Umbilical Mesenchymal Stromal Cells as Cellular Immunotherapy for Septic Shock

NCT ID: NCT05969275

Last Updated: 2024-12-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 296 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-14
• Study Completion Date: 2027-03-31

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).

Detailed Description

Septic shock is a devastating illness and the most severe form of infection seen in the intensive care unit (ICU). It is characterized by cardiovascular collapse, failure of organs and is common with severe repercussions including a mortality of 20-40%. Survivors suffer long-term impairment in function and reduced quality of life (QOL). Despite decades of research examining different immune therapies, none has proven successful and supportive care remains the mainstay of therapy, at a cost of approximately 4-billion dollars in Canada annually. MSCs represent a potentially novel treatment for sepsis because in animal models, MSCs have been shown to modulate the immune system, increase pathogen clearance, restore organ function, and reduce death.

The Phase II multi-centre double blind Umbilical Cord Cellular Immunotherapy for Septic Shock RCT (UC-CISS II) will examine intermediate measures of clinical efficacy (primary outcome) as well as biomarkers, safety, clinical outcome measures, and a health economic analysis (secondary outcomes). To answer these aims, UC-CISS II will randomize 296 patients who are admitted to the ICU with septic shock to 300 million cryopreserved, allogeneic, umbilical cord-derived MSCs or placebo across several Canadian academic centres over approximately 2.5 years.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Umbilical Cord Mesenchymal Stromal Cells (UC-MSCs)

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

Group Type: EXPERIMENTAL

Allogeneic umbilical cord-derived human mesenchymal stromal cells

Intervention Type: BIOLOGICAL

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

Placebo

Intravenous infusion of placebo, with excipients

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Intravenous infusion of placebo, with excipients

Interventions

Allogeneic umbilical cord-derived human mesenchymal stromal cells

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

Intervention Type: BIOLOGICAL

Placebo

Intravenous infusion of placebo, with excipients

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Stem Cell Network

OTHER

Sponsor Role: collaborator

Canadian Critical Care Trials Group

OTHER

Sponsor Role: collaborator

Technische Universität Dresden

OTHER

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lauralyn McIntyre, MD

Role: PRINCIPAL_INVESTIGATOR

The Ottawa Hospital Research Institute

Locations

The Ottawa Hospital (General Campus)

Ottawa, Ontario, Canada

Site Status: RECRUITING

The Ottawa Hospital (Civic Campus)

Ottawa, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Josee Champagne

Role: CONTACT

Phone: 613-737-8899

Email: UCCISS@ohri.ca

Facility Contacts

Irene Watpool, RN

Role: primary

Rebecca Porteous, RN

Role: primary

Other Identifiers

UC-CISSII

Identifier Type: -

Identifier Source: org_study_id