Septic ShockPhase 2CISS2NCT03369275
Cellular Immunotherapy for Septic Shock
A Phase 2 study testing Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells in people with Septic Shock and Sepsis, run by Ottawa Hospital Research Institute.
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 may 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 Bone Marrow-Derived Human Mesenchymal Stem Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 114 participants
- Where
- No sites listed yet
- Study dates
- Mar 2018to Oct 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 three inclusion criteria to be eligible:
- Admission to an Intensive Care Unit AND
- Cardiovascular failure that is present within the first 24 hours of admission to the ICU and is defined by the requirement for at least 15 mcg/min of norepinephrine or at least 200 mcg/min of phenylephrine or at least 0.03 U/min of vasopressin, or a combination of norepinephrine and phenylephrine that is equivalent to the total required doses (e.g. norepinephrine 8 meq/min and phenylephrine 100 mcg/min) for at least 4 consecutive hours. Participants must still require vasopressor(s) at the time of MSC infusion to be eligible. AND
- At least 1 additional organ failure, or organ hypoperfusion, as defined by the modified Multiple Organ Dysfunction Score (MODS). Criteria for organ dysfunction or organ hypoperfusion must be met within the first 24 hours of ICU admission. These include:
- Respiratory failure: mechanically ventilated with a positive end expiratory pressure (PEEP) of at least 5 cm H20, and a partial pressure of oxygen/fractional inspired oxygen concentration (P/F ratio) less than or equal to 200 on 2 separate occasions.
- Hematological failure: platelet count of less than or equal to 100 X 109 /L that has decreased by at least 50 x 109/L.
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- Acute renal failure: acute renal insufficiency with a creatinine of greater than 200 umol/L that has increased by at least 50 umol/L, or the requirement for continuous renal replacement therapy, or for participants with known chronic renal failure but not on dialysis, a 50% increase in their baseline creatinine concentration.
- Organ hypoperfusion: a lactate of at least 4 mmol/L
- Acute organ failures that meet eligibility criteria cannot have been present for more than 48 hours prior to admission to the ICU.
Who cannot join
- Another form of shock (cardiogenic, hypovolemic, obstructive) that is considered by the treating critical care staff physician as the dominant cause of shock.
- History of known chronic pulmonary hypertension with a WHO functional class of III or IV
- History of severe chronic pulmonary disease requiring home oxygen
- History of chronic severe cardiac disease including congestive heart failure or valvular dysfunction with a New York Heart Association Functional Class of III or IV, or severe ischemic heart disease with a Canadian Cardiovascular Society angina class score of III or IV.
- History of severe chronic liver disease (Child class C)
- Malignancy in the previous year (excluding resolved non-melanoma skin cancer). Participants will be excluded from the CISS2 trial if they have received any surgery, chemotherapy, or radiation for a malignancy in the previous 12 months.
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- Chronic immune suppression (chronic steroid use or chemotherapy)
- Pregnant or lactating
- Enrolment in another interventional study
- Treating physicians' impression is that the participant is moribund and that death is imminent within the subsequent 12 hours of meeting eligibility criteria
- Family, participant, or physician not committed to aggressive care. Any limitation of care will exclude the patient from enrolment in the CISS2 trial (ex: no intubation, no use of vasopressor agent(s), no renal support therapy).
- Less than 18 years of age
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Cellular Immunotherapy for Septic Shock (CISS2) A 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 may 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 mesenchymal stem cells (MSCs) in patients with septic shock. The Cellular Immunotherapy for Septic Shock (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 (CISS2) at several Canadian academic centres which will evaluate safety, signals for clinical efficacy, and continue to examine potential mechanisms of action and biological effects of MSCs in septic shock.
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 Cellular Immunotherapy for Septic Shock RCT (CISS2) will continue to evaluate safety, assess if there are signals for clinical efficacy and determine mechanisms of action and biological effects of MSCs in septic shock. To answer these aims, CISS2 will randomize 114 patients who are admitted to the ICU with septic shock to 300 million cryopreserved, allogeneic, bone marrow derived MSCs or placebo across 10 Canadian centres over approximately 2 years.
- Conditions
- Septic Shock, Sepsis, Pathologic Processes, Shock, Infection, Systemic Inflammatory Response Syndrome
- Being tested
- Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells, Placebo
- Keywords
- Mesenchymal Stem Cells, Mesenchymal Stromal Cells, Randomized Controlled Trial, Cryopreserved, Allogeneic, Phase II
- Medical subject headings
- Shock, Septic, Sepsis, Pathologic Processes, Shock, Infections, Systemic Inflammatory Response Syndrome, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic Bone Marrow-Derived Human Mesenchymal Stem CellsBiological
Cryopreserved Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.
