Hemorrhagic Shock
Conditions
Keywords
Hemorrhagic Shock, Remote Ischemic Conditioning
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.
Interventions
DEVICEPneumatic tourniquet
Four cycles of brief occlusion of bloodflow to the thigh (5 minutes) followed by reperfusion (5 minutes) using a pneumatic tourniquet Remote Ischemic Conditioning
Sponsors
Unity Health Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ROTEM EXTEM Alpha Angle | 0 (Admission), 1, 3, 24 hours | Change in ROTEM parameter Alpha Angle over 24 hours from Admission |
| Plasma IL-6 | 0 (Admission), 1, 3, 24 hours | Change in plasma levels of inflammatory mediator IL-6 over 24 hours from Admission |
| Plasma IL-8 | 0 (Admission), 1, 3, 24 hours | Change in plasma levels of inflammatory mediator IL-8 over 24 hours from Admission |
| Plasma IL-10 | 0 (Admission), 1, 3, 24 hours | Change in plasma levels of anti-inflammatory mediator IL-10 over 24 hours from Admission |
| ROTEM EXTEM CT | 0 (Admission), 1, 3, 24 hours | Change in ROTEM parameter Clotting Time (CT) over 24 hours from Admission |
| ROTEM EXTEM CFT | 0 (Admission), 1, 3, 24 hours | Change in ROTEM parameter Clot Formation Time (CFT) over 24 hours from Admission |
| ROTEM EXTEM A10 | 0 (Admission), 1, 3, 24 hours | Change in ROTEM parameter A10 over 24 hours from Admission |
| Plasma Protein C | 0 (Admission), 1, 3, 24 hours | Change in plasma Protein C levels over 24 hours from Admission |
| Plasma Fibrinogen | 0 (Admission), 1, 3, 24 hours | Change in plasma fibrinogen levels over 24 hours from Admission |
| ROTEM EXTEM ML | 0 (Admission), 1, 3, 24 hours | Change in ROTEM parameter maximum lysis (ML) over 24 hours from Admission |
| Plasma D-Dimer | 0 (Admission), 1, 3, 24 hours | Change in plasma D-Dimer levels over 24 hours from Admission |
| Neutrophil Oxidative Burst Activity | 0 (Admission), 1, 3, and 24 hours after intervention | 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) | 0 (Admission), 1, 3, and 24 hours after intervention | 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) | 0 (Admission), 1, 3, 24 hours after intervention | 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) | 0 (Admission), 1, 3, and 24 hours after intervention | Change in neutrophil adhesion molecule (CD62L) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples. |
| Endothelial Injury (Heparan Sulfate) | 0 (Admission), 1, 3, and 24 hours after intervention | Change in plasma levels of endothelial injury marker Heparan Sulfate over 24 hours from Admission |
| Endothelial Injury (Hyaluronan) | 0 (Admission), 1, 3, 24 hours | Change in plasma levels of endothelial injury marker Hyaluronan over 24 hours from Admission |
| Endothelial Injury (Syndecan-1) | 0 (Admission), 1, 3, and 24 hours after intervention | Change in plasma levels of endothelial injury marker Syndecan-1 over 24 hours from Admission |
| Plasma TNF-α | 0 (Admission), 1, 3, and 24 hours after intervention | Change in plasma levels of inflammatory mediator TNF-α over 24 hours from Admission |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU Free Days | up to 28 days or discharge | Secondary clinical outcomes |
| Hospital Free Days | up to 28 days or discharge | Secondary clinical outcomes |
| Nosocomial Infections | up to 28 days or discharge | Secondary clinical outcomes |
| 24 Hour Mortality | up to 28 days or discharge | Secondary clinical outcomes |
| 28 Day Mortality | up to 28 days or discharge | Secondary clinical outcomes |
| Ventilator Free Days | up to 28 days or discharge | Secondary clinical outcomes |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sham Remote Ischemic Conditioning 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 | 21 |
