Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT03369275
Other study ID # 201706
Secondary ID
Status Not yet recruiting
Phase Phase 2
First received August 28, 2017
Last updated December 5, 2017
Start date March 2018
Est. completion date October 2020

Study information

Verified date December 2017
Source Ottawa Hospital Research Institute
Contact Josee Champagne
Phone 613-737-8899
Email jochampagne@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 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.


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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 114
Est. completion date October 2020
Est. primary completion date February 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

A participant must meet all three inclusion criteria to be eligible:

1. Admission to an Intensive Care Unit AND

2. 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

3. 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:

1. 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.

2. Hematological failure: platelet count of less than or equal to 100 X 109 /L that has decreased by at least 50 x 109/L.

3. 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.

4. 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:

1. Another form of shock (cardiogenic, hypovolemic, obstructive) that is considered by the treating critical care staff physician as the dominant cause of shock.

2. History of known chronic pulmonary hypertension with a WHO functional class of III or IV

3. History of severe chronic pulmonary disease requiring home oxygen

4. 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.

5. History of severe chronic liver disease (Child class C)

6. 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.

7. Chronic immune suppression (chronic steroid use or chemotherapy)

8. Pregnant or lactating

9. Enrolment in another interventional study

10. Treating physicians' impression is that the participant is moribund and that death is imminent within the subsequent 12 hours of meeting eligibility criteria

11. 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).

12. Less than 18 years of age

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
Cryopreserved Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.
Other:
Placebo
Placebo, with excipients, will be administered intravenously.

Locations

Country Name City State
n/a

Sponsors (4)

Lead Sponsor Collaborator
Ottawa Hospital Research Institute Canadian Institutes of Health Research (CIHR), Ontario Institute for Regenerative Medicine (OIRM), Stem Cell Network

Outcome

Type Measure Description Time frame Safety issue
Primary The reduction in days on mechanical ventilation, or renal replacement therapy, or vasopressors. The number of days free from each of these support measures. Through to 28 days post-randomization
Primary Incidence of treatment-emergent adverse events (Safety and tolerability) Through to 28 days post-randomization
Secondary 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 At baseline, 1, 2, 3 and 7 days post-randomization
Secondary Mortality All-cause mortality Through to 12 months post-randomization
Secondary Organ Failure Scores Sequential Organ Failure Assessment (SOFA) Score Through to 90 days post-randomization
Secondary Organ Support Measures Duration of mechanical ventilation and/or vasopressor agents and/or dialysis/renal replacement therapy Through to 90 days post-randomization
Secondary Length of ICU Stay (in days) Time in ICU Number of elapsed days from admission until ICU discharge, up to one year
Secondary Length of Hospital Stay (in days) Time in Hospital Number of elapsed days from admission until hospital discharge, up to one year
Secondary Hospital Re-Admissions At 28 days, 3 and 12 months post-randomization
Secondary Patient Reported Outcomes-FIM Functional Independence Measure (FIM) 7 days and 6 months post-ICU discharge
Secondary Patient Reported Outcomes-SF 36 SF-36 Score 7 days and 6 months post-ICU discharge
See also
  Status Clinical Trial Phase
Active, not recruiting NCT05095324 - The Biomarker Prediction Model of Septic Risk in Infected Patients
Completed NCT02714595 - Study of Cefiderocol (S-649266) or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens Phase 3
Completed NCT03644030 - Phase Angle, Lean Body Mass Index and Tissue Edema and Immediate Outcome of Cardiac Surgery Patients
Completed NCT02867267 - The Efficacy and Safety of Ta1 for Sepsis Phase 3
Completed NCT04804306 - Sepsis Post Market Clinical Utility Simple Endpoint Study - HUMC
Recruiting NCT05578196 - Fecal Microbial Transplantation in Critically Ill Patients With Severe Infections. N/A
Terminated NCT04117568 - The Role of Emergency Neutrophils and Glycans in Postoperative and Septic Patients
Completed NCT03550794 - Thiamine as a Renal Protective Agent in Septic Shock Phase 2
Completed NCT04332861 - Evaluation of Infection in Obstructing Urolithiasis
Completed NCT04227652 - Control of Fever in Septic Patients N/A
Enrolling by invitation NCT05052203 - Researching the Effects of Sepsis on Quality Of Life, Vitality, Epigenome and Gene Expression During RecoverY From Sepsis
Terminated NCT03335124 - The Effect of Vitamin C, Thiamine and Hydrocortisone on Clinical Course and Outcome in Patients With Severe Sepsis and Septic Shock Phase 4
Recruiting NCT04005001 - Machine Learning Sepsis Alert Notification Using Clinical Data Phase 2
Completed NCT03258684 - Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Sepsis and Septic Shock N/A
Recruiting NCT05217836 - Iron Metabolism Disorders in Patients With Sepsis or Septic Shock.
Completed NCT05018546 - Safety and Efficacy of Different Irrigation System in Retrograde Intrarenal Surgery N/A
Completed NCT03295825 - Heparin Binding Protein in Early Sepsis Diagnosis N/A
Not yet recruiting NCT06045130 - PUFAs in Preterm Infants
Not yet recruiting NCT05361135 - 18-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in S. Aureus Bacteraemia N/A
Not yet recruiting NCT05443854 - Impact of Aminoglycosides-based Antibiotics Combination and Protective Isolation on Outcomes in Critically-ill Neutropenic Patients With Sepsis: (Combination-Lock01) Phase 3