title: Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome.
abstract: BACKGROUND
  Despite advances in supportive care, moderate-severe acute respiratory distress syndrome (ARDS) is associated with high mortality rates, and novel therapies to treat this condition are needed. Compelling pre-clinical data from mouse, rat, sheep and ex vivo perfused human lung models support the use of human mesenchymal stem (stromal) cells (MSCs) as a novel intravenous therapy for the early treatment of ARDS.
  
  
  METHODS
  This article describes the study design and challenges encountered during the implementation and phase 1 component of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of bone marrow-derived human MSCs for moderate-severe ARDS. A trial enrolling 69 subjects is planned (9 subjects in phase 1, 60 subjects in phase 2 treated with MSCs or placebo in a 2:1 ratio).
  
  
  RESULTS
  This report describes study design features that are unique to a phase 1 trial in critically ill subjects and the specific challenges of implementation of a cell-based therapy trial in the ICU.
  
  
  CONCLUSIONS
  Experience gained during the design and implementation of the START study will be useful to investigators planning future phase 1 clinical trials based in the ICU, as well as trials of cell-based therapy for other acute illnesses.
  
  
  BACKGROUND
  
  
  
  BACKGROUND
  NCT01775774 and NCT02097641.
authors.affiliation: Departments of Nephrology and Anesthesia, University of California, San Francisco, CA, USA.
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Liu
authors.affiliation: Departments of Emergency Medicine and Critical Care Medicine, University of California, San Francisco, CA, USA.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Wilson
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
authors.forename: Hanjing
authors.initials: H
authors.lastname: Zhuo
authors.affiliation: Clinical Laboratories, Bone Marrow Center, University of California, San Francisco, CA, USA.
authors.forename: Lizette
authors.initials: L
authors.lastname: Caballero
authors.affiliation: Clinical Laboratories, Bone Marrow Center, University of California, San Francisco, CA, USA.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: McMillan
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Fang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Cosgrove
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Calfee
authors.affiliation: Department of Anesthesia, University of California, San Francisco, CA, USA.
authors.forename: Jae-Woo
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Division of Hospital Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Kirsten N
authors.initials: KN
authors.lastname: Kangelaris
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gotts
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Rogers
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Levitt
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard University, Cambridge, MA, USA.
authors.forename: Jeanine P
authors.initials: JP
authors.lastname: Wiener-Kronish
authors.affiliation: Department of Psychiatry, University of California, San Francisco, CA, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Delucchi
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Leavitt
authors.affiliation: Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: McKenna
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
authors.affiliation: Departments of Medicine and Anesthesia and the Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
keywords: Acute lung injury; Clinical trial; Mesenchymal stem/stromal cell; Pulmonary edema