| Remote Ischemic Conditioning 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 | 18 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Sham Remote Ischemic Conditioning | Remote Ischemic Conditioning |
|---|---|---|---|
| Age, Continuous | 39 years STANDARD_DEVIATION 17 | 37 years STANDARD_DEVIATION 17 | 40 years STANDARD_DEVIATION 17 |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Region of Enrollment Canada | 39 Participants | 21 Participants | 18 Participants |
| Sex: Female, Male Female | 9 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Male | 30 Participants | 16 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 21 | 1 / 18 |
| other Total, other adverse events | 0 / 21 | 0 / 18 |
| serious Total, serious adverse events | 6 / 21 | 9 / 18 |
Outcome results
Primary
Endothelial Injury (Heparan Sulfate)
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Endothelial Injury (Heparan Sulfate) | Admission | 6.7 ng/mL |
| Sham Remote Ischemic Conditioning | Endothelial Injury (Heparan Sulfate) | 1 Hour | 3.3 ng/mL |
| Sham Remote Ischemic Conditioning | Endothelial Injury (Heparan Sulfate) | 24 Hour | 3.0 ng/mL |
| Sham Remote Ischemic Conditioning | Endothelial Injury (Heparan Sulfate) | 3 Hour | 3.3 ng/mL |
| Remote Ischemic Conditioning | Endothelial Injury (Heparan Sulfate) | 24 Hour | 3.7 ng/mL |
| Remote Ischemic Conditioning | Endothelial Injury (Heparan Sulfate) | Admission | 6.0 ng/mL |
| Remote Ischemic Conditioning | Endothelial Injury (Heparan Sulfate) | 1 Hour | 4.9 ng/mL |
| Remote Ischemic Conditioning | Endothelial Injury (Heparan Sulfate) | 3 Hour | 3.6 ng/mL |
p-value: 0.646Mixed Models Analysis
Primary
Endothelial Injury (Hyaluronan)
Change in plasma levels of endothelial injury marker Hyaluronan over 24 hours from Admission
Time frame: 0 (Admission), 1, 3, 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Endothelial Injury (Hyaluronan) | Admission | 45.9 ng/mL |
| Sham Remote Ischemic Conditioning | Endothelial Injury (Hyaluronan) | 1 Hour | 35.6 ng/mL |
| Sham Remote Ischemic Conditioning | Endothelial Injury (Hyaluronan) | 3 Hour | 19.2 ng/mL |
| Sham Remote Ischemic Conditioning | Endothelial Injury (Hyaluronan) | 24 Hour | 54.9 ng/mL |
| Remote Ischemic Conditioning | Endothelial Injury (Hyaluronan) | 24 Hour | 67.1 ng/mL |
| Remote Ischemic Conditioning | Endothelial Injury (Hyaluronan) | Admission | 36.6 ng/mL |
| Remote Ischemic Conditioning | Endothelial Injury (Hyaluronan) | 3 Hour | 26.5 ng/mL |
| Remote Ischemic Conditioning | Endothelial Injury (Hyaluronan) | 1 Hour | 43.1 ng/mL |
p-value: 0.757Mixed Models Analysis
Primary
Endothelial Injury (Syndecan-1)
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Endothelial Injury (Syndecan-1) | Admission | 25.3 ng/mL |
| Sham Remote Ischemic Conditioning | Endothelial Injury (Syndecan-1) | 1 Hour | 35.0 ng/mL |
| Sham Remote Ischemic Conditioning | Endothelial Injury (Syndecan-1) | 3 Hour | 39.4 ng/mL |
| Sham Remote Ischemic Conditioning | Endothelial Injury (Syndecan-1) | 24 Hour | 24.3 ng/mL |
| Remote Ischemic Conditioning | Endothelial Injury (Syndecan-1) | 24 Hour | 38.3 ng/mL |
| Remote Ischemic Conditioning | Endothelial Injury (Syndecan-1) | Admission | 27.2 ng/mL |
| Remote Ischemic Conditioning | Endothelial Injury (Syndecan-1) | 3 Hour | 48 ng/mL |
| Remote Ischemic Conditioning | Endothelial Injury (Syndecan-1) | 1 Hour | 31.6 ng/mL |
p-value: 0.075Mixed Models Analysis
Primary
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.
