Umbilical Mesenchymal Stromal Cells as Cellular Immunotherapy for Septic Shock

NCT05969275 | Recruiting Phase 2 DMC

• 1 other identifier: UC-CISSII
• Study Type: interventional
• Target: 296
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

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

Keywords

Mesenchymal Stem Cells; Mesenchymal Stromal Cells; Randomized Controlled Trial; Cryopreserved; Allogeneic; Umbilical Cord; Phase II; Sepsis; Septic Shock

Outcome Measures

Primary Outcomes (1)

• Days free from mechanical ventilation and/or vasopressors and/or renal replacement therapy

  The number of days free from each of these support measures

  Through to 28 days post-randomization

Secondary Outcomes (20)

• Biomarkers - Vascular permeability

  At baseline, 1, 3 and 7 days post-randomization

• Biomarkers - Acute kidney injury

  At baseline, 1, 3 and 7 days post-randomization

• Biomarkers - Muscle weakness

  At baseline, 1, 3 and 7 days post-randomization

• Biomarkers - Pathogen clearance

  At baseline, 1, 3 and 7 days post-randomization

• Biomarkers - Inflammatory mediators and cytokines

  At baseline, 1, 3 and 7 days post-randomization

Study Arms (2)

Umbilical Cord Mesenchymal Stromal Cells (UC-MSCs)

EXPERIMENTAL

Intravenous infusion of 300 million allogeneic, cryopreserved, umbilical cord-derived human mesenchymal stromal cells

Biological: Allogeneic umbilical cord-derived human mesenchymal stromal cells

Placebo

PLACEBO COMPARATOR

Intravenous infusion of placebo, with excipients

Other: Placebo

Interventions

Allogeneic umbilical cord-derived human mesenchymal stromal cells BIOLOGICAL

Intravenous infusion of 300 million allogeneic, cryopreserved, umbilical cord-derived human mesenchymal stromal cells

Umbilical Cord Mesenchymal Stromal Cells (UC-MSCs)

Placebo OTHER

Intravenous infusion of placebo, with excipients

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Stem Cell Network: collaborator
• Canadian Critical Care Trials Group: collaborator
• Technische Universität Dresden: collaborator

Study Sites (2)

The Ottawa Hospital (General Campus)

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

The Ottawa Hospital (Civic Campus)

Ottawa, Ontario, K1Y 4E9, Canada

RECRUITING

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms

Study Officials

• Lauralyn McIntyre, MD

  The Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Josee Champagne

CONTACT

613-737-8899; UCCISS@ohri.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized Controlled Trial

Study Record Dates

• First Submitted: July 12, 2023
• First Posted: August 1, 2023
• Study Start: February 14, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: December 5, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)