- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03369275
Cellular Immunotherapy for Septic Shock (CISS2)
Cellular Immunotherapy for Septic Shock (CISS2) A Phase II Randomized Controlled Trial
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Josee Champagne
- Phone Number: 73836 613-737-8899
- Email: jochampagne@ohri.ca
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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.
- 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.
Exclusion Criteria:
- 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.
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Mesenchymal Stromal Cells (MSCs)
Intravenous infusion of 300 million Allogeneic, Bone Marrow-Derived Human Mesenchymal Stromal Cells
|
Cryopreserved Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.
|
PLACEBO_COMPARATOR: Placebo
Intravenous infusion of Placebo, with excipients
|
Placebo, with excipients, will be administered intravenously.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Through to 28 days post-randomization
|
Incidence of treatment-emergent adverse events (Safety and tolerability)
Time Frame: Through to 28 days post-randomization
|
Through to 28 days post-randomization
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Biological endpoints as markers of vascular permeability
Time Frame: At baseline, 1, 2, 3 and 7 days post-randomization
|
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
|
At baseline, 1, 2, 3 and 7 days post-randomization
|
Mortality
Time Frame: Through to 12 months post-randomization
|
All-cause mortality
|
Through to 12 months post-randomization
|
Organ Failure Scores
Time Frame: Through to 90 days post-randomization
|
Sequential Organ Failure Assessment (SOFA) Score
|
Through to 90 days post-randomization
|
Organ Support Measures
Time Frame: Through to 90 days post-randomization
|
Duration of mechanical ventilation and/or vasopressor agents and/or dialysis/renal replacement therapy
|
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
|
Time in ICU
|
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
|
Time in Hospital
|
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
|
At 28 days, 3 and 12 months post-randomization
|
|
Patient Reported Outcomes-FIM
Time Frame: 7 days and 6 months post-ICU discharge
|
Functional Independence Measure (FIM)
|
7 days and 6 months post-ICU discharge
|
Patient Reported Outcomes-SF 36
Time Frame: 7 days and 6 months post-ICU discharge
|
SF-36 Score
|
7 days and 6 months post-ICU discharge
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Lauralyn McIntyre, MD, The Ottawa Hospital Research Institute
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 201706
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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