CFTR Modulators and Gastrointestinal Complications (CFTR-MAGIC)

NHS Trust

Status

Completed

Conditions

Gastrointestinal System Disease

Lung Diseases

Pancreatic Enzyme Abnormality

Distal Intestinal Obstruction Syndrome

Pancreatic Disease

Cystic Fibrosis

Digestive System Disease

Treatments

Other: No intervention

Study type

Observational

Funder types

Other

Identifiers

NCT05253859

CFTR-MAGIC

Details and patient eligibility

About

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.

Full 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.

Enrollment

47,023 patients

Sex

All

Volunteers

No Healthy Volunteers

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.