Effectiveness of CFTR Modulators According to Co-therapy (MODUCO)

Is Effectiveness of CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) Modulators Impacted by Co-therapy? A Population-based Comparative Effectiveness Study Using Data From French Cystic Fibrosis Registry Linked to French National Healthcare Insurance Database

Unless CFTR modulators are highly effective, the introduction of CFTR (Cystic fibrosis transmembrane conductance regulator) modulators could lead to concomitant reduction or discontinuation of respiratory co-therapies in real-life. Such reduction/discontinuation of respiratory co-therapies could lead to an overall decrease of the effectiveness of CF care.

MODUCO study aims: 1) to compare the clinical effectiveness on lung function and pulmonary exacerbation of CFTR modulator during the year of initiation, according to level of co-therapy among CF patients; 2) to describe the nature and level of respiratory co-therapies (azithromycin, RhDNase, inhaled antibiotics) in the year before the initiation of CFTR modulator; 3) to describe the changes in respiratory co-therapies during the first and the second year following the initiation of CFTR modulator and compare between the two CFTR modulators; 4) to describe adherence to CFTR modulator during the first and the second year following its initiation; 5) to study the association between the nature of respiratory co-therapies and adherence to CFTR modulator during the first and the second year following its initiation.

A national population-based comparative effectiveness study will be conducted, based on retrospective analysis of clinical and prescription data of the French CF registry linked with the French national health data system (SNDS).

Study Overview

• Status: Not yet recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Discontinuation of respiratory co-therapy (azithromycin, RhDNase, or inhaled antibiotics)

• Study Type: Observational
• Enrollment (Anticipated): 1990

Contacts and Locations

• Study Contact: Name: Isabelle DURIEU, MD; Phone Number: 0033 (0)4 78 86 13 52; Email: isabelle.durieu@chu-lyon.fr
• Study Contact Backup: Name: Marie VIPREY, MD; Phone Number: 0033 (0)4 72 11 51 39; Email: marie.viprey@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Exhaustive on the recruitment of the all french CF patients meeting with eligibility criteria.

Description

Inclusion Criteria:

• - CF patients aged 6 years and more,
• Treated at least 6 months by ivacaftor or lumacaftor/ivacaftor or elexacaftor/tezacaftor/ivacaftor,
• Included in the French CF registry,
• For whom probabilistic matching with the SNDS database has succeeded.

Exclusion Criteria:

• none

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Exposed group; Patients treated with CFTR modulator with at least the discontinuation of one respiratory co-therapy (azithromycin, RhDNase, or inhaled antibiotics) during the year of initiation (A0) of CFTR modulator.	Drug: Discontinuation of respiratory co-therapy (azithromycin, RhDNase, or inhaled antibiotics); Discontinuation or reduction of at least one respiratory co-therapy (azithromycin, RhDNase, or inhaled antibiotics)
Control group; Patients treated with CFTR modulator without any discontinuation of respiratory co-therapy (azithromycin, RhDNase, inhaled antibiotics) during the year of initiation (A0) of CFTR modulator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung function	Change in the best forced expiratory volume in 1 second (FEV1) % predicted, measured during the year (A+1) compared to the year of initiation (A0) of CFTR modulator. The best FEV1 of the year is collected annually in the French CF Registry.	two years

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: December 15, 2022
• First Submitted That Met QC Criteria: December 15, 2022
• First Posted (Actual): December 23, 2022

Study Record Updates

• Last Update Posted (Actual): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; CFTR modulators; co-therapy; SNDS
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: 69HCL20_0066

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No