Septic ShockPhase 1CISSNCT02421484
Cellular Immunotherapy for Septic Shock: A Phase I Trial
A Phase 1 study testing Allogeneic mesenchymal stromal cells in people with Septic Shock, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial summary
This is a Phase I open label dose escalation trial of human allogeneic bone marrow derived mesenchymal stromal cells (MSCs) for the treatment of septic shock. The main purpose of the study is to assess the safety of MSCs in patients with septic shock. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Allogeneic mesenchymal stromal cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteCanada
- Study dates
- May 2015to 30 Oct 2018
- Phase
- Phase 1
- 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 5 inclusion criteria to be eligible:
- Admission to the Ottawa Hospital Intensive Care Unit
- Receipt of appropriate broad spectrum antibiotics for the suspected/confirmed infectious source and adequate source control according to the opinion of the treating critical care physician
- Within 24 hours of admission to the ICU, receipt of reasonable levels of fluid administration and resuscitation as indicated by:
- a central venous pressure of at least 8 mm Hg AND
- a central venous oxygen saturation of at least 70%.
- Cardiovascular failure that is present within the first 24 hours of admission to the ICU and that is present for at least 4 consecutive hours AND
- Deterioration or lack of improvement in at least 1 additional organ function, 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
Who cannot join
- Another form of shock (cardiogenic, hypovolemic, obstructive) that is considered by the treating critical care physician as the dominant cause of shock
- History of known pulmonary hypertension with a WHO functional class of III or IV
- History of severe pulmonary disease requiring home oxygen
- History of severe cardiac disease 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 liver disease (Child class C)
- Malignancy in the previous 2 years (excluding resolved non-melanoma skin cancer).
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- Chronic immune suppression
- History of anaphylaxis
- Pregnant or lactating
- Enrolment in another interventional study
- Family, participant, or physician not committed to aggressive care
- Less than 18 years of age
Trial locations and contacts
1 site in 1 country.
About this study
This is a Phase I open label dose escalation trial of human allogeneic bone marrow derived mesenchymal stromal cells (MSCs) for the treatment of septic shock. The main purpose of the study is to assess the safety of MSCs in patients with septic shock.
Read the detailed description
Septic shock is one of the most common and devastating health problems in the intensive care unit, with a mortality rate of approximately 40% and a staggering economic burden of approximately 4 billion dollars annually in Canada. Mesenchymal stromal cells (MSCs) may provide a promising new treatment avenue, as pre-clinical research has shown that these cells can modify a number of pathophysiological processes that are central to sepsis and greatly reduce rates of organ failure and death. This dramatic effect appears to be due to the ability of MSCs to modify the inflammatory cascade, augment tissue repair and enhance pathogen clearance. MSCs have been evaluated in randomized clinical trials including those with myocardial infarction, heart failure, neurological and metabolic disorders, hematological malignancies, and chronic obstructive pulmonary disease with no serious safety concerns. However, MSC therapy has not yet been evaluated in humans with septic shock. Prior to a randomized controlled trial to examine the efficacy of MSCs in septic shock, an evaluation of safety is necessary. The Cellular Immunotherapy for Septic Shock (CISS) trial is an open label Phase I dose escalation trial that will evaluate the safety of MSC therapy in this vulnerable population.
- Conditions
- Septic Shock
- Being tested
- Allogeneic mesenchymal stromal cells
- Keywords
- Phase I clinical trial, stem cell, mesenchymal stromal cell, mesenchymal stem cell
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic mesenchymal stromal cellsBiological
The allogeneic mesenchymal stromal cells will be administered intravenously.
| Study group | Role | What they receive |
|---|---|---|
| allogeneic mesenchymal stromal cells | Experimental | This is a Phase 1 dose escalation clinical trial that constitutes 3 dose cohorts with 3 participants per cohort who will receive intravenous doses of allogeneic bone marrow derived allogeneic mesenchymal stromal cells--0.3 million cells/kg, 1.0 million cells/kg, and 3.0 million cells/kg. We will proceed from the lower dose to the next higher dose if there are no safety concerns for each cohort. Receives: Biological: Allogeneic mesenchymal stromal cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events as a measure of safety and tolerability
A historical cohort that met CISS eligibility criteria were previously enrolled to compare the incidence of adverse events with the CISS interventional arm.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2015 (estimated)
- Study startMay 2015
- Primary completionJun 2016
- Study completion30 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Lauralyn McIntyre, MD, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02421484
- Sponsor's protocol ID
- 2014809
- Acronym
- CISS
- Status last verified
- Oct 2018
- First submitted
- 8 Feb 2015
- Last updated
- 31 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: The sample size of the interventional arm is very small and the sharing of individual data has privacy and confidentiality implications.
