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

Kathleen D Liu, Jennifer G Wilson, Hanjing Zhuo, Lizette Caballero, Melanie L McMillan, Xiaohui Fang, Katherine Cosgrove, Carolyn S Calfee, Jae-Woo Lee, Kirsten N Kangelaris, Jeffrey E Gotts, Angela J Rogers, Joseph E Levitt, Jeanine P Wiener-Kronish, Kevin L Delucchi, Andrew D Leavitt, David H McKenna, B Taylor Thompson, Michael A Matthay, Kathleen D Liu, Jennifer G Wilson, Hanjing Zhuo, Lizette Caballero, Melanie L McMillan, Xiaohui Fang, Katherine Cosgrove, Carolyn S Calfee, Jae-Woo Lee, Kirsten N Kangelaris, Jeffrey E Gotts, Angela J Rogers, Joseph E Levitt, Jeanine P Wiener-Kronish, Kevin L Delucchi, Andrew D Leavitt, David H McKenna, B Taylor Thompson, Michael A Matthay

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.

Clinical trials registration: NCT01775774 and NCT02097641.

Keywords: Acute lung injury; Clinical trial; Mesenchymal stem/stromal cell; Pulmonary edema.

Figures

Figure 1
Figure 1
Flow diagram for the phase 1 component of the START trial. Abbreviations are as follows: acute respiratory distress syndrome, ARDS; adverse event, AE; bone marrow transplantation, BMT; Data Safety Monitoring Board, DSMB; positive end-expiratory pressure, PEEP.

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