Using umbilical mesenchymal stromal cells to treat septic shock

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

This study is testing whether giving umbilical stem cells can help people with septic shock recover better than a placebo.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 296 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ottawa Hospital Research Institute (Academic / other)
• Drugs / interventions: Immunotherapy
• Locations: 2 sites (Ottawa, Ontario and 1 other locations)
• Trial ID: NCT05969275 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of umbilical mesenchymal stromal cells (MSCs) as a cellular immunotherapy for patients suffering from septic shock, a severe condition characterized by organ failure due to infection. The study will randomly assign 296 patients admitted to the ICU with septic shock to receive either 300 million cryopreserved, allogeneic MSCs or a placebo. The primary focus is to evaluate intermediate measures of clinical efficacy, while secondary outcomes will include safety, biomarkers, clinical outcomes, and health economic analysis. Conducted across several Canadian academic centers, this Phase II trial builds on previous Phase I findings that indicated the safety and feasibility of MSC treatment.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older who are admitted to the ICU with septic shock and exhibit cardiovascular organ failure related to infection.

Not a fit: Patients who do not have septic shock or those who do not meet the specific organ failure criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and quality of life for patients suffering from septic shock.

How similar studies have performed: While the use of MSCs in treating septic shock is a novel approach, previous studies have shown promising results in pre-clinical models, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

A participant must meet all the following inclusion criteria at time of randomization to be eligible:

1. At least 18 years of age AND
2. Requirement for admission to the intensive care unit AND
3. Index admission to the intensive care unit AND
4. 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
5. Clinician impression that cardiovascular organ failure is related to infection AND
6. 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:

   1. 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
   2. Hematological failure: platelet count of \</= 100 X 10\^9/L OR
   3. 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
   4. 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 Criteria:

Patients will be excluded if they have at least one of the following at time of randomization:

1. Another form of shock (cardiogenic, hypovolemic, obstructive) OR
2. History of known chronic pulmonary hypertension with a WHO functional class of IV OR
3. History of severe chronic pulmonary disease requiring home oxygen OR
4. 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
5. History of severe chronic liver disease (Child-Pugh Class C or model for end stage liver disease (MELD) Score \>= 15) OR
6. Malignancy in previous 1 year (excluding resolved non-melanoma skin cancer) OR
7. Treating physician impression that death is imminent within the 12 hours after meeting eligibility criteria OR
8. Pregnant or lactating OR
9. Family or patient not committed to aggressive care

Where this trial is running

Ottawa, Ontario and 1 other locations

• The Ottawa Hospital (General Campus) — Ottawa, Ontario, Canada (Recruiting)
• The Ottawa Hospital (Civic Campus) — Ottawa, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Lauralyn McIntyre, MD — Ottawa Hospital Research Institute
• Study coordinator: Josee Champagne

Conditions Septic Shock; Sepsis; Pathologic Processes; Shock; Systemic Inflammatory Response Syndrome; Inflammation; Infections; Mesenchymal Stem Cells