Septic shock is associated with substantial burden in terms of both mortality and morbidity for survivors of this illness. Pre-clinical sepsis studies suggest that mesenchymal stem (stromal) cells (MSCs) modulate inflammation, enhance pathogen clearance and tissue repair and reduce death. Our team has completed a Phase I dose escalation and safety clinical trial that evaluated MSCs in patients with septic shock. The Cellular Immunotherapy for Septic Shock Phase I (CISS) trial established that MSCs appear safe and that a randomized controlled trial (RCT) is feasible. Based on these data, the investigators have planned a phase II RCT (UC-CISS II) at several Canadian academic centres which will evaluate intermediate measures of clinical efficacy (primary outcome), as well as biomarkers, safety, clinical outcome measures, and a health economic analysis (secondary outcomes).
At least 18 years of age AND
Requirement for admission to the intensive care unit AND
Index admission to the intensive care unit AND
Cardiovascular organ failure for at least 1 consecutive hour defined by the requirement of at least 5 mcg/min of norepinephrine or 100 mcg/min of phenylephrine or 0.03 U/min vasopressin AND
Another form of shock (cardiogenic, hypovolemic, obstructive) OR
History of known chronic pulmonary hypertension with a WHO functional class of IV OR
History of severe chronic pulmonary disease requiring home oxygen OR
History of severe chronic cardiac disease including congestive heart failure or valvular dysfunction with a New York Heart Association Functional class IV or severe chronic ischemic heart disease with a Canadian Cardiovascular Society angina class score IV OR
Parallel
Allogeneic umbilical cord-derived human mesenchymal stromal cells
Biological/VaccineIntravenous infusion of 300 million allogeneic, cryopreserved, umbilical cord-derived human mesenchymal stromal cells
Placebo
Other interventionIntravenous infusion of placebo, with excipients
Days free from mechanical ventilation and/or vasopressors and/or renal replacement therapy
The number of days free from each of these support measures
Biomarkers - Vascular permeability
Markers of vascular permeability (ex: Angpt1 and 2)
Biomarkers - Acute kidney injury
Markers of acute kidney injury (ex: Urine TIMP2-IGFBP7, IL-18)
Biomarkers - Muscle weakness
Markers of muscle weakness (ex: micro RNA \[miR\] miR-181a, growth differentiation Factor-15)
Biomarkers - Pathogen clearance
Mechanisms related to pathogen clearance (ex: cathelicidin, LL-37)
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Ottawa Hospital Research Institute
Lead sponsor
Canadian Institutes of Health Research (CIHR)
Collaborator
Stem Cell Network
Collaborator
Canadian Critical Care Trials Group
Collaborator
Technische Universität Dresden
Collaborator
