Effect of Remote Ischemic Conditioning on Trauma Patients With Hemorrhagic Shock

NCT02071290 | Completed Results

• 1 other identifier: SMH-RIC-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemorrhagic Shock

Keywords

Hemorrhagic Shock; Remote Ischemic Conditioning

Outcome Measures

Primary Outcomes (19)

• 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.

  0 (Admission), 1, 3, and 24 hours after intervention

• 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.

  0 (Admission), 1, 3, and 24 hours after intervention

• 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.

  0 (Admission), 1, 3, 24 hours after intervention

• 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.

  0 (Admission), 1, 3, and 24 hours after intervention

• Endothelial Injury (Heparan Sulfate)

  Change in plasma levels of endothelial injury marker Heparan Sulfate over 24 hours from Admission

  0 (Admission), 1, 3, and 24 hours after intervention

• Endothelial Injury (Hyaluronan)

  Change in plasma levels of endothelial injury marker Hyaluronan over 24 hours from Admission

  0 (Admission), 1, 3, 24 hours

• Endothelial Injury (Syndecan-1)

  Change in plasma levels of endothelial injury marker Syndecan-1 over 24 hours from Admission

  0 (Admission), 1, 3, and 24 hours after intervention

• Plasma TNF-α

  Change in plasma levels of inflammatory mediator TNF-α over 24 hours from Admission

  0 (Admission), 1, 3, and 24 hours after intervention

• Plasma IL-6

  Change in plasma levels of inflammatory mediator IL-6 over 24 hours from Admission

  0 (Admission), 1, 3, 24 hours

• Plasma IL-8

  Change in plasma levels of inflammatory mediator IL-8 over 24 hours from Admission

  0 (Admission), 1, 3, 24 hours

• Plasma IL-10

  Change in plasma levels of anti-inflammatory mediator IL-10 over 24 hours from Admission

  0 (Admission), 1, 3, 24 hours

• ROTEM EXTEM CT

  Change in ROTEM parameter Clotting Time (CT) over 24 hours from Admission

  0 (Admission), 1, 3, 24 hours

• ROTEM EXTEM CFT

  Change in ROTEM parameter Clot Formation Time (CFT) over 24 hours from Admission

  0 (Admission), 1, 3, 24 hours

• ROTEM EXTEM A10

  Change in ROTEM parameter A10 over 24 hours from Admission

  0 (Admission), 1, 3, 24 hours

• ROTEM EXTEM Alpha Angle

  Change in ROTEM parameter Alpha Angle over 24 hours from Admission

  0 (Admission), 1, 3, 24 hours

• ROTEM EXTEM ML

  Change in ROTEM parameter maximum lysis (ML) over 24 hours from Admission

  0 (Admission), 1, 3, 24 hours

• Plasma D-Dimer

  Change in plasma D-Dimer levels over 24 hours from Admission

  0 (Admission), 1, 3, 24 hours

• Plasma Protein C

  Change in plasma Protein C levels over 24 hours from Admission

  0 (Admission), 1, 3, 24 hours

• Plasma Fibrinogen

  Change in plasma fibrinogen levels over 24 hours from Admission

  0 (Admission), 1, 3, 24 hours

Secondary Outcomes (6)

• Ventilator Free Days

  up to 28 days or discharge

• ICU Free Days

  up to 28 days or discharge

• Hospital Free Days

  up to 28 days or discharge

• Nosocomial Infections

  up to 28 days or discharge

• 24 Hour Mortality

  up to 28 days or discharge

Study Arms (2)

Sham Remote Ischemic Conditioning

SHAM COMPARATOR

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

Device: Pneumatic tourniquet

Remote Ischemic Conditioning

EXPERIMENTAL

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

Device: Pneumatic tourniquet

Interventions

Pneumatic tourniquet DEVICE

Four cycles of brief occlusion of bloodflow to the thigh (5 minutes) followed by reperfusion (5 minutes) using a pneumatic tourniquet Remote Ischemic Conditioning

Remote Ischemic Conditioning; Sham Remote Ischemic Conditioning

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B1W8, Canada

Location

Related Publications (1)

• Leung CH, Rizoli SB, Trypcic S, Rhind SG, Battista AP, Ailenberg M, Rotstein OD. Effect of remote ischemic conditioning on the immune-inflammatory profile in patients with traumatic hemorrhagic shock in a randomized controlled trial. Sci Rep. 2023 Apr 29;13(1):7025. doi: 10.1038/s41598-023-33681-3.

  PMID: 37120600 DERIVED

MeSH Terms

Conditions

Shock, Hemorrhagic

Condition Hierarchy (Ancestors)

Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Limitations and Caveats

Prolonged EMS transport time, transfers, and clinical procedures contributed to delayed application and completion of RIC, resulting in several patients exceeding the 4-hour inclusion criteria and were therefore excluded due to protocol violation.

Results Point of Contact

• Title: Dr. Ori Rotstein
• Organization: St. Michael's Hospital

rotsteino@smh.ca

416-864-6060

Study Officials

• Ori D Rotstein, MD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2014
• First Posted: February 25, 2014
• Study Start: May 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: June 7, 2023
• Results First Posted: March 27, 2019

Record last verified: 2023-05

Locations

CA (1)