PlaceboOther
Placebo, with excipients, will be administered intravenously.
| Study group | Role | What they receive |
|---|---|---|
| Mesenchymal Stromal Cells (MSCs) | Experimental | Intravenous infusion of 300 million Allogeneic, Bone Marrow-Derived Human Mesenchymal Stromal Cells Receives: Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem 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.
The reduction in days on mechanical ventilation, or renal replacement therapy, or vasopressors.
The number of days free from each of these support measures.
Measured: Through to 28 days post-randomization
Incidence of treatment-emergent adverse events (Safety and tolerability)
Measured: Through to 28 days post-randomization
Secondary outcomes (9)
Biological endpoints as markers of vascular permeability
Marker of vascular permeability (ex: Ang1 and 2), acute renal injury (ex: Urine TIMP2-IGFBP7, IL-18), muscle weakness (ex: micro RNA (miRNA) growth Differentiation Factor-15 and miR-181a)), mechanisms related to pathogen clearance (ex: cathelicidin, LL-37), and pro and anti-inflammatory cytokines (ex: IL-6, IL-8, IL-10, IL-1B and IL1-RA) related to potential MSC biological effects
Measured: At baseline, 1, 2, 3 and 7 days post-randomization
Mortality
All-cause mortality
Measured: Through to 12 months post-randomization
Organ Failure Scores
Sequential Organ Failure Assessment (SOFA) Score
Measured: Through to 90 days post-randomization
Organ Support Measures
Duration of mechanical ventilation and/or vasopressor agents and/or dialysis/renal replacement therapy
Measured: Through to 90 days post-randomization
Length of ICU Stay (in days)
Time in ICU
Measured: Number of elapsed days from admission until ICU discharge, up to one year
Length of Hospital Stay (in days)
Time in Hospital
Measured: Number of elapsed days from admission until hospital discharge, up to one year
Hospital Re-Admissions
Measured: At 28 days, 3 and 12 months post-randomization
Patient Reported Outcomes-FIM
Functional Independence Measure (FIM)
Measured: 7 days and 6 months post-ICU discharge
Patient Reported Outcomes-SF 36
SF-36 Score
Measured: 7 days and 6 months post-ICU discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2017
- Study startMar 2018 (estimated)
- Primary completionFeb 2020 (estimated)
- Study completionOct 2020 (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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 114 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Ontario Institute for Regenerative Medicine, Stem Cell Network
- Responsible party
- Sponsor
- Investigators
- Lauralyn McIntyre, MD, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03369275
- Sponsor's protocol ID
- 201706
- Acronym
- CISS2
- Status last verified
- Dec 2017
- First submitted
- 28 Aug 2017
- Last updated
- 11 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cellular Immunotherapy for Septic Shock (CISS2) A Phase II Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03369275
- Acronym / sponsor ID
- CISS2 / 201706
- Conditions
- Septic Shock, Sepsis, Pathologic Processes, Shock, Infection, Systemic Inflammatory Response Syndrome
- Keywords
- Mesenchymal Stem Cells, Mesenchymal Stromal Cells, Randomized Controlled Trial, Cryopreserved, Allogeneic, Phase II
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 114 participants (estimated)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Ontario Institute for Regenerative Medicine, Stem Cell Network
- Study start
- Mar 2018 (estimated)
- Primary completion
- Feb 2020 (estimated)
- Study completion
- Oct 2020 (estimated)
- First posted
- 11 Dec 2017 (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 may 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 mesenchymal stem cells (MSCs) in patients with septic shock. The Cellular Immunotherapy for Septic Shock (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 (CISS2) at several Canadian academic centres which will evaluate safety, signals for clinical efficacy, and continue to examine potential mechanisms of action and biological effects of MSCs in septic shock.
