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Cellular Immunotherapy for Septic Shock: A Phase I Trial (CISS)

Primary Purpose

Septic Shock

Status

Completed

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

Allogeneic mesenchymal stromal cells

About this trial

This is an interventional treatment trial for Septic Shock focused on measuring Phase I clinical trial, stem cell, mesenchymal stromal cell, mesenchymal stem cell

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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).
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

Sites / Locations

The Ottawa Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

allogeneic mesenchymal stromal cells

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT02421484

First Posted

February 8, 2015

Last Updated

October 30, 2018

Sponsor

Ottawa Hospital Research Institute

Collaborators

Canadian Institutes of Health Research (CIHR)

1. Study Identification

Unique Protocol Identification Number

NCT02421484

Brief Title

Cellular Immunotherapy for Septic Shock: A Phase I Trial

Acronym

CISS

Official Title

Cellular Immunotherapy for Septic Shock: A Phase I Trial

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Completed

Study Start Date

May 2015 (undefined)

Primary Completion Date

June 2016 (Actual)

Study Completion Date

October 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ottawa Hospital Research Institute

Collaborators

Canadian Institutes of Health Research (CIHR)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Septic Shock

Keywords

Phase I clinical trial, stem cell, mesenchymal stromal cell, mesenchymal stem cell

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

allogeneic mesenchymal stromal cells

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Allogeneic mesenchymal stromal cells

Intervention Description

The allogeneic mesenchymal stromal cells will be administered intravenously.

Primary Outcome Measure Information:

Title

Number of adverse events as a measure of safety and tolerability

Description

A historical cohort that met CISS eligibility criteria were previously enrolled to compare the incidence of adverse events with the CISS interventional arm.

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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). 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lauralyn McIntyre, MD

Organizational Affiliation

Ottawa Hospital Research Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Ottawa Hospital

City

Ottawa

State/Province

Ontario

ZIP/Postal Code

K1H 8L9

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

The sample size of the interventional arm is very small and the sharing of individual data has privacy and confidentiality implications.

Citations:

PubMed Identifier

28960096

Citation

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.

Results Reference

derived

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Cellular Immunotherapy for Septic Shock: A Phase I Trial

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