Evaluating the Impact of Stopping Chronic Therapies after Modulator Drug Therapy in Cystic Fibrosis: The SIMPLIFY Clinical Trial Study Design.

Autor: Mayer-Hamblett N; Cystic Fibrosis Therapeutics Development Network Coordinating Center, Seattle Children's Hospital, Seattle, Washington.; Department of Pediatrics and.; Department of Biostatistics, University of Washington, Seattle, Washington., Nichols DP; Cystic Fibrosis Therapeutics Development Network Coordinating Center, Seattle Children's Hospital, Seattle, Washington.; Department of Pediatrics and., Odem-Davis K; Cystic Fibrosis Therapeutics Development Network Coordinating Center, Seattle Children's Hospital, Seattle, Washington., Riekert KA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland., Sawicki GS; Division of General Pediatrics and Respiratory Diseases, Boston Children's Hospital, Boston, Massachusetts.; Department of Pediatrics, Harvard Medical School, Harvard University, Boston, Massachusetts., Donaldson SH; Division of Pulmonary and Critical Care Medicine and., Ratjen F; Division of Respiratory Translational Medicine Program, SickKids Research Institute, Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada., Konstan MW; Department of Pediatrics, Rainbow Babies and Children's Hospital and School of Medicine, Case Western Reserve University, Cleveland, Ohio., Simon N; Cystic Fibrosis Therapeutics Development Network Coordinating Center, Seattle Children's Hospital, Seattle, Washington.; Department of Biostatistics, University of Washington, Seattle, Washington., Rosenbluth DB; Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, Washington University, St. Louis, Missouri., Retsch-Bogart G; Division of Pediatric Pulmonology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina., Clancy JP; Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.; Cystic Fibrosis Foundation, Bethesda, Maryland., VanDalfsen JM; Cystic Fibrosis Therapeutics Development Network Coordinating Center, Seattle Children's Hospital, Seattle, Washington., Buckingham R; Cystic Fibrosis Therapeutics Development Network Coordinating Center, Seattle Children's Hospital, Seattle, Washington., Gifford AH; Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; and.; The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire.
Jazyk: angličtina
Zdroj: Annals of the American Thoracic Society [Ann Am Thorac Soc] 2021 Aug; Vol. 18 (8), pp. 1397-1405.
DOI: 10.1513/AnnalsATS.202010-1336SD
Abstrakt: The care for individuals with cystic fibrosis (CF) with at least one F508del mutation will greatly change as a result of the unparalleled clinical benefits observed with the new triple-combination CFTR (CF transmembrane regulator)-modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI). Incorporating ETI into the standard of care creates new motivation and opportunity to consider reductions in overall treatment burden and evaluate whether other chronic medications can now be safely discontinued without loss of clinical benefit. SIMPLIFY is a master protocol poised to test the impact of discontinuing versus continuing two commonly used chronic therapies in people with CF who are at least 12 years of age or older and stable on ETI therapy. The protocol is composed of two concurrent randomized controlled trials designed to evaluate the independent short-term effects of discontinuing hypertonic saline or dornase alfa, enabling individuals on both therapies to participate in one or both trials. The primary objective for each trial is to determine whether discontinuing treatment is noninferior to continuing treatment after establishment of ETI, as measured by the 6-week absolute change in the percent-predicted forced expiratory volume in 1 second. Developing this study required a balance between ideal study-design principles and feasibility. SIMPLIFY will be the largest multicenter, randomized, controlled medication-withdrawal study in CF. This study is uniquely positioned to provide timely evidence on whether the daily treatment burden can be reduced among individuals on CFTR-modulator therapy. Clinical trial registered with www.clinicaltrials.gov (NCT04378153).
Databáze: MEDLINE