Time frame: 0 (Admission), 1, 3, 24 hours after intervention
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD11b) | 3 Hour | 5889 Median Fluorescence Intensity |
| Sham Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD11b) | Admission | 5492 Median Fluorescence Intensity |
| Sham Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD11b) | 24 Hour | 9998 Median Fluorescence Intensity |
| Sham Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD11b) | 1 Hour | 5108 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD11b) | 24 Hour | 6013 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD11b) | Admission | 4341 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD11b) | 3 Hour | 6362 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD11b) | 1 Hour | 5808 Median Fluorescence Intensity |
p-value: 0.597Mixed Models Analysis
Primary
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.
Time frame: 0 (Admission), 1, 3, and 24 hours after intervention
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD62L) | Admission | 5913 Median Fluorescence Intensity |
| Sham Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD62L) | 1 Hour | 5404 Median Fluorescence Intensity |
| Sham Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD62L) | 3 Hour | 4414 Median Fluorescence Intensity |
| Sham Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD62L) | 24 Hour | 3742 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD62L) | 24 Hour | 3569 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD62L) | Admission | 5556 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD62L) | 3 Hour | 4995 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Adhesion Molecule Expression (CD62L) | 1 Hour | 5452 Median Fluorescence Intensity |
p-value: 0.307Mixed Models Analysis
Primary
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.
Time frame: 0 (Admission), 1, 3, and 24 hours after intervention
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity | Admission | 302 Median Fluorescence Intensity |
| Sham Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity | 1 Hour | 298 Median Fluorescence Intensity |
| Sham Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity | 3 Hour | 229 Median Fluorescence Intensity |
| Sham Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity | 24 Hour | 337 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity | 24 Hour | 461 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity | Admission | 302 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity | 3 Hour | 202 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity | 1 Hour | 268 Median Fluorescence Intensity |
p-value: 0.56Mixed Models Analysis
Primary
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.
Time frame: 0 (Admission), 1, 3, and 24 hours after intervention
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity (PMA Stimulated) | 1 Hour | 27041 Median Fluorescence Intensity |
| Sham Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity (PMA Stimulated) | Admission | 28812 Median Fluorescence Intensity |
| Sham Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity (PMA Stimulated) | 3 Hour | 19027 Median Fluorescence Intensity |
| Sham Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity (PMA Stimulated) | 24 Hour | 4680 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity (PMA Stimulated) | 24 Hour | 2667 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity (PMA Stimulated) | Admission | 14772 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity (PMA Stimulated) | 1 Hour | 13044 Median Fluorescence Intensity |
| Remote Ischemic Conditioning | Neutrophil Oxidative Burst Activity (PMA Stimulated) | 3 Hour | 8753 Median Fluorescence Intensity |
p-value: 0.287Mixed Models Analysis
