Septic ShockPhase 2UC-CISSIINCT05969275
Umbilical Mesenchymal Stromal Cells as Cellular Immunotherapy for Septic Shock
A Phase 2 study testing Allogeneic umbilical cord-derived human mesenchymal stromal cells in people with Septic Shock and Sepsis, run by Ottawa Hospital Research Institute at 2 sites in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Sepsis, Pathologic Processes
- What is being tested?
- Allogeneic umbilical cord-derived human mesenchymal stromal cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 296 participants
- Where
- 2 sitesCanada
- Study dates
- 14 Feb 2024to 31 Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A participant must meet all the following inclusion criteria at time of randomization to be eligible:
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites, 2 recruiting
- Recruiting
The Ottawa Hospital (General Campus)
Ottawa, Ontario, K1H 8L6
Irene Watpool, RN, UCCISS@ohri.ca
Lauralyn McIntyre, MD
- Recruiting
The Ottawa Hospital (Civic Campus)
Ottawa, Ontario, K1Y 4E9
Rebecca Porteous, RN, UCCISS@ohri.ca
Lauralyn McIntyre, MD
About this study
Official title: Umbilical Mesenchymal Stromal Cells as Cellular Immunotherapy for Septic Shock: A Multi-Center, Double Blind, Phase II Randomized Controlled Trial
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).
Read the 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
- Being tested
- Allogeneic umbilical cord-derived human mesenchymal stromal cells, Placebo
- Keywords
- Mesenchymal Stem Cells, Mesenchymal Stromal Cells, Randomized Controlled Trial, Cryopreserved, Allogeneic, Umbilical Cord, Phase II, Sepsis, Septic Shock
- Medical subject headings
- Shock, Septic, Sepsis, Pathologic Processes, Shock, Systemic Inflammatory Response Syndrome, Inflammation, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic umbilical cord-derived human mesenchymal stromal cellsBiological
Intravenous infusion of 300 million allogeneic, cryopreserved, umbilical cord-derived human mesenchymal stromal cells
PlaceboOther
Intravenous infusion of placebo, with excipients
| Study group | Role | What they receive |
|---|---|---|
| Umbilical Cord Mesenchymal Stromal Cells (UC-MSCs) | Experimental | Intravenous infusion of 300 million allogeneic, cryopreserved, umbilical cord-derived human mesenchymal stromal cells Receives: Biological: Allogeneic umbilical cord-derived human mesenchymal stromal cells |
| Placebo | Placebo comparator | Intravenous infusion of placebo, with excipients Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days free from mechanical ventilation and/or vasopressors and/or renal replacement therapy
The number of days free from each of these support measures
Measured: Through to 28 days post-randomization
Secondary outcomes (20)
Biomarkers - Vascular permeability
Markers of vascular permeability (ex: Angpt1 and 2)
Measured: At baseline, 1, 3 and 7 days post-randomization
Biomarkers - Acute kidney injury
Markers of acute kidney injury (ex: Urine TIMP2-IGFBP7, IL-18)
Measured: At baseline, 1, 3 and 7 days post-randomization
Biomarkers - Muscle weakness
Markers of muscle weakness (ex: micro RNA [miR] miR-181a, growth differentiation Factor-15)
Measured: At baseline, 1, 3 and 7 days post-randomization
Biomarkers - Pathogen clearance
Mechanisms related to pathogen clearance (ex: cathelicidin, LL-37)
Measured: At baseline, 1, 3 and 7 days post-randomization
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)
Measured: At baseline, 1, 3 and 7 days post-randomization
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
Measured: Through to 7 days post-randomization
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
Measured: Through to 28 days post-randomization
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)
Measured: Through to 28 days post-randomization
Mortality
All-cause mortality
Measured: 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
Length of ICU Stay (in days)
Time in ICU
Measured: Number of elapsed days from admission until ICU discharge, up to 1 year
Length of Hospital Stay (in days)
Time in hospital
Measured: Number of elapsed days from admission until hospital discharge, up to 1 year
Hospital Re-Admissions
Re-admission to any hospital
Measured: At 28 days, 90 days and 1 year post-randomization
ICU Re-Admissions
Re-admission to ICU during study hospital admission
Measured: During index study hospital admission (through study completion, up to 1 year)
Organ Failure Rates
Organ failure rates (using Sequential Organ Failure Assessment Score), described individually and in composite
Measured: Through to 90 days post-randomization
Days free from mechanical ventilation
Number of days free from mechanical ventilation
Measured: Through to 90 days post-randomization
Days free from vasopressors
Number of days free from vasopressor agents
Measured: Through to 90 days post-randomization
Days free from renal replacement therapy
Number of days free from renal replacement therapy
Measured: Through to 90 days post-randomization
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)
Measured: At 30 days, 6 months and 1 year post-randomization
Patient Reported Outcomes - Short Form Survey-36 (SF-36)
SF-36 scores ranging from 0 to 100 (with higher scores indicating better health status)
Measured: At 30 days, 6 months and 1 year post-randomization
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
Measured: Through to 28 days post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2023
