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

• Nintedanib (Drug), also known as OFEV: Participants received 150 milligrams (mg) Nintedanib, twice daily.

Primary outcomes

• Achievement of Diarrhoea Control at Week 12 Follow-up While Taking the Optimal Nintedanib Dose [12 weeks after baseline visit.]: 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.

Secondary outcomes

• Absolute Change in the Proportion of Participants Taking the Optimal Nintedanib Dose at Week 12 Follow-up [12 weeks after baseline visit.]: 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.
• Absolute Change From Baseline in BSFS Score at Week 12 Follow-up [At baseline and at Week 12.]: 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.
• Absolute Change From Baseline in Number of Stools Per Day at Week 12 Follow-up [At baseline and at Week 12.]: 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.
• Absolute Change From Baseline in Current Body Weight at Week 12 Follow-up [At baseline and at Week 12.]: 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.
• Proportion of Participants Who Used Carob Flour for the Treatment of Nintedanib-associated Diarrhoea [From baseline visit, up to 12 weeks.]: 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.
• Number of Participants Per Treatment Category for Nintedanib-associated Diarrhoea at Diarrhoea Initiation [At baseline visit.]: 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.
• Number of Participants Per Treatment Category for Nintedanib-associated Diarrhoea at Week 12 Follow-up [12 weeks after baseline visit.]: 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.
• Occurrence of at Least One Nintedanib Dose Reduction From Diarrhoea Initiation to Week 12 Follow-up [From baseline visit, up to 12 weeks.]: 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.
• Occurrence of Permanent Withdrawal of Nintedanib [From baseline visit, up to 12 weeks]: 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.
• Occurrence of at Least One Nintedanib Dose Escalation From Diarrhoea Initiation to 12-week Follow-up [From baseline visit, up to 12 weeks]: 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.

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• Absolute Change in the Proportion of Participants Taking the Optimal Nintedanib Dose at Week 12 Follow-up (Secondary), Number, Percentage of participants: IPF/PPF Participants 76.47
• Absolute Change From Baseline in BSFS Score at Week 12 Follow-up (Secondary), Mean, Score on a scale: IPF/PPF Participants -1.76 +/- 1.60
• Absolute Change From Baseline in Number of Stools Per Day at Week 12 Follow-up (Secondary), Mean, Stools per day: IPF/PPF Participants -2.09 +/- 1.27
• Absolute Change From Baseline in Current Body Weight at Week 12 Follow-up (Secondary), Mean, Kilograms: IPF/PPF Participants -0.66 +/- 1.93
• Proportion of Participants Who Used Carob Flour for the Treatment of Nintedanib-associated Diarrhoea (Secondary), Number, Percentage of participants: IPF/PPF Participants 88.24
• Number of Participants Per Treatment Category for Nintedanib-associated Diarrhoea at Diarrhoea Initiation (Secondary), Count of participants, Participants: IPF/PPF Participants 0
• Number of Participants Per Treatment Category for Nintedanib-associated Diarrhoea at Week 12 Follow-up (Secondary), Count of participants, Participants: IPF/PPF Participants 1
• Occurrence of at Least One Nintedanib Dose Reduction From Diarrhoea Initiation to Week 12 Follow-up (Secondary), Count of participants, Participants: IPF/PPF Participants 4
• Occurrence of Permanent Withdrawal of Nintedanib (Secondary), Count of participants, Participants: IPF/PPF Participants 4
• Occurrence of at Least One Nintedanib Dose Escalation From Diarrhoea Initiation to 12-week Follow-up (Secondary), Count of participants, Participants: IPF/PPF Participants 4
• Achievement of Diarrhoea Control at Week 12 Follow-up While Taking the Optimal Nintedanib Dose (Primary), Number, Percentage of participants: IPF/PPF Participants 70.59

Adverse events

Time frame: From baseline visit until end of follow-up, up to 94 days.

Other adverse events by term

• Study Protocol (PDF, 2024-10-29)
• Statistical Analysis Plan (PDF, 2025-02-28)