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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 Liu1*, Jennifer G Wilson2, Hanjing Zhuo3, Lizette Caballero4, Melanie L McMillan4, Xiaohui Fang3, Katherine Cosgrove5, Carolyn S Calfee6, Jae-Woo Lee7, Kirsten N Kangelaris8, Jeffrey E Gotts6, Angela J Rogers9, Joseph E Levitt9, Jeanine P Wiener-Kronish10, Kevin L Delucchi11, Andrew D Leavitt12, David H McKenna13, B Taylor Thompson5 and Michael A Matthay14

Author Affiliations

1 Departments of Nephrology and Anesthesia, University of California, San Francisco, CA, USA

2 Departments of Emergency Medicine and Critical Care Medicine, University of California, San Francisco, CA, USA

3 Cardiovascular Research Institute, University of California, San Francisco, CA, USA

4 Clinical Laboratories, Bone Marrow Center, University of California, San Francisco, CA, USA

5 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

6 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, CA, USA

7 Department of Anesthesia, University of California, San Francisco, CA, USA

8 Division of Hospital Medicine, Department of Medicine, University of California, San Francisco, CA, USA

9 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USA

10 Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard University, Cambridge, MA, USA

11 Department of Psychiatry, University of California, San Francisco, CA, USA

12 Department of Laboratory Medicine, University of California, San Francisco, CA, USA

13 Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

14 Departments of Medicine and Anesthesia and the Cardiovascular Research Institute, University of California, San Francisco, CA, USA

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Annals of Intensive Care 2014, 4:22  doi:10.1186/s13613-014-0022-z

Published: 3 July 2014

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.

Trial registration

Clinical Trials Registration: NCT01775774 webcite and NCT02097641 webcite.

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