulmonary fibrosis (PPF) who experienced treatment-associated diarrhoea while being treated with 150 milligrams (mg) nintedanib twice daily. Participants were observed for 12 weeks from the time of first diarrhoea occurrence.	Drug: Nintedanib; Participants received 150 milligrams (mg) Nintedanib, twice daily.; Other Names: OFEV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of Diarrhoea Control at Week 12 Follow-up While Taking the Optimal Nintedanib Dose	The percentage of participants who achieved diarrhoea control while taking the optimal nintedanib dose (150 milligrams, twice a day) at 12-week follow-up referent to diarrhoea initiation is described. Achievement of diarrhoea control (yes/no) is defined as the passage of fewer than 3 loose or liquid stools in a 24-hour period. Loose or liquid stools were defined as stools with a Bristol Stool Form Scale (BSFS) score of 6 or 7. The BSFS classifies stool into seven categories based on their consistency. The scale ranges from 1 (hard, separate lumps) to 7 (entirely liquid), with scores 1 and 2 indicating constipation and scores 6 and 7 indicating diarrhoea.	12 weeks after baseline visit.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in the Proportion of Participants Taking the Optimal Nintedanib Dose at Week 12 Follow-up	The proportion of participants, presented as percentage, taking the optimal nintedanib dose (150 milligrams, twice a day) at 12-week follow-up referent to diarrhoea initiation is described.	12 weeks after baseline visit.
Absolute Change From Baseline in BSFS Score at Week 12 Follow-up	The absolute change in Bristol Stool Form Scale (BSFS) score at the 12-week follow-up, as compared to the baseline visit, is reported. The BSFS classifies stool into seven categories based on their consistency. The scale ranges from 1 (hard, separate lumps) to 7 (entirely liquid), with scores 1 and 2 indicating constipation and scores 6 and 7 indicating diarrhoea. The baseline value was measured referent to the day of diarrhoea initiation, while the Week 12 timepoint was measured as the mean value from the last 7 days.	At baseline and at Week 12.
Absolute Change From Baseline in Number of Stools Per Day at Week 12 Follow-up	The absolute change from baseline in number of stools per day at 12-week follow-up is reported. The baseline value was measured referent to the day of diarrhoea initiation, while the Week 12 timepoint value was collected as a mean number per patient in the last 7 days.	At baseline and at Week 12.
Absolute Change From Baseline in Current Body Weight at Week 12 Follow-up	The absolute change from baseline in current body weight (kilograms) at Week 12 follow-up is reported. The baseline value was measured referent to the day of diarrhoea initiation, while the Week 12 timepoint was measured as the mean value from the last 7 days.	At baseline and at Week 12.
Proportion of Participants Who Used Carob Flour for the Treatment of Nintedanib-associated Diarrhoea	The proportion of participants, presented as percentage, who used carob flour for the treatment of nintedanib-associated diarrhoea at any time from diarrhoea initiation to Week 12 follow-up is reported.	From baseline visit, up to 12 weeks.
Number of Participants Per Treatment Category for Nintedanib-associated Diarrhoea at Diarrhoea Initiation	The number of participants per treatment category for nintedanib-associated diarrhea is reported. Treatment categories of nintedanib-associated diarrhoea include pharmacological treatments (e.g., loperamide, oral rehydration salt formulations, tannate), non-pharmacological treatments (e.g., carob flour, zinc, probiotics, other dietary interventions, hydration), and a combination of both pharmacological and non-pharmacological treatments.	At baseline visit.
Number of Participants Per Treatment Category for Nintedanib-associated Diarrhoea at Week 12 Follow-up	The number of participants per treatment category for nintedanib-associated diarrhea is reported. Treatment categories of nintedanib-associated diarrhoea include pharmacological treatments (e.g., loperamide, oral rehydration salt formulations, tannate), non-pharmacological treatments (e.g., carob flour, zinc, probiotics, other dietary interventions, hydration), and a combination of both pharmacological and non-pharmacological treatments.	12 weeks after baseline visit.
Occurrence of at Least One Nintedanib Dose Reduction From Diarrhoea Initiation to Week 12 Follow-up	The occurrence of at least one nintedanib dose reduction is reported as the number of study participants, among those who changed their nintedanib dose, who had at least one dose reduction of nintedanib over the course of the study. Dose reduction is defined as a reduction from 150 milligrams, twice daily to 100 milligrams, twice daily.	From baseline visit, up to 12 weeks.
Occurrence of Permanent Withdrawal of Nintedanib	The occurrence of permanent withdrawal of nintedanib is reported as the number of participants who permanently withdrew nintedanib treatment between diarrhoea initiation and 12-week follow-up. Permanent withdrawal is defined as discontinuing nintedanib treatment (either 150 milligrams or 100 milligrams, twice daily) and not reintroducing it before the 12-week follow-up.	From baseline visit, up to 12 weeks
Occurrence of at Least One Nintedanib Dose Escalation From Diarrhoea Initiation to 12-week Follow-up	The occurrence of at least one nintedanib dose escalation is reported as the number of participants who had at least one nintedanib dose escalation from diarrhoea initiation to 12-week follow-up. Dose escalation is defined as an increase of nintedanib dose from 100 milligrams to 150 milligrams, twice daily.	From baseline visit, up to 12 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2024
• Primary Completion (Actual): April 29, 2025
• Study Completion (Actual): April 29, 2025

Study Registration Dates

• First Submitted: December 29, 2023
• First Submitted That Met QC Criteria: December 29, 2023
• First Posted (Actual): January 11, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Pulmonary Fibrosis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Idiopathic Pulmonary Fibrosis; Diarrhea; nintedanib
• Other Study ID Numbers: 1199-0545

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Once the criteria in section 'time frame frame' are fulfilled, researchers can use the following link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can 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.
• IPD Sharing Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• 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 the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal 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