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Effect of Remote Ischemic Conditioning on Trauma Patients With Hemorrhagic Shock

Primary Purpose

Hemorrhagic Shock

Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Pneumatic tourniquet
Sponsored by
Unity Health Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Hemorrhagic Shock focused on measuring Hemorrhagic Shock, Remote Ischemic Conditioning

Eligibility Criteria

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

Inclusion Criteria:

  • Age ≥16 years of age or estimated weight ≥50kgs if age is unknown;
  • Victim of blunt or penetrating trauma
  • Hemorrhagic shock defined as:
  • One or more episodes of systolic blood pressure ≤90mmHg at any time prior to enrollment into the study;
  • An identified source of blood loss (abdomen, chest, pelvis/retroperitoneum, extremities, external) or
  • Blood products (RBC, Platelets, Plasma, etc.) has been ordered to the trauma room.
  • Admitted to St. Michael's Hospital directly from the scene of injury within 3 hours of the injury
  • Application and completion of Remote Ischemic Conditioning (RIC) within 4 hours of the injury

Exclusion Criteria:

  • Pregnancy
  • Non-hemorrhagic shock (i.e. tension pneumothorax, cardiac tamponade, spinal shock, etc.)
  • Major burns > 20% total body surface area
  • Fracture of both lower extremities (i.e. traumatic amputation, fractures)
  • Absence of vital signs prior to admission, ongoing CPR, possibly dead on admission or not expected to survive beyond a few hours.
  • Injury in both legs (traumatic amputation, fractures, etc.)
  • Patients with a systolic blood pressure above 200mmHg
  • Patients treated with anticoagulants, antiplatelet therapy (Warfarin, Aspirin), steroids or with a known bleeding disorder or known abnormality of blood flow to the limb (if known)
  • Patients with osteoporosis or other bone disorders, peripheral nerve injury, abnormal nerve supply, peripheral neuropathy (if known) or preexisting traumatic injury to the limb.
  • Morbid obesity (largest cuff size won't fit)
  • If RIC is done clinically before research protocol begins.

Sites / Locations

  • St. Michael's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Experimental

Arm Label

Sham Remote Ischemic Conditioning

Remote Ischemic Conditioning

Arm Description

Sham inflation of pneumatic tourniquet pressure cuff at 0 mmHg on the thigh for 5 minutes and release for 5 minutes (repeated for 4 cycles) applied to trauma patients on arrival to hospital

Inflation of pneumatic tourniquet pressure cuff at 250mmHg on the thigh for 5 minutes and release for 5 minutes (repeated for 4 cycles) applied to trauma patients on arrival to hospital

Outcomes

Primary Outcome Measures

Neutrophil Oxidative Burst Activity
Change in neutrophil oxidative burst activity (dihydrorhodamine, DHR) over 24 hours from admission. Measured by flow cytometry using whole blood samples.
Neutrophil Oxidative Burst Activity (PMA Stimulated)
Change in PMA stimulated neutrophil oxidative burst activity (dihydrorhodamine, DHR) over 24 hours. Measured by flow cytometry using whole blood samples.
Neutrophil Adhesion Molecule Expression (CD11b)
Change in neutrophil adhesion molecule (CD11b) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples.
Neutrophil Adhesion Molecule Expression (CD62L)
Change in neutrophil adhesion molecule (CD62L) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples.
Endothelial Injury (Heparan Sulfate)
Change in plasma levels of endothelial injury marker Heparan Sulfate over 24 hours from Admission
Endothelial Injury (Hyaluronan)
Change in plasma levels of endothelial injury marker Hyaluronan over 24 hours from Admission
Endothelial Injury (Syndecan-1)
Change in plasma levels of endothelial injury marker Syndecan-1 over 24 hours from Admission
Plasma TNF-α
Change in plasma levels of inflammatory mediator TNF-α over 24 hours from Admission
Plasma IL-6
Change in plasma levels of inflammatory mediator IL-6 over 24 hours from Admission
Plasma IL-8
Change in plasma levels of inflammatory mediator IL-8 over 24 hours from Admission
Plasma IL-10
Change in plasma levels of anti-inflammatory mediator IL-10 over 24 hours from Admission
ROTEM EXTEM CT
Change in ROTEM parameter Clotting Time (CT) over 24 hours from Admission
ROTEM EXTEM CFT
Change in ROTEM parameter Clot Formation Time (CFT) over 24 hours from Admission
ROTEM EXTEM A10
Change in ROTEM parameter A10 over 24 hours from Admission
ROTEM EXTEM Alpha Angle
Change in ROTEM parameter Alpha Angle over 24 hours from Admission
ROTEM EXTEM ML
Change in ROTEM parameter maximum lysis (ML) over 24 hours from Admission
Plasma D-Dimer
Change in plasma D-Dimer levels over 24 hours from Admission
Plasma Protein C
Change in plasma Protein C levels over 24 hours from Admission
Plasma Fibrinogen
Change in plasma fibrinogen levels over 24 hours from Admission

