Clinical trial NCT05253859: CFTR Modulators and Gastrointestinal Complications
Official title: CFTR Modulators and Gastrointestinal Complications
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cystic Fibrosis
Gastrointestinal System Disease
Distal Intestinal Obstruction Syndrome
Pancreatic Enzyme Abnormality
Pancreatic Disease
Lung Diseases
Digestive System Disease
Keywords: Cystic fibrosis
Distal Intestinal Obstruction Syndrome
Pancreatic enzyme replacement therapy
Gastrointestinal symptoms
Gut symptoms
Lead sponsor: Nottingham University Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: The Leeds Teaching Hospitals NHS Trust
name: Royal Brompton & Harefield NHS Foundation Trust
name: University of Washington
name: Seattle Children's Hospital
First posted: 2022-02-24
Enrollment: 47023
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children, adolescents and adults with a diagnosis of cystic fibrosis whose data are registered on either the UK or US cystic fibrosis registries.

Brief summary: To elucidate the similarities and distinctions in non-pulmonary manifestations of cystic fibrosis (CF) including distal intestinal obstruction syndrome (DIOS) incidence and pancreatic enzyme replacement therapy (PERT) use between US and UK CF populations in a parallel study using data from the UK and US CF registries. To assess how CFTR modulators impacted upon recorded PERT use and incidence of DIOS.

Detailed description: Cystic fibrosis (CF) is a autosomal recessive multi-system disorder caused by mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene. As well as the documented respiratory complications of CF, gastrointestinal manifestations are of clinical importance. CFTR mutations in the gastrointestinal tract are responsible for pancreatic exocrine insufficiency in around 85% of people with CF (pwCF). In addition a severe gastrointestinal complication in CF is distal intestinal obstructive syndrome (DIOS), affecting 5.7% pwCF in the UK (2.5% in \<16 years and 7.7% in adults) and 2.1% in the US (\<18 years 1.7%, adult 2.4%) in 2019.

This is a parallel data registry study using data from the UK and US CF registries, with data provided for the time period 2007-2018. As such no individual participants will be recruited to the study. The CFTR modulators to be studies are Ivacaftor and lumacaftor/ivacaftor.

Study aims;

* Describe DIOS events and PERT usage in UK and US registries
* Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: population time series
* Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: patient-level time series

The outcomes of the above aims will be used to generate hypotheses regarding the effect of the newer CFTR modulators such as Symdeko/Symkevi and Tricaftor/Kaftrio on PERT usage and DIOS incidence in CF registry data post 2018. This will form the basis of future studies.

Eligibility criteria: Inclusion Criteria:

* All patients with CF of any genotype on the UK and US cystic fibrosis registries from the period 2007 - 2018.

Exclusion Criteria:

- Patients whose CFTR modulator status is unknown or only have one year of CFTR data recorded on the registry will be excluded from the analysis of the effects of CFTR modulators. This is to account for the fact that DIOS data is annualised on the registries, therefore there is no certainty at what time of year DIOS was diagnosed in relation to commencing CFTR modulator therapy.

Primary outcomes:
measure: Describe DIOS events and PERT usage in UK and US registries 2007-2018
timeFrame: 2 years
measure: Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: population level controlled interrupted time series (ITS)
timeFrame: 2 years
measure: Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: patient-level time series
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
Study officials:
affiliation: Nottingham University Hospitals NHS Trust
name: Alan Smyth
role: PRINCIPAL_INVESTIGATOR
References: