The Effect of Remote Ischemic Preconditioning on Ischemia/Reperfusion Injury in a Liver Transplant Recipient

Overview

Ischemia and reperfusion injury is unavoidable during a liver transplantation. Remote ischemic preconditioning, a safe and feasible method, has previously been shown to reduce ischemia and reperfusion injury. In the transplantation setting, focus of remote ischemic preconditioning has been on the donor. However, preconditioning of the recipient may be a better approach due to the mechanisms by which ischemic preconditioning protects against ischemia and reperfusion injury. The aim of this randomised, double-blinded clinical trial is to biochemically assess the liver function after application of remote ischemic preconditioning on the recipient.

Full Title of Study: “The Effect of Remote Ischemic Preconditioning on Ischemia/Reperfusion Injury in a Liver Transplant Recipient (TRSPLNT) – A Randomized, Controlled, Double-blinded Clinical Trial.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Double (Investigator, Outcomes Assessor)
  • Study Primary Completion Date: June 2022

Detailed Description

Background The use of solid organ transplantation, including liver transplantation, is the golden standard for many end-stage solid organ diseases. Ischemia and reperfusion injury is unavoidable during a liver transplantation. Remote ischemic preconditioning, a safe and feasible method, has previously been shown to reduce ischemia and reperfusion injury. This may have a similar effect in a liver transplantation setting. In the transplantation setting, focus of remote ischemic preconditioning has been on the donor. However, preconditioning of the recipient may be a better approach due to the mechanisms by which ischemic preconditioning protects against ischemia and reperfusion injury. The aim of this randomised, double-blinded clinical trial is to biochemically assess the liver function after application of remote ischemic preconditioning on the recipient. Methods 52 patients undergoing a liver transplantation, included in accordance to the inclusion criteria, will be allocated to an intervention group (rIC-group) and compared to a retrospective non-intervention control group (non-rIC group) consisting of 52 patients. Patients in the non-intervention group will also be included in accordance to the inclusion criteria. Within two hours before surgery, patients in the intervention group will be subjected to four rounds of five-minute inflations and five-minute deflations of a pneumatic tourniquet applied on the right leg. Follow-up time will be 30 days. Measurements The aim of this trial is to assess the effect of remote ischemic preconditioning on the extent of liver injury and inflammation as a result of ischemia and reperfusion injury. Assessment will be done by measurement of biomarkers relevant to liver function and liver injury.

Interventions

  • Procedure: remote ischemic preconditioning (rIC)
    • Short intermittent peripheral occlusions and reperfusions of the blood flow in the right lower extremity with the help of a tourniquet.
  • Other: non remote ischemic preconditioning (non-rIC)
    • Retrospective group who have not undergone intervention.

Arms, Groups and Cohorts

  • Experimental: intervention group (rIC)
    • The rIC procedure will be applied on seated patients, who have been resting for at least five minutes. The active rIC procedure consists of four five-minute inflations of a pneumatic tourniquet to 100 mmHg above the patient’s systolic blood pressure separated by five-minute periods of complete deflation. Placement of the pneumatic tourniquet will be unilaterally on a lower limb (right thigh)
  • Other: control group (non-rIC)
    • The control group will be a retrospective group, who have undergone a liver transplantation and meet the inclusion criteria.

Clinical Trial Outcome Measures

Primary Measures

  • Post-operative change in ALT
    • Time Frame: Day 0-4
    • Extent of liver injury measured as change in ALT postoperative from day zero to day four .

Secondary Measures

  • Post-operative change in Aspartate Amonitransferase
    • Time Frame: Day 0-4
    • Serological markers of liver function
  • Post-operative change in Bilirubin
    • Time Frame: Day 0-4
    • Serological markers of liver function
  • Post-operative change in Alkaline Phosphatase
    • Time Frame: Day 0-4
    • Serological markers of liver function
  • Post-operative change in International Normalised Ratio
    • Time Frame: Day 0-4
    • Serological markers of liver function

Participating in This Clinical Trial

Inclusion Criteria

  • Patients undergoing liver transplantation – Patients aged 18 or above – Patients who have given an informed consent Exclusion Criteria:

  • Patients undergoing re-transplantation. – Patients who do not or cannot give an informed consent. – Patients who have undergone surgery six weeks prior to liver transplantation. – Patients with known peripheral vascular disease. – Patients with an infection localized to the area of rIC-intervention – Patients with at a high risk or with previous history of multiple thrombo-embolic diseases. – Patients undergoing active immunosuppressive therapy

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Rigshospitalet, Denmark
  • Provider of Information About this Clinical Study
    • Principal Investigator: Waqas Farooqui, MD, Principal Investigator – Rigshospitalet, Denmark
  • Overall Official(s)
    • Waqas Farooqui, MD, Principal Investigator, Doctor

References

Farooqui W, Pommergaard HC, Rasmussen A. Remote ