Cellular Immunotherapy for Septic Shock

NCT03369275 | Unknown Phase 2 DMC

• 1 other identifier: 201706
• Study Type: interventional
• Target: 114
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Septic Shock; Sepsis; Pathologic Processes; Shock; Infection; Systemic Inflammatory Response Syndrome; Inflammation

Keywords

Mesenchymal Stem Cells; Mesenchymal Stromal Cells; Randomized Controlled Trial; Cryopreserved; Allogeneic; Phase II

Outcome Measures

Primary Outcomes (2)

• 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

• Incidence of treatment-emergent adverse events (Safety and tolerability)

  Through to 28 days post-randomization

Secondary Outcomes (9)

• Biological endpoints as markers of vascular permeability

  At baseline, 1, 2, 3 and 7 days post-randomization

• Mortality

  Through to 12 months post-randomization

• Organ Failure Scores

  Through to 90 days post-randomization

• Organ Support Measures

  Through to 90 days post-randomization

• Length of ICU Stay (in days)

  Number of elapsed days from admission until ICU discharge, up to one year

Study Arms (2)

Mesenchymal Stromal Cells (MSCs)

EXPERIMENTAL

Intravenous infusion of 300 million Allogeneic, Bone Marrow-Derived Human Mesenchymal Stromal Cells

Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells

Placebo

PLACEBO COMPARATOR

Intravenous infusion of Placebo, with excipients

Other: Placebo

Interventions

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells BIOLOGICAL

Cryopreserved Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.

Mesenchymal Stromal Cells (MSCs)

Placebo OTHER

Placebo, with excipients, will be administered intravenously.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR): collaborator
• Ottawa Hospital Research Institute: lead
• Ontario Institute for Regenerative Medicine (OIRM): collaborator
• Stem Cell Network: collaborator

MeSH Terms

Conditions

Shock, Septic; Sepsis; Pathologic Processes; Shock; Infections; Systemic Inflammatory Response Syndrome; Inflammation

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms

Study Officials

• Lauralyn McIntyre, MD

  The Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Josee Champagne

CONTACT

613-737-8899; jochampagne@ohri.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2017
• First Posted: December 11, 2017
• Study Start: March 1, 2018
• Primary Completion: February 1, 2020
• Study Completion: October 1, 2020
• Last Updated: December 11, 2017

Record last verified: 2017-12