Diarrhoea, Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
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.
Interventions
DRUGNintedanib
Participants received 150 milligrams (mg) Nintedanib, twice daily.
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
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Spain
Participant flow
Recruitment details
This was an observational, post authorization safety study based on newly collected data in patients in Spain with idiopathic pulmonary fibrosis (IPF) and other progressive pulmonary fibrosis (PPF) who were treated with 150 milligrams (mg) of nintedanib twice daily and had suffered a first episode of nintedanib-associated diarrhoea. The study baseline was the first pulmonologist visit due to a first episode of diarrhoea after the initiation of nintedanib treatment.
Pre-assignment details
All participants were screened for eligibility prior to participation in the trial. Participants attended a specialist site which ensured that they (the participants) strictly met all inclusion and none of the exclusion criteria. During the recruitment period, 20 participants were initially screened, with 18 considered for enrollment. One participant was excluded from the analysis set due to not fulfilling all inclusion criteria.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 70.28 Years STANDARD_DEVIATION 6.88 |
| Race/Ethnicity, Customized Black | 1 Participants |
| Race/Ethnicity, Customized Latino | 1 Participants |
| Race/Ethnicity, Customized White | 16 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 2 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
None listed