Clinical Trial: Effect of Remote Ischemic Conditioning on Trauma Patients With Hemorrhagic Shock

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Effect of Remote Ischemic Conditioning on Neutrophil Function and the Immune-Inflammatory and Coagulation Profiles in Trauma Patients With Hemorrhagic Shock

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 Summary: 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.
Sponsor: St. Michael's Hospital, Toronto

Current Primary Outcome:

  • Change in activation of polymorphonuclear neutrophil over 24 hours from baseline [ Time Frame: 0 (baseline), 1, 3, 24 hours ]
    • cell-surface expression of adhesion molecules (CD11b and CD62L), and oxidative burst activity (dihydrorhodamine)
    • assessed by flow cytometry using blood samples
  • Change in activation of endothelial cells over 24 hours from baseline [ Time Frame: 0 (baseline), 1, 3, 24 hours ]
    plasma levels of soluble adhesion molecules: E-selectin, P-selectin, ICAM-1, and VCAM.
  • Change in plasma levels of inflammatory mediators over 24 hours from baseline [ Time Frame: 0 (baseline), 1, 3, 24 hours ]
    plasma levels of cytokines: TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12, CRP, will be measured by multiplex assay.
  • Change in coagulation parameters over 24 hours from baseline [ Time Frame: 0 (baseline), 1, 3, 24 hours ]
    • INR, aPTT, platelet count
    • rotational thromboelastometry (ROTEM) parameters: coagulation time, clot formation time, α angle, clot firmness, fibrinogen polymerization, and clot lysis index
    • plasma levels of coagulation factors: D-dimers, Activated Protein C and tPA


Original Primary Outcome:

  • Change in activation of polymorphonuclear neutrophil over 24 hours from baseline [ Time Frame: 0 (baseline), 1, 8, 24 hours ]
    • cell-surface expression of adhesion molecules (CD11b and CD62L), degranulation markers (CD63 and CD66b), and oxidative burst activity (dihydrorhodamine)
    • assessed by flow cytometry using blood samples
  • Change in activation of endothelial cells over 24 hours from baseline [ Time Frame: 0 (baseline), 1, 8, 24 hours ]
    plasma levels of soluble adhesion molecules: E-selectin, P-selectin, ICAM-1, and VCAM.
  • Change in plasma levels of inflammatory mediators over 24 hours from baseline [ Time Frame: 0 (baseline), 1, 8, 24 hours ]
    plasma levels of cytokines: TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12, CRP, will be measured by multiplex assay.
  • Change in coagulation parameters over 24 hours from baseline [ Time Frame: 0 (baseline), 1, 8, 24 hours ]
    • INR, aPTT, platelet count
    • rotational thromboelastometry (ROTEM) parameters: coagulation time, clot formation time, α angle, clot firmness, fibrinogen polymerization, and clot lysis index
    • plasma levels of coagulation factors: D-dimers, Activated Protein C and tPA


Current Secondary Outcome: Follow up data after 24 hours [ Time Frame: up to 28 days or discharge ]

Patients will be followed during the course of their hospital stay up to 28 days or discharge, recording any new surgical procedure, including tracheostomy, duration of mechanical ventilation, development of sepsis or a new organ failure, length of ICU and hospital stay.


Original Secondary Outcome: Same as current

Information By: St. Michael's Hospital, Toronto

Dates:
Date Received: February 18, 2014
Date Started: May 2015
Date Completion: May 2017
Last Updated: January 5, 2017
Last Verified: January 2017