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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05969275
Other study ID # UC-CISSII
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date February 14, 2024
Est. completion date March 31, 2027

Study information

Verified date February 2024
Source Ottawa Hospital Research Institute
Contact Josee Champagne
Phone 613-737-8899
Email UCCISS@ohri.ca
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 296
Est. completion date March 31, 2027
Est. primary completion date September 30, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: A participant must meet all the following inclusion criteria 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, OR high-flow nasal canula oxygen therapy (minimum total flow rate of 40 lpm); and a partial pressure of oxygen/fractional inspired oxygen concentration (P/F ratio) </= 200 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 admission to the ICU. Exclusion Criteria: Patients will be excluded if they have at least one of the following: 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

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Allogeneic umbilical cord-derived human mesenchymal stromal cells
Intravenous infusion of 300 million allogeneic, cryopreserved, umbilical cord-derived human mesenchymal stromal cells
Other:
Placebo
Intravenous infusion of placebo, with excipients

Locations

Country Name City State
Canada The Ottawa Hospital (Civic Campus) Ottawa Ontario
Canada The Ottawa Hospital (General Campus) Ottawa Ontario

Sponsors (5)

Lead Sponsor Collaborator
Ottawa Hospital Research Institute Canadian Critical Care Trials Group, Canadian Institutes of Health Research (CIHR), Stem Cell Network, Technische Universität Dresden

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Biomarkers - Vascular permeability Markers of vascular permeability (ex: Angpt1 and 2) At baseline, 1, 3 and 7 days post-randomization
Secondary Biomarkers - Acute kidney injury Markers of acute kidney injury (ex: Urine TIMP2-IGFBP7, IL-18) At baseline, 1, 3 and 7 days post-randomization
Secondary Biomarkers - Muscle weakness Markers of muscle weakness (ex: micro RNA [miR] miR-181a, growth differentiation Factor-15) At baseline, 1, 3 and 7 days post-randomization
Secondary Biomarkers - Pathogen clearance Mechanisms related to pathogen clearance (ex: cathelicidin, LL-37) At baseline, 1, 3 and 7 days post-randomization
Secondary Biomarkers - Inflammatory mediators and cytokines Pro- and anti-inflammatory mediators and cytokines (ex: CRP, IL-6, IL-8, IL-10, IL-1B and IL1-RA) At baseline, 1, 3 and 7 days post-randomization
Secondary Safety - Adverse Event Safety of study treatment administration, examined for the occurrence of any adverse event (which requires treatment or intervention) regardless of relationship to study treatment Through to 7 days post-randomization
Secondary Safety - Serious and Unexpected Adverse Events Safety of study treatment administration, examined for the occurrence of serious and unexpected adverse events that are considered possibly or related to the study treatment Through to 28 days post-randomization
Secondary Safety - Expected Adverse Events Safety of study treatment administration, examined for the occurrence of expected adverse events (including nosocomial infections, acute coronary syndrome, tachy and bradyarrhythmia, clinically important bleeding, ARDS and thrombotic/thromboembolic events) Through to 28 days post-randomization
Secondary Mortality All-cause mortality In ICU (through study completion, up to 1 year), in hospital (through study completion, up to 1 year), 28 days, 90 days, 6 months and 1 year post-randomization
Secondary Length of ICU Stay (in days) Time in ICU Number of elapsed days from admission until ICU discharge, up to 1 year
Secondary Length of Hospital Stay (in days) Time in hospital Number of elapsed days from admission until hospital discharge, up to 1 year
Secondary Hospital Re-Admissions Re-admission to any hospital At 28 days, 90 days and 1 year post-randomization
Secondary ICU Re-Admissions Re-admission to ICU during study hospital admission During index study hospital admission (through study completion, up to 1 year)
Secondary Organ Failure Rates Organ failure rates (using Sequential Organ Failure Assessment Score), described individually and in composite Through to 90 days post-randomization
Secondary Days free from mechanical ventilation Number of days free from mechanical ventilation Through to 90 days post-randomization
Secondary Days free from vasopressors Number of days free from vasopressor agents Through to 90 days post-randomization
Secondary Days free from renal replacement therapy Number of days free from renal replacement therapy Through to 90 days post-randomization
Secondary Patient Reported Outcomes - Functional Independence Measure (FIM) FIM scores ranging from 18 to 126 (where the higher the score, the more independent the patient is) At 30 days, 6 months and 1 year post-randomization
Secondary Patient Reported Outcomes - Short Form Survey-36 (SF-36) SF-36 scores ranging from 0 to 100 (with higher scores indicating better health status) At 30 days, 6 months and 1 year post-randomization
Secondary Health Economic Analysis A cost-utility analysis of MSCs compared to placebo from a perspective of Canada's publicly funded health care system will be conducted Through to 28 days post-randomization
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