Primary
Plasma D-Dimer
Change in plasma D-Dimer levels over 24 hours from Admission
Time frame: 0 (Admission), 1, 3, 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Plasma D-Dimer | 24 Hour | 1.64 ug/mL |
| Sham Remote Ischemic Conditioning | Plasma D-Dimer | 1 Hour | 0.59 ug/mL |
| Sham Remote Ischemic Conditioning | Plasma D-Dimer | Admission | 0.96 ug/mL |
| Sham Remote Ischemic Conditioning | Plasma D-Dimer | 3 Hour | 0.85 ug/mL |
| Remote Ischemic Conditioning | Plasma D-Dimer | 24 Hour | 1.70 ug/mL |
| Remote Ischemic Conditioning | Plasma D-Dimer | 3 Hour | 1.53 ug/mL |
| Remote Ischemic Conditioning | Plasma D-Dimer | Admission | 1.56 ug/mL |
| Remote Ischemic Conditioning | Plasma D-Dimer | 1 Hour | 1.50 ug/mL |
p-value: 0.371Mixed Models Analysis
Primary
Plasma Fibrinogen
Change in plasma fibrinogen levels over 24 hours from Admission
Time frame: 0 (Admission), 1, 3, 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Plasma Fibrinogen | Admission | 1.65 g/mL |
| Sham Remote Ischemic Conditioning | Plasma Fibrinogen | 1 Hour | 2.09 g/mL |
| Sham Remote Ischemic Conditioning | Plasma Fibrinogen | 3 Hour | 2.11 g/mL |
| Sham Remote Ischemic Conditioning | Plasma Fibrinogen | 24 Hour | 3.91 g/mL |
| Remote Ischemic Conditioning | Plasma Fibrinogen | 24 Hour | 3.55 g/mL |
| Remote Ischemic Conditioning | Plasma Fibrinogen | Admission | 2.44 g/mL |
| Remote Ischemic Conditioning | Plasma Fibrinogen | 3 Hour | 2.35 g/mL |
| Remote Ischemic Conditioning | Plasma Fibrinogen | 1 Hour | 2.41 g/mL |
p-value: 0.829Mixed Models Analysis
Primary
Plasma IL-10
Change in plasma levels of anti-inflammatory mediator IL-10 over 24 hours from Admission
Time frame: 0 (Admission), 1, 3, 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Plasma IL-10 | Admission | 1.93 pg/mL |
| Sham Remote Ischemic Conditioning | Plasma IL-10 | 1 Hour | 5.88 pg/mL |
| Sham Remote Ischemic Conditioning | Plasma IL-10 | 3 Hour | 5.56 pg/mL |
| Sham Remote Ischemic Conditioning | Plasma IL-10 | 24 Hour | 3.15 pg/mL |
| Remote Ischemic Conditioning | Plasma IL-10 | 24 Hour | 2.11 pg/mL |
| Remote Ischemic Conditioning | Plasma IL-10 | Admission | 3.61 pg/mL |
| Remote Ischemic Conditioning | Plasma IL-10 | 3 Hour | 6.20 pg/mL |
| Remote Ischemic Conditioning | Plasma IL-10 | 1 Hour | 8.58 pg/mL |
p-value: 0.661Mixed Models Analysis
Primary
Plasma IL-6
Change in plasma levels of inflammatory mediator IL-6 over 24 hours from Admission
Time frame: 0 (Admission), 1, 3, 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Plasma IL-6 | Admission | 7.73 pg/mL |
| Sham Remote Ischemic Conditioning | Plasma IL-6 | 1 Hour | 11.95 pg/mL |
| Sham Remote Ischemic Conditioning | Plasma IL-6 | 3 Hour | 18.77 pg/mL |
| Sham Remote Ischemic Conditioning | Plasma IL-6 | 24 Hour | 65.72 pg/mL |
| Remote Ischemic Conditioning | Plasma IL-6 | 24 Hour | 51.56 pg/mL |
| Remote Ischemic Conditioning | Plasma IL-6 | Admission | 8.04 pg/mL |
| Remote Ischemic Conditioning | Plasma IL-6 | 3 Hour | 23.30 pg/mL |
| Remote Ischemic Conditioning | Plasma IL-6 | 1 Hour | 21.62 pg/mL |
p-value: 0.637Mixed Models Analysis
Primary
Plasma IL-8
Change in plasma levels of inflammatory mediator IL-8 over 24 hours from Admission
Time frame: 0 (Admission), 1, 3, 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Plasma IL-8 | Admission | 7.1 pg/mL |
| Sham Remote Ischemic Conditioning | Plasma IL-8 | 1 Hour | 6.63 pg/mL |
| Sham Remote Ischemic Conditioning | Plasma IL-8 | 3 Hour | 9.85 pg/mL |
| Sham Remote Ischemic Conditioning | Plasma IL-8 | 24 Hour | 15.12 pg/mL |
| Remote Ischemic Conditioning | Plasma IL-8 | 24 Hour | 9.53 pg/mL |
| Remote Ischemic Conditioning | Plasma IL-8 | Admission | 4.56 pg/mL |
| Remote Ischemic Conditioning | Plasma IL-8 | 3 Hour | 7.98 pg/mL |
