A Pilot Randomized Trial of Pediatric Cystic Fibrosis Pulmonary Exacerbations Treatment Strategies

Despite the high prevalence and clear morbidity of cystic fibrosis (CF) pulmonary exacerbations (PEx), there have been no published clinical trials of outpatient exacerbation management.To assess the feasibility of a pediatric clinical trial in which treatment of a mild PEx is assigned randomly to immediate oral antibiotics or "tailored therapy" (increased airway clearance alone with oral antibiotics added only for pre-specified criteria). The outcome on which sample size was based was the proportion of tailored therapy participants who avoided oral antibiotics during the 28 days following randomization.In this randomized open-label pilot feasibility study at 10 US sites, children ages 6 to 18 years with CF were enrolled at their well baseline and followed through their first randomized PEx.121 participants were enrolled, among whom 94 (78%) reported PEx symptoms at least once; among these, 81 (86%) had at least one PEx that met randomization criteria of which 63 (78%) were randomized. Feasibility goals were met, including enrollment, early detection of PEx symptoms and ability to randomize. Among the 33 participants assigned to tailored therapy, 10 (30%) received oral antibiotics, while 29/30 (97%) assigned to immediate antibiotics received oral antibiotics. The avoidance of oral antibiotics in 70 (95% CI 54, 85)% was statistically significantly different from our null hypothesis that <10% of participants assigned to the tailored therapy arm would avoid antibiotics.Our pilot study demonstrates that conducting a randomized trial of oral antibiotic treatment strategies for mild pulmonary exacerbations in children with CF is feasible and that assignment to a tailored therapy arm may reduce antibiotic exposure.clinicaltrials.gov NCT04608019 Primary source of funding: Cystic Fibrosis Foundation.