Secondary Outcome Measures

Ventilator Free Days
Secondary clinical outcomes
ICU Free Days
Secondary clinical outcomes
Hospital Free Days
Secondary clinical outcomes
Nosocomial Infections
Secondary clinical outcomes
24 Hour Mortality
Secondary clinical outcomes
28 Day Mortality
Secondary clinical outcomes

Full Information

First Posted
February 18, 2014
Last Updated
May 10, 2023
Sponsor
Unity Health Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT02071290
Brief Title
Effect of Remote Ischemic Conditioning on Trauma Patients With Hemorrhagic Shock
Official Title
Effect of Remote Ischemic Conditioning on Neutrophil Function and the Immune-Inflammatory and Coagulation Profiles in Trauma Patients With Hemorrhagic Shock
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
May 2015 (Actual)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Unity Health Toronto

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the study is to evaluate whether remote ischemic conditioning is a safe and effective intervention to prevent the development of inflammation and coagulopathy in trauma patients with hemorrhagic shock.
Detailed Description
Dysfunction of vital organs is one of the major reasons why trauma victims die after sustaining a major injury, even though the organs themselves may not have been directly injured. The inability to clot blood as a result of inflammation further contributes to complications in a majority of these patients. One intervention proposed to protect against impaired organ function is called "Remote Ischemic Conditioning", wherein application of intermittent occlusion and release of blood flow to the arm by sequentially inflating and deflating a blood pressure cuff can protect against the development of distant organ injury and inflammation following a severe traumatic event. In a pilot study, we will investigate the effects of remote ischemic conditioning in trauma patients with hemorrhagic shock, with a view to evaluate its effects on the immune system and coagulation profiles, both of which are known to be deranged in these patients. These studies will potentially benefit patients and will serve as a proof of principle for the use of remote ischemic conditioning in the trauma setting.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemorrhagic Shock
Keywords
Hemorrhagic Shock, Remote Ischemic Conditioning