| Remote Ischemic Conditioning | Plasma IL-8 | 1 Hour | 5.81 pg/mL |
p-value: 0.664Mixed Models Analysis
Primary
Plasma Protein C
Change in plasma Protein C levels over 24 hours from Admission
Time frame: 0 (Admission), 1, 3, 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Plasma Protein C | Admission | 0.65 U/mL |
| Sham Remote Ischemic Conditioning | Plasma Protein C | 1 Hour | 0.62 U/mL |
| Sham Remote Ischemic Conditioning | Plasma Protein C | 3 Hour | 0.70 U/mL |
| Sham Remote Ischemic Conditioning | Plasma Protein C | 24 Hour | 0.82 U/mL |
| Remote Ischemic Conditioning | Plasma Protein C | 24 Hour | 0.75 U/mL |
| Remote Ischemic Conditioning | Plasma Protein C | Admission | 0.71 U/mL |
| Remote Ischemic Conditioning | Plasma Protein C | 3 Hour | 0.74 U/mL |
| Remote Ischemic Conditioning | Plasma Protein C | 1 Hour | 0.70 U/mL |
p-value: 0.106Mixed Models Analysis
Primary
Plasma TNF-α
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | Plasma TNF-α | Admission | 2.15 pg/mL |
| Sham Remote Ischemic Conditioning | Plasma TNF-α | 1 Hour | 1.97 pg/mL |
| Sham Remote Ischemic Conditioning | Plasma TNF-α | 3 Hour | 1.95 pg/mL |
| Sham Remote Ischemic Conditioning | Plasma TNF-α | 24 Hour | 2.59 pg/mL |
| Remote Ischemic Conditioning | Plasma TNF-α | 24 Hour | 2.72 pg/mL |
| Remote Ischemic Conditioning | Plasma TNF-α | Admission | 2.67 pg/mL |
| Remote Ischemic Conditioning | Plasma TNF-α | 3 Hour | 2.15 pg/mL |
| Remote Ischemic Conditioning | Plasma TNF-α | 1 Hour | 2.34 pg/mL |
p-value: 0.967Mixed Models Analysis
Primary
ROTEM EXTEM A10
Change in ROTEM parameter A10 over 24 hours from Admission
Time frame: 0 (Admission), 1, 3, 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | ROTEM EXTEM A10 | Admission | 54 mm |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM A10 | 1 Hour | 52 mm |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM A10 | 3 Hour | 46 mm |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM A10 | 24 Hour | 52 mm |
| Remote Ischemic Conditioning | ROTEM EXTEM A10 | 24 Hour | 54 mm |
| Remote Ischemic Conditioning | ROTEM EXTEM A10 | Admission | 56 mm |
| Remote Ischemic Conditioning | ROTEM EXTEM A10 | 3 Hour | 51 mm |
| Remote Ischemic Conditioning | ROTEM EXTEM A10 | 1 Hour | 48 mm |
p-value: 0.353Mixed Models Analysis
Primary
ROTEM EXTEM Alpha Angle
Change in ROTEM parameter Alpha Angle over 24 hours from Admission
Time frame: 0 (Admission), 1, 3, 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | ROTEM EXTEM Alpha Angle | Admission | 72 Degrees |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM Alpha Angle | 1 Hour | 71 Degrees |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM Alpha Angle | 3 Hour | 68 Degrees |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM Alpha Angle | 24 Hour | 73 Degrees |
| Remote Ischemic Conditioning | ROTEM EXTEM Alpha Angle | 24 Hour | 72 Degrees |
| Remote Ischemic Conditioning | ROTEM EXTEM Alpha Angle | Admission | 75 Degrees |
| Remote Ischemic Conditioning | ROTEM EXTEM Alpha Angle | 3 Hour | 69 Degrees |
| Remote Ischemic Conditioning | ROTEM EXTEM Alpha Angle | 1 Hour | 71 Degrees |
p-value: 0.99Mixed Models Analysis
Primary
ROTEM EXTEM CFT
Change in ROTEM parameter Clot Formation Time (CFT) over 24 hours from Admission
Time frame: 0 (Admission), 1, 3, 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | ROTEM EXTEM CFT | Admission | 90 Seconds |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM CFT | 1 Hour | 96 Seconds |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM CFT | 3 Hour | 125 Seconds |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM CFT | 24 Hour | 102 Seconds |
| Remote Ischemic Conditioning | ROTEM EXTEM CFT | 24 Hour | 91 Seconds |
