CFTR Modulators and Gastrointestinal Complications

NCT05253859 | Completed

• 1 other identifier: CFTR-MAGIC
• Study Type: observational
• Target: 47,023
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (3)

• Describe DIOS events and PERT usage in UK and US registries 2007-2018

  Descriptive analysis to include cumulative incidence of DIOS and prevalence of PERT usage in the UK and US. PERT use will be dichotomised (i.e use/no use), incidence of DIOS (event/no event), plotted by year, separated by registry. Trends will be described according to age range (\<6, 6-11, 12+), sex, BMI, ethnicity, antibiotic use, gastrointestinal co-morbidities and FEV1 lung function. These demographics will also be used for demographic propensity matching to define a control group of non-eligible non-users of CFTR modulators that are otherwise representative of the CFTR modulator user group the year that the CFTR modulator exposure was commenced.

  2 years

• Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: population level controlled interrupted time series (ITS)

  This will investigate the effect of CFTR modulator intervention on the rate on PERT use and DIOS incidence. ITS will explore proportion of DIOS events at population level in the CFTR modulator population and the propensity score defined comparator population. ITS will explore proportion of overall PERT usage (user/non user), and the proportion of individuals with a reduction in weight standardised PERT dose (decrease/no decrease).

  2 years

• Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: patient-level time series

  This will focus on patient level associations to complement the registry level findings. Associations in the incidence of PERT usage and DIOS events from 2012 in individuals taking CFTR modulators, compared to propensity matched controls will be explored. DIOS events: Multilevel Poisson Regression model for count data by year, incidence rate ratio (frequency of DIOS events). Adjusted analysis for main covariates. PERT use: Multilevel linear regression for continuous data, multilevel logistic regression for dichotomised data. Adjusted for main covariates.

  2 years

Study Arms (2)

Cystic fibrosis registry (UK)

People with cystic fibrosis registered in the UK CF registry

Other: No intervention

Cystic fibrosis registry (US)

People with cystic fibrosis registered in the US CF registry

Other: No intervention

Interventions

No intervention OTHER

Registry study: No intervention

Cystic fibrosis registry (UK); Cystic fibrosis registry (US)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• \- 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.

Sponsors & Collaborators

• Nottingham University Hospitals NHS Trust: lead
• The Leeds Teaching Hospitals NHS Trust: collaborator
• Royal Brompton & Harefield NHS Foundation Trust: collaborator
• University of Washington: collaborator
• Seattle Children's Hospital: collaborator

Study Sites (1)

Nottingham University Hospitals NHS Trust

Nottingham, NG7 2UH, United Kingdom

Location

Related Links

• Original article. "Pancreatic enzyme prescription following ivacaftor licensing: A retrospective analysis of the US and UK cystic fibrosis registries"

MeSH Terms

Conditions

Cystic Fibrosis; Digestive System Diseases; Pancreatic Diseases; Lung Diseases

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Alan Smyth

  Nottingham University Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: February 24, 2022
• Study Start: October 1, 2021
• Primary Completion: February 10, 2024
• Study Completion: February 10, 2024
• Last Updated: July 3, 2024

Record last verified: 2023-07

Locations

GB (1)