Grant: Operating Grant: Clinical Trials Projects - Indirect Costs

Severe infection with shock (septic shock) in the intensive care unit (ICU) accounts for approximately 20% of admissions, of which 20 to 40% will die. Septic shock is associated with an uncontrolled inflammatory response that is initiated by an infectious organism. Studies done in septic animals suggest that the infusion of mesenchymal stem cells (MSCs) balance inflammation, help with repair of injured organs, and reduce death. Hence, it represents a promising potential therapy for septic shock. We completed the first in the World Phase I safety trial of MSCs (n=9) versus controls (n=21) in 30 patients with septic shock (CISS Phase I trial). The CISS Phase I trial results confirmed the optimum dose and that treatment with MSCs is safe. The primary objective of the Phase II trial (UC-CISS II) will determine whether MSCs reduce the amount of time that patients spend on organ support measures; these include mechanical ventilation, intravenous vasoactive medications, and kidney replacement therapy. UC-CISS II will randomize 296 ICU patients with septic shock to previously frozen MSCs or placebo across 15 Canadian centres. The frequency of adverse events (AEs) and serious AEs will be recorded. Blood will be drawn for inflammation markers and the effectiveness of MSC therapy as compared to its cost will be evaluated. If any one of the organ support measures are superior to placebo, the UC-CISS II team will proceed to a larger, international Phase III MSC trial which if positive could save thousands of lives and restore the function and quality of life of septic shock survivors.