1. Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials.
- Author
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Mayer-Hamblett, Nicole, Ratjen, Felix, Russell, Renee, Donaldson, Scott, Riekert, Kristin, Sawicki, Gregory, Odem-Davis, Katherine, Young, Julia, Rosenbluth, Daniel, Taylor-Cousar, Jennifer, Goss, Christopher, Retsch-Bogart, George, Clancy, John, Genatossio, Alan, OSullivan, Brian, Berlinski, Ariel, Millard, Susan, Omlor, Gregory, Wyatt, Colby, Moffett, Kathryn, Nichols, David, and Gifford, Alex
- Subjects
Humans ,Cystic Fibrosis ,Cystic Fibrosis Transmembrane Conductance Regulator ,Deoxyribonuclease I ,Lung ,Saline Solution ,Hypertonic - Abstract
BACKGROUND: Reducing treatment burden is a priority for people with cystic fibrosis, whose health has benefited from using new modulators that substantially increase CFTR protein function. The SIMPLIFY study aimed to assess the effects of discontinuing nebulised hypertonic saline or dornase alfa in individuals using the CFTR modulator elexacaftor plus tezacaftor plus ivacaftor (ETI). METHODS: The SIMPLIFY study included two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials at 80 participating clinics across the USA in the Cystic Fibrosis Therapeutics Development Network. We included individuals with cystic fibrosis aged 12-17 years with percent predicted FEV1 (ppFEV1) of 70% or more, or those aged 18 years or older with ppFEV1 of 60% or more, if they had been taking ETI and either (or both) mucoactive therapies (≥3% hypertonic saline or dornase alfa) for at least 90 days before screening. Participants on both hypertonic saline and dornase alfa were randomly assigned to one of the two trials, and those on a single therapy were assigned to the applicable trial. All participants were then randomly assigned 1:1 to continue or discontinue therapy for 6 weeks using permuted blocks of varying size, stratified by baseline ppFEV1 (week 0; ≥90% or
- Published
- 2023