RecruitingPhase 2NCT05969275

Umbilical Mesenchymal Stromal Cells as Cellular Immunotherapy for Septic Shock

Umbilical Mesenchymal Stromal Cells as Cellular Immunotherapy for Septic Shock: A Multi-Center, Double Blind, Phase II Randomized Controlled Trial

Sponsor

Ottawa Hospital Research Institute

Enrollment

296 participants

Start Date

Feb 14, 2024

Study Type

INTERVENTIONAL

Conditions

Sepsis Pathologic Processes Infections Systemic Inflammatory Response Syndrome Inflammation Septic Shock Shock

Summary

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).

Eligibility

Min Age: 18 Years

Inclusion Criteria11

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.

Exclusion Criteria10

Patients will be excluded if they have at least one of the following at time of randomization:
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
History of severe chronic liver disease (Child-Pugh Class C or model for end stage liver disease (MELD) Score >= 15) OR
Malignancy in previous 1 year (excluding resolved non-melanoma skin cancer) OR
Treating physician impression that death is imminent within the 12 hours after meeting eligibility criteria OR
Pregnant or lactating OR
Family or patient not committed to aggressive care