Symptom Based Performance of Airway Clearance After Starting Highly Effective Modulators for Cystic Fibrosis (SPACE-CF)

Summary

Cystic Fibrosis (CF) is an autosomal recessive disease cause by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) manifesting in multiple organs, the most common cause of morbidity and mortality continues to be the pulmonary manifestation. CFTR dysfunction leads to reduced mucociliary clearance, impaired innate immune system function in the lungs (within the airway surface liquid \[ASL\] lining the epithelial barrier of the lungs) and reduced ASL hydration (stickier mucus). To try and help correct this underlying defect patients have been performing airway clearance for decades using different techniques (Percussion and postural drainage \[P\&PD\], Positive expiratory pressure \[PEP\], Oscillatory positive expiratory pressure \[OPEP\], High-frequency chest compression \[HFCC\], exercise), inhaled mucolytics (Hypertonic Saline, Pulmozyme) and inhaled antibiotics. However, performing daily airway clearance can be a large burden on patients and their families with a median number of daily therapies around 7 and average time spent on therapies at almost 2 hours daily. This high treatment burden leads many patients to have reduced adherence to their regimens and multiple studies have shown around 20% of patients performing no daily airway clearance. Since the release of highly effective CFTR modulator therapy patients have experienced improvements in lung function measurements and imaging-based ventilation measurements, reduction in pulmonary exacerbations, and improvement in daily symptom scores. Over 80% of patients and their families and over 95% of clinicians in the United States support the idea of trials looking into the simplification of airway clearance regimens. Combining the inability of most patients to complete their daily regimens, patient and clinician interest in treatment simplification research, and the overwhelming cost of most inhaled medications in cystic fibrosis with the improvement in mucociliary transport and symptoms with highly effective modulator therapy suggests a research program aimed at reducing the treatment burden of daily airway clearance should be considered. The investigators propose the following: determine if there is additional benefit in continuous airway clearance regimens after starting Elexacaftor-Tezacaftor-Ivacaftor (ETI) and if so, is this benefit noticeable on pulmonary function testing and imaging.

Conditions

• Cystic Fibrosis
• Mucociliary Clearance Defect

Interventions

OTHER

Symptom driven performance of airway clearance

Perform symptom driven/intermittent airway clearance therapy with frequency based off of patient's daily symptoms including mobilization therapy (high-frequency chest compression or vest device, intrapulmonary percussive ventilator, positive expiratory pressure device) and inhaled/nebulized therapies of albuterol, hypertonic saline and dornase alfa for the 12 week study period.

OTHER

Continuous daily performance of airway clearance

Continue run-in protocol of twice daily airway clearance using twice daily mobilization therapy (high-frequency chest compression or vest device, intrapulmonary percussive ventilator, positive expiratory pressure device) and inhaled/nebulized therapies of albuterol, hypertonic saline and dornase alfa for the 12 week study period.

Sponsors & Collaborators

• University of Missouri-Columbia

  lead OTHER

Principal Investigators

• Zach Holliday, MD · University of Missouri School of Medicine

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-09-05

Primary Completion

2024-09-18

Completion

2024-09-18

Countries

• United States

Study Locations