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sham Remote Ischemic Conditioning
Arm Type
Sham Comparator
Arm Description
Sham inflation of pneumatic tourniquet pressure cuff at 0 mmHg on the thigh for 5 minutes and release for 5 minutes (repeated for 4 cycles) applied to trauma patients on arrival to hospital
Arm Title
Remote Ischemic Conditioning
Arm Type
Experimental
Arm Description
Inflation of pneumatic tourniquet pressure cuff at 250mmHg on the thigh for 5 minutes and release for 5 minutes (repeated for 4 cycles) applied to trauma patients on arrival to hospital
Intervention Type
Device
Intervention Name(s)
Pneumatic tourniquet
Intervention Description
Four cycles of brief occlusion of bloodflow to the thigh (5 minutes) followed by reperfusion (5 minutes) using a pneumatic tourniquet Remote Ischemic Conditioning
Primary Outcome Measure Information:
Title
Neutrophil Oxidative Burst Activity
Description
Change in neutrophil oxidative burst activity (dihydrorhodamine, DHR) over 24 hours from admission. Measured by flow cytometry using whole blood samples.
Time Frame
0 (Admission), 1, 3, and 24 hours after intervention
Title
Neutrophil Oxidative Burst Activity (PMA Stimulated)
Description
Change in PMA stimulated neutrophil oxidative burst activity (dihydrorhodamine, DHR) over 24 hours. Measured by flow cytometry using whole blood samples.
Time Frame
0 (Admission), 1, 3, and 24 hours after intervention
Title
Neutrophil Adhesion Molecule Expression (CD11b)
Description
Change in neutrophil adhesion molecule (CD11b) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples.
Time Frame
0 (Admission), 1, 3, 24 hours after intervention
Title
Neutrophil Adhesion Molecule Expression (CD62L)
Description
Change in neutrophil adhesion molecule (CD62L) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples.
Time Frame
0 (Admission), 1, 3, and 24 hours after intervention
Title
Endothelial Injury (Heparan Sulfate)
Description
Change in plasma levels of endothelial injury marker Heparan Sulfate over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, and 24 hours after intervention
Title
Endothelial Injury (Hyaluronan)
Description
Change in plasma levels of endothelial injury marker Hyaluronan over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, 24 hours
Title
Endothelial Injury (Syndecan-1)
Description
Change in plasma levels of endothelial injury marker Syndecan-1 over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, and 24 hours after intervention
Title
Plasma TNF-α
Description
Change in plasma levels of inflammatory mediator TNF-α over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, and 24 hours after intervention
Title
Plasma IL-6
Description
Change in plasma levels of inflammatory mediator IL-6 over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, 24 hours
Title
Plasma IL-8
Description
Change in plasma levels of inflammatory mediator IL-8 over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, 24 hours
Title
Plasma IL-10
Description
Change in plasma levels of anti-inflammatory mediator IL-10 over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, 24 hours
Title
ROTEM EXTEM CT
Description
Change in ROTEM parameter Clotting Time (CT) over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, 24 hours
Title
ROTEM EXTEM CFT
Description
Change in ROTEM parameter Clot Formation Time (CFT) over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, 24 hours
Title
ROTEM EXTEM A10
Description
Change in ROTEM parameter A10 over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, 24 hours
Title
ROTEM EXTEM Alpha Angle
Description
Change in ROTEM parameter Alpha Angle over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, 24 hours
Title
ROTEM EXTEM ML
Description
Change in ROTEM parameter maximum lysis (ML) over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, 24 hours
Title
Plasma D-Dimer
Description
Change in plasma D-Dimer levels over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, 24 hours
Title
Plasma Protein C
Description
Change in plasma Protein C levels over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, 24 hours
Title
Plasma Fibrinogen
Description
Change in plasma fibrinogen levels over 24 hours from Admission
Time Frame
0 (Admission), 1, 3, 24 hours
Secondary Outcome Measure Information:
Title
Ventilator Free Days
Description
Secondary clinical outcomes
Time Frame
up to 28 days or discharge
Title
ICU Free Days
Description
Secondary clinical outcomes
Time Frame
up to 28 days or discharge
Title
Hospital Free Days
Description
Secondary clinical outcomes
Time Frame
up to 28 days or discharge
Title
Nosocomial Infections
Description
Secondary clinical outcomes
Time Frame
up to 28 days or discharge
Title
24 Hour Mortality
Description
Secondary clinical outcomes
Time Frame
up to 28 days or discharge
Title
28 Day Mortality
Description
Secondary clinical outcomes
Time Frame
up to 28 days or discharge

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥16 years of age or estimated weight ≥50kgs if age is unknown; Victim of blunt or penetrating trauma Hemorrhagic shock defined as: One or more episodes of systolic blood pressure ≤90mmHg at any time prior to enrollment into the study; An identified source of blood loss (abdomen, chest, pelvis/retroperitoneum, extremities, external) or Blood products (RBC, Platelets, Plasma, etc.) has been ordered to the trauma room. Admitted to St. Michael's Hospital directly from the scene of injury within 3 hours of the injury Application and completion of Remote Ischemic Conditioning (RIC) within 4 hours of the injury Exclusion Criteria: Pregnancy Non-hemorrhagic shock (i.e. tension pneumothorax, cardiac tamponade, spinal shock, etc.) Major burns > 20% total body surface area Fracture of both lower extremities (i.e. traumatic amputation, fractures) Absence of vital signs prior to admission, ongoing CPR, possibly dead on admission or not expected to survive beyond a few hours. Injury in both legs (traumatic amputation, fractures, etc.) Patients with a systolic blood pressure above 200mmHg Patients treated with anticoagulants, antiplatelet therapy (Warfarin, Aspirin), steroids or with a known bleeding disorder or known abnormality of blood flow to the limb (if known) Patients with osteoporosis or other bone disorders, peripheral nerve injury, abnormal nerve supply, peripheral neuropathy (if known) or preexisting traumatic injury to the limb. Morbid obesity (largest cuff size won't fit) If RIC is done clinically before research protocol begins.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ori D Rotstein, MD
Organizational Affiliation
Unity Health Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B1W8
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

Effect of Remote Ischemic Conditioning on Trauma Patients With Hemorrhagic Shock

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