Liu, Kathleen DWilson, Jennifer GZhuo, HanjingCaballero, LizetteMcMillan, Melanie LFang, XiaohuiCosgrove, KatherineCalfee, Carolyn SLee, Jae-WooKangelaris, Kirsten NGotts, Jeffrey ERogers, Angela JLevitt, Joseph EWiener-Kronish, JeanineDelucchi, Kevin LLeavitt, Andrew DMcKenna, David HThompson, B TaylorMatthay, Michael A2015-02-022014Liu, K. D., J. G. Wilson, H. Zhuo, L. Caballero, M. L. McMillan, X. Fang, K. Cosgrove, et al. 2014. “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.” Annals of Intensive Care 4 (1): 22. doi:10.1186/s13613-014-0022-z. http://dx.doi.org/10.1186/s13613-014-0022-z.2110-5820http://nrs.harvard.edu/urn-3:HUL.InstRepos:13890771Background: 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. Trial registration Clinical Trials Registration: NCT01775774 and NCT02097641.en-USAcute lung injuryClinical trialMesenchymal stem/stromal cellPulmonary edemaJournal Article2015-02-0210.1186/s13613-014-0022-z