Design and powering of cystic fibrosis clinical trials using pulmonary exacerbation as an efficacy endpoint

Background: Reduction in pulmonary exacerbations is an important efficacy endpoint for CF clinical studies. Powering exacerbation endpoints requires estimation of the future exacerbation incidence in CF study populations, but rates differ across the population. Methods: We have estimated exacerbation rates for Epidemiologic Study of CF subpopulations stratified by age, FEV₁% predicted, sex, weight-for-age percentile, respiratory signs and symptoms, and history of exacerbation and bacterial culture. Sample sizes required to attain 80% power to detect exacerbation reductions of 20% to 80% in 1:1 randomized studies of 3 to 12month duration were determined. Exacerbation treatments with "any" antibiotic (new oral quinolone, new inhaled antibiotic, or intravenous (IV) antibiotic) and with IV antibiotics were studied. Results: At all ages, decreased FEV₁, female sex, exacerbation history, and Pseudomonas aeruginosa culture history were associated with increased treatment for exacerbation. Conclusions: These data should assist investigators in the design of future CF exacerbation studies.