title: Design and Rationale of the Reevaluation of Systemic Early Neuromuscular Blockade Trial for Acute Respiratory Distress Syndrome.
abstract: The Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial is a multicenter, randomized trial designed to assess the efficacy and safety of early neuromuscular blockade in patients with moderate to severe acute respiratory distress syndrome. This document provides background for interpretation of the trial results, and highlights unique design approaches that may inform future trials of acute illness. We describe the process by which ROSE was chosen as the inaugural trial of the multidisciplinary Prevention and Early Treatment of Acute Lung Injury Network, provide the trial methodology using the Consolidated Standards of Reporting Trials framework, and discuss key design challenges and their resolution. Four key design issues proved challenging-feasibility, choice of sedation depth in the control group, impact of emphasizing early treatment on enrollment criteria and protocol execution, and choice of positive end-expiratory pressure strategy. We used literature, an iterative consensus model, and internal surveys of current practice to inform design choice. ROSE will provide definitive, Consolidated Standards of Reporting Trials adherent data on early neuromuscular blockade for future patients with acute respiratory distress syndrome. Our multidisciplinary approach to trial design may be of use to other trials of acute illness. Clinical trial registered with www.clinicaltrials.gov (NCT02509078).
authors: 1 University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: David T
authors: http://orcid.org/0000-0001-7649-1633
authors: DT
authors: Huang
authors: 1 University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Derek C
authors: DC
authors: Angus
authors: 2 University of Colorado, Denver, Colorado.
authors: Marc
authors: M
authors: Moss
authors: 3 Harvard Medical School, Boston, Massachusetts.
authors: B Taylor
authors: BT
authors: Thompson
authors: 4 University of Toronto, Toronto, Ontario, Canada.
authors: Niall D
authors: ND
authors: Ferguson
authors: 2 University of Colorado, Denver, Colorado.
authors: Adit
authors: A
authors: Ginde
authors: 5 Albert Einstein College of Medicine, New York, New York.
authors: Michelle Ng
authors: MN
authors: Gong
authors: 6 University of Washington, Seattle, Washington.
authors: Stephanie
authors: S
authors: Gundel
authors: 3 Harvard Medical School, Boston, Massachusetts.
authors: Douglas L
authors: DL
authors: Hayden
authors: 7 Cleveland Clinic, Cleveland, Ohio.
authors: R Duncan
authors: RD
authors: Hite
authors: 3 Harvard Medical School, Boston, Massachusetts.
authors: Peter C
authors: PC
authors: Hou
authors: 6 University of Washington, Seattle, Washington.
authors: Catherine L
authors: CL
authors: Hough
authors: 8 University of Michigan, Ann Arbor, Michigan; and.
authors: Theodore J
authors: TJ
authors: Iwashyna
authors: 9 University of California, San Francisco, San Francisco, California.
authors: Kathleen D
authors: KD
authors: Liu
authors: 3 Harvard Medical School, Boston, Massachusetts.
authors: Daniel S
authors: DS
authors: Talmor
authors: 1 University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Donald M
authors: DM
authors: Yealy
mesh_terms: D001279:Atracurium / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002423:Cause of Death; D005240:Feasibility Studies; D006801:Humans; D011939:Mental Recall; D009026:Mortality; D053580:Muscle Strength; D019148:Neuromuscular Blockade / Q000379:methods*; D009466:Neuromuscular Blocking Agents / Q000627:therapeutic use*; D011175:Positive-Pressure Respiration; D012121:Respiration, Artificial / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000628:therapy*
chemical_list: D009466:Neuromuscular Blocking Agents; D001279:Atracurium; C101584:cisatracurium
keywords: adult; clinical trial; interdisciplinary communication; methods; respiratory distress syndrome