Publications
McIntyre LA, Stewart DJ, Mei SHJ, Courtman D, Watpool I, Granton J, Marshall J, Dos Santos C, Walley KR, Winston BW, Schlosser K, Fergusson DA; Canadian Critical Care Trials Group; Canadian Critical Care Translational Biology Group. Cellular Immunotherapy for Septic Shock. A Phase I Clinical Trial. Am J Respir Crit Care Med. 2018 Feb 1;197(3):337-347. doi: 10.1164/rccm.201705-1006OC.
PubMed 28960096
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cellular Immunotherapy for Septic Shock: A Phase I Trial
- ClinicalTrials.gov ID
- NCT02421484
- Acronym / sponsor ID
- CISS / 2014809
- Conditions
- Septic Shock
- Keywords
- Phase I clinical trial, stem cell, mesenchymal stromal cell, mesenchymal stem cell
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- May 2015
- Primary completion
- Jun 2016 (actual)
- Study completion
- 30 Oct 2018 (actual)
- First posted
- 20 Apr 2015 (estimated)
- 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.
This is a Phase I open label dose escalation trial of human allogeneic bone marrow derived mesenchymal stromal cells (MSCs) for the treatment of septic shock. The main purpose of the study is to assess the safety of MSCs in patients with septic shock.
Detailed description
Septic shock is one of the most common and devastating health problems in the intensive care unit, with a mortality rate of approximately 40% and a staggering economic burden of approximately 4 billion dollars annually in Canada. Mesenchymal stromal cells (MSCs) may provide a promising new treatment avenue, as pre-clinical research has shown that these cells can modify a number of pathophysiological processes that are central to sepsis and greatly reduce rates of organ failure and death. This dramatic effect appears to be due to the ability of MSCs to modify the inflammatory cascade, augment tissue repair and enhance pathogen clearance. MSCs have been evaluated in randomized clinical trials including those with myocardial infarction, heart failure, neurological and metabolic disorders, hematological malignancies, and chronic obstructive pulmonary disease with no serious safety concerns. However, MSC therapy has not yet been evaluated in humans with septic shock. Prior to a randomized controlled trial to examine the efficacy of MSCs in septic shock, an evaluation of safety is necessary. The Cellular Immunotherapy for Septic Shock (CISS) trial is an open label Phase I dose escalation trial that will evaluate the safety of MSC therapy in this vulnerable population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| allogeneic mesenchymal stromal cells | Experimental | Biological: Allogeneic mesenchymal stromal cellsThis is a Phase 1 dose escalation clinical trial that constitutes 3 dose cohorts with 3 participants per cohort who will receive intravenous doses of allogeneic bone marrow derived allogeneic mesenchymal stromal cells--0.3 million cells/kg, 1.0 million cells/kg, and 3.0 million cells/kg. We will proceed from the lower dose to the next higher dose if there are no safety concerns for each cohort. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Admission to the Ottawa Hospital Intensive Care Unit
- Receipt of appropriate broad spectrum antibiotics for the suspected/confirmed infectious source and adequate source control according to the opinion of the treating critical care physician
- Within 24 hours of admission to the ICU, receipt of reasonable levels of fluid administration and resuscitation as indicated by:
- Cardiovascular failure that is present within the first 24 hours of admission to the ICU and that is present for at least 4 consecutive hours AND
- Deterioration or lack of improvement in at least 1 additional organ function, 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
Key exclusion criteria (12 listed)
- Another form of shock (cardiogenic, hypovolemic, obstructive) that is considered by the treating critical care physician as the dominant cause of shock
- History of known pulmonary hypertension with a WHO functional class of III or IV
- History of severe pulmonary disease requiring home oxygen
- History of severe cardiac disease 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 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 mesenchymal stromal cellsThe allogeneic mesenchymal stromal cells will be administered intravenously. | Biological | allogeneic mesenchymal stromal cells |
Primary outcome
Number of adverse events as a measure of safety and tolerability
Time frame: 12 months
A historical cohort that met CISS eligibility criteria were previously enrolled to compare the incidence of adverse events with the CISS interventional arm.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2018.
- Derived from this study: PubMed 28960096McIntyre LA, Stewart DJ, Mei SHJ, Courtman D, Watpool I, Granton J, Marshall J, Dos Santos C, Walley KR, Winston BW, Schlosser K, Fergusson DA; Canadian Critical Care Trials Group; Canadian Critical Care Translational Biology Group. Cellular Immunotherapy for Septic Shock. A Phase I Clinical Trial. Am J Respir Crit Care Med. 2018 Feb 1;197(3):337-347. doi: 10.1164/rccm.201705-1006OC.
- Individual participant dataSharing planned: Undecided. The sample size of the interventional arm is very small and the sharing of individual data has privacy and confidentiality implications.
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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Allogeneic mesenchymal stromal cells in people with Septic Shock, run by Ottawa Hospital Research Institute at 1 site 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 8 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: finished, as of the sponsor's last update on 31 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of adverse events as a measure of safety and tolerability (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02421484, which also lists 1 linked publication.
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 31 Oct 2018.