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 Cellular Immunotherapy for Septic Shock RCT (CISS2) will continue to evaluate safety, assess if there are signals for clinical efficacy and determine mechanisms of action and biological effects of MSCs in septic shock. To answer these aims, CISS2 will randomize 114 patients who are admitted to the ICU with septic shock to 300 million cryopreserved, allogeneic, bone marrow derived MSCs or placebo across 10 Canadian centres over approximately 2 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
| Arm | Type | Receives |
|---|---|---|
| Mesenchymal Stromal Cells (MSCs) | Experimental | Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem CellsIntravenous infusion of 300 million Allogeneic, Bone Marrow-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 (9 listed)
- Admission to an Intensive Care Unit AND
- Cardiovascular failure that is present within the first 24 hours of admission to the ICU and is defined by the requirement for at least 15 mcg/min of norepinephrine or at least 200 mcg/min of phenylephrine or at least 0.03 U/min of vasopressin, or a combination of norepinephrine and phenylephrine that is equivalent to the total required doses (e.g. norepinephrine 8 meq/min and phenylephrine 100 mcg/min) for at least 4 consecutive hours. Participants must still require vasopressor(s) at the time of MSC infusion to be eligible. AND
- At least 1 additional organ failure, or organ hypoperfusion, as defined by the modified Multiple Organ Dysfunction Score (MODS). Criteria for organ dysfunction or organ hypoperfusion must be met within the first 24 hours of ICU admission. These include:
- Acute organ failures that meet eligibility criteria cannot have been present for more than 48 hours prior to admission to the ICU.
Key exclusion criteria (12 listed)
- Another form of shock (cardiogenic, hypovolemic, obstructive) that is considered by the treating critical care staff physician as the dominant cause of shock.
- History of known chronic pulmonary hypertension with a WHO functional class of III or IV
- History of severe chronic pulmonary disease requiring home oxygen
- History of chronic severe cardiac disease including congestive heart failure or valvular dysfunction with a New York Heart Association Functional Class of III or IV, or severe ischemic heart disease with a Canadian Cardiovascular Society angina class score of III or IV.
- History of severe chronic liver disease (Child class C)
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 Bone Marrow-Derived Human Mesenchymal Stem CellsCryopreserved Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously. | Biological | Mesenchymal Stromal Cells (MSCs) |
| PlaceboPlacebo, with excipients, will be administered intravenously. | Other | Placebo |
Primary outcome
The reduction in days on mechanical ventilation, or renal replacement therapy, or vasopressors.
Time frame: Through to 28 days post-randomization
The number of days free from each of these support measures.
Incidence of treatment-emergent adverse events (Safety and tolerability)
Time frame: Through to 28 days post-randomization
9 secondary outcomes
Biological endpoints as markers of vascular permeability
Time frame: At baseline, 1, 2, 3 and 7 days post-randomization
Mortality
Time frame: Through to 12 months post-randomization
Organ Failure Scores
Time frame: Through to 90 days post-randomization
Organ Support Measures
Time frame: Through to 90 days post-randomization
Length of ICU Stay (in days)
Time frame: Number of elapsed days from admission until ICU discharge, up to one year
Length of Hospital Stay (in days)
Time frame: Number of elapsed days from admission until hospital discharge, up to one year
Hospital Re-Admissions
Time frame: At 28 days, 3 and 12 months post-randomization
Patient Reported Outcomes-FIM
Time frame: 7 days and 6 months post-ICU discharge
Patient Reported Outcomes-SF 36
Time frame: 7 days and 6 months post-ICU discharge
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2017.
- Individual participant dataSharing planned: Undecided
Related trials for Septic Shock
Not yet recruitingObservational study
Serum GDF-15 and LGALS3BP as Prognostic Biomarkers in Sepsis
Sepsis, Septic Shock
RecruitingPhase 3
A Trial of Adjunctive Fludrocortisone (50mcg, 100mcg or Placebo) in Critically Ill Patients With Septic Shock Receiving Hydrocortisone, Evaluating Survival and Functional Recovery and the Influence of Transcriptomic Response
Septic Shock
Recruiting
Veno-arterial Carbon Dioxide Partial Pressure Difference (CO2gap) for Early Resuscitation of Septic Shock
Sepsis - to Reduce Mortality in the Intensive Care Unit, Septic Shock
Not yet recruiting
Hemodynamic Resuscitation Guided by Non-Invasive Mean Systemic Filling Pressure to Prevent Acute Kidney Injury in Septic Shock
Acute Kidney Injury Due to Sepsis
RecruitingObservational study
Clinical Value of EMR3 in Sepsis Diagnosis, Monitoring, and Prognosis: A Multicenter Prospective Observational Study
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. This study is not recruiting at the moment.
Lauralyn McIntyre, MD principal investigator
Ottawa Hospital Research Institute
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells in people with Septic Shock and Sepsis, run by Ottawa Hospital Research Institute.
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 9 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 11 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Josee Champagne (613-737-8899 ext. 73836, jochampagne@ohri.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The reduction in days on mechanical ventilation, or renal replacement therapy, or vasopressors. (time frame: Through to 28 days post-randomization). The study lists 2 primary outcomes in all. 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 11 Dec 2017.