- Study start14 Feb 2024
- Primary completion30 Sep 2026 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized Controlled Trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 296 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Stem Cell Network, Canadian Critical Care Trials Group, Technische Universität Dresden
- Responsible party
- Sponsor
- Investigators
- Lauralyn McIntyre, MD, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05969275
- Sponsor's protocol ID
- UC-CISSII
- Acronym
- UC-CISSII
- Status last verified
- Dec 2024
- First submitted
- 12 Jul 2023
- Last updated
- 5 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Umbilical Mesenchymal Stromal Cells as Cellular Immunotherapy for Septic Shock: A Multi-Center, Double Blind, Phase II Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05969275
- Acronym / sponsor ID
- UC-CISSII / UC-CISSII
- Conditions
- Septic Shock, Sepsis, Pathologic Processes, Shock, Systemic Inflammatory Response Syndrome, Inflammation
- Keywords
- Mesenchymal Stem Cells, Mesenchymal Stromal Cells, Randomized Controlled Trial, Cryopreserved, Allogeneic, Umbilical Cord, Phase II, Sepsis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 296 participants (estimated)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Stem Cell Network, Canadian Critical Care Trials Group, Technische Universität Dresden
- Study start
- 14 Feb 2024 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 1 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized Controlled Trial
| Arm | Type | Receives |
|---|---|---|
| Umbilical Cord Mesenchymal Stromal Cells (UC-MSCs) | Experimental | Biological: Allogeneic umbilical cord-derived human mesenchymal stromal cellsIntravenous infusion of 300 million allogeneic, cryopreserved, umbilical cord-derived human mesenchymal stromal cells |
| Placebo | Placebo comparator | Other: PlaceboIntravenous infusion of placebo, with excipients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- A participant must meet all the following inclusion criteria at time of randomization to be eligible:
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogeneic umbilical cord-derived human mesenchymal stromal cellsIntravenous infusion of 300 million allogeneic, cryopreserved, umbilical cord-derived human mesenchymal stromal cells | Biological | Umbilical Cord Mesenchymal Stromal Cells (UC-MSCs) |
| PlaceboIntravenous infusion of placebo, with excipients | Other | Placebo |
Primary outcome
Days free from mechanical ventilation and/or vasopressors and/or renal replacement therapy
Time frame: Through to 28 days post-randomization
The number of days free from each of these support measures
20 secondary outcomes
Biomarkers - Vascular permeability
Time frame: At baseline, 1, 3 and 7 days post-randomization
Biomarkers - Acute kidney injury
Time frame: At baseline, 1, 3 and 7 days post-randomization
Biomarkers - Muscle weakness
Time frame: At baseline, 1, 3 and 7 days post-randomization
Biomarkers - Pathogen clearance
Time frame: At baseline, 1, 3 and 7 days post-randomization
Biomarkers - Inflammatory mediators and cytokines
Time frame: At baseline, 1, 3 and 7 days post-randomization
Safety - Adverse Event
Time frame: Through to 7 days post-randomization
Safety - Serious and Unexpected Adverse Events
Time frame: Through to 28 days post-randomization
Safety - Expected Adverse Events
Time frame: Through to 28 days post-randomization
Mortality
Time frame: 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
Length of ICU Stay (in days)
Time frame: Number of elapsed days from admission until ICU discharge, up to 1 year
Length of Hospital Stay (in days)
Time frame: Number of elapsed days from admission until hospital discharge, up to 1 year
Hospital Re-Admissions
Time frame: At 28 days, 90 days and 1 year post-randomization
ICU Re-Admissions
Time frame: During index study hospital admission (through study completion, up to 1 year)
Organ Failure Rates
Time frame: Through to 90 days post-randomization
Days free from mechanical ventilation
Time frame: Through to 90 days post-randomization
Days free from vasopressors
Time frame: Through to 90 days post-randomization
Days free from renal replacement therapy
Time frame: Through to 90 days post-randomization
Patient Reported Outcomes - Functional Independence Measure (FIM)
Time frame: At 30 days, 6 months and 1 year post-randomization
Patient Reported Outcomes - Short Form Survey-36 (SF-36)
Time frame: At 30 days, 6 months and 1 year post-randomization
Health Economic Analysis
Time frame: Through to 28 days post-randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2024.
- Individual participant dataSharing planned: No
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Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lauralyn McIntyre, MD principal investigator
Ottawa Hospital Research Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Allogeneic umbilical cord-derived human mesenchymal stromal cells in people with Septic Shock and Sepsis, run by Ottawa Hospital Research Institute at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Josee Champagne (613-737-8899 ext. 73836, UCCISS@ohri.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Days free from mechanical ventilation and/or vasopressors and/or renal replacement therapy (time frame: Through to 28 days post-randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2024.