An 8 week open-label interventional multicenter study to explore the lung clearance index as endpoint for clinical trials in cystic fibrosis patients >= 8 years of age, chronically infected withPseudomonas aeruginosa

Sutharsan, Sivagurunathan; Naehrig, Susanne; Mellies, Uwe; Sieder, Christian und Ziegler, Jörg (2020): An 8 week open-label interventional multicenter study to explore the lung clearance index as endpoint for clinical trials in cystic fibrosis patients >= 8 years of age, chronically infected withPseudomonas aeruginosa. In: BMC Pulmonary Medicine, Bd. 20, Nr. 1, 167

Abstract

Background: Forced expiratory volume in 1 second (FEV1) is the only parameter currently recognized as a surrogate endpoint in cystic fibrosis (CF) trials. However, FEV(1)is relatively insensitive to changes in the small airways of patients with milder lung disease. This pilot study aimed to explore the lung clearance index (LCI) as a marker for use in efficacy trials with inhaled antibiotics in CF. Methods This open-label, single-arm study enrolled CF patients withPseudomonas aeruginosainfection, who were treated with tobramycin (28-day on/off regime). FEV1, LCI and bacterial load in sputum (CFU) were assessed at baseline, after 1, 4 and 8 weeks of treatment. Results All patients (n = 17) showed elevated LCI of > 11 despite 3 patients having normal FEV1(> 90% predicted) at baseline. Overall, LCI improved in 8 (47%) patients and FEV(1)in 9 (53%) patients. At week 4, LCI improved by 0.88, FEV(1)increased by 0.52%, andP. aeruginosareduced by 30,481.3 CFU/mL. These changes were however statistically non-significant. Six adverse events occurred in 5/17 (29.4%) patients, most of which were mild-to-moderate in severity. Conclusions: Due to the low evaluable sample size, no specific trend was observed related to the changes between LCI, FEV(1)and CFU. Based on the individual data from this study and from recently published literature, LCI has been shown to be a more sensitive parameter than FEV(1)for lung function. LCI can be hypothesized to be an appropriate endpoint for efficacy trials in CF patients if the heterogeneity in lung function is limited by enrolling younger patients or patients with more milder lung disease and thus, limiting the ventilation inhomogeneities.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1471-2466
• Sprache: Englisch