For a study, it was determined that because of the unprecedented clinical advantages seen with the new triple-combination CFTR (CF transmembrane regulator)–modulator medication elexacaftor/tezacaftor/ivacaftor (ETI), the care for people with cystic fibrosis (CF) who have at least one F508del mutation will change dramatically. The addition of ETI to the standard of care provides fresh motivation and opportunities to examine, lowering the overall treatment burden and determining whether other chronic drugs can now be safely withdrawn without sacrificing clinical benefit. SIMPLIFY was a master protocol that examined the effects of stopping vs. continuing two standard chronic therapies in persons with CF who are at least 12 years old and stable on ETI therapy.
The procedure consisted of two parallel randomized controlled studies meant to assess the independent short-term effects of quitting hypertonic saline or dornase alfa, allowing patients taking both medications to participate in one or both trials. The major goal of each trial was to see if stopping treatment after establishing ETI was non-inferior to continuing treatment, as measured by the 6-week absolute change in percent-predicted forced expiratory volume in 1 second. The research’s development necessitated striking a balance between ideal study design principles and practicalities. SIMPLIFY will be the largest multicenter, randomized, controlled drug withdrawal research yet conducted in the field of cystic fibrosis. The study was unique in giving timely evidence on whether the daily treatment load for CFTR-modulator medication can be decreased.
Reference:www.atsjournals.org/doi/abs/10.1513/AnnalsATS.202010-1336SD
