Umbilical Mesenchymal Stromal Cells as Cellular Immunotherapy for Septic Shock: A Multi-Center, Double Blind, Phase II Randomized Controlled Trial
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).
∙ A participant must meet all the following inclusion criteria at time of randomization to be eligible:
• 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
• Clinician impression that cardiovascular organ failure is related to infection AND
• There is at least 1 other acute organ failure according to modified individual Sequential Organ Failure Assessment Scores within 24 hours of meeting Cardiovascular organ failure defined by:
‣ Respiratory failure: invasive or non-invasive mechanical ventilation with a positive end expiratory pressure (PEEP) \>/= 5 cm H2O and a partial pressure of oxygen/fractional inspired oxygen concentration (P/F ratio \</= 200), OR high-flow nasal canula oxygen therapy (minimum total flow rate of 30 lpm and 40% FiO2); OR
⁃ Hematological failure: platelet count of \</= 100 X 10\^9/L OR
⁃ Acute kidney injury: acute renal insufficiency with a creatinine of \>/= 200 umol/L, or the requirement for new renal replacement therapy, or for participants with known chronic renal failure but not on dialysis, a 50% increase in their baseline creatinine concentration OR
⁃ Organ hypoperfusion: a lactate \>/= 4 mmol/L
∙ Acute organ failures that meet eligibility criteria must not have been present for greater than 48 hours prior to meeting the eligibility criteria.