| Remote Ischemic Conditioning | ROTEM EXTEM CFT | Admission | 73 Seconds |
| Remote Ischemic Conditioning | ROTEM EXTEM CFT | 3 Hour | 103 Seconds |
| Remote Ischemic Conditioning | ROTEM EXTEM CFT | 1 Hour | 108 Seconds |
p-value: 0.437Mixed Models Analysis
Primary
ROTEM EXTEM CT
Change in ROTEM parameter Clotting Time (CT) over 24 hours from Admission
Time frame: 0 (Admission), 1, 3, 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | ROTEM EXTEM CT | Admission | 71 Seconds |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM CT | 1 Hour | 64 Seconds |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM CT | 3 Hour | 68 Seconds |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM CT | 24 Hour | 66 Seconds |
| Remote Ischemic Conditioning | ROTEM EXTEM CT | 24 Hour | 71 Seconds |
| Remote Ischemic Conditioning | ROTEM EXTEM CT | Admission | 65 Seconds |
| Remote Ischemic Conditioning | ROTEM EXTEM CT | 3 Hour | 59 Seconds |
| Remote Ischemic Conditioning | ROTEM EXTEM CT | 1 Hour | 62 Seconds |
p-value: 0.916Mixed Models Analysis
Primary
ROTEM EXTEM ML
Change in ROTEM parameter maximum lysis (ML) over 24 hours from Admission
Time frame: 0 (Admission), 1, 3, 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sham Remote Ischemic Conditioning | ROTEM EXTEM ML | Admission | 6 Percent |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM ML | 1 Hour | 5 Percent |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM ML | 3 Hour | 4 Percent |
| Sham Remote Ischemic Conditioning | ROTEM EXTEM ML | 24 Hour | 8 Percent |
| Remote Ischemic Conditioning | ROTEM EXTEM ML | 24 Hour | 7 Percent |
| Remote Ischemic Conditioning | ROTEM EXTEM ML | Admission | 6 Percent |
| Remote Ischemic Conditioning | ROTEM EXTEM ML | 3 Hour | 4 Percent |
| Remote Ischemic Conditioning | ROTEM EXTEM ML | 1 Hour | 4 Percent |
p-value: 0.085Mixed Models Analysis
Secondary
24 Hour Mortality
Secondary clinical outcomes
Time frame: up to 28 days or discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sham Remote Ischemic Conditioning | 24 Hour Mortality | 1 Participants |
| Remote Ischemic Conditioning | 24 Hour Mortality | 0 Participants |
p-value: 0.348Chi-squared
Secondary
28 Day Mortality
Secondary clinical outcomes
Time frame: up to 28 days or discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sham Remote Ischemic Conditioning | 28 Day Mortality | 1 Participants |
| Remote Ischemic Conditioning | 28 Day Mortality | 1 Participants |
p-value: 0.911Chi-squared
Secondary
Hospital Free Days
Secondary clinical outcomes
Time frame: up to 28 days or discharge
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sham Remote Ischemic Conditioning | Hospital Free Days | 24 Days |
| Remote Ischemic Conditioning | Hospital Free Days | 16 Days |
p-value: 0.151Wilcoxon (Mann-Whitney)
Secondary
ICU Free Days
Secondary clinical outcomes
Time frame: up to 28 days or discharge
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sham Remote Ischemic Conditioning | ICU Free Days | 27 Days |
| Remote Ischemic Conditioning | ICU Free Days | 25 Days |
p-value: 0.287Wilcoxon (Mann-Whitney)
Secondary
Nosocomial Infections
Secondary clinical outcomes
Time frame: up to 28 days or discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sham Remote Ischemic Conditioning | Nosocomial Infections | 5 Participants |
| Remote Ischemic Conditioning | Nosocomial Infections | 6 Participants |
p-value: 0.51Chi-squared
Secondary
Ventilator Free Days
Secondary clinical outcomes
Time frame: up to 28 days or discharge
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sham Remote Ischemic Conditioning | Ventilator Free Days | 27 Days |
| Remote Ischemic Conditioning | Ventilator Free Days | 26 Days |
p-value: 0.323Wilcoxon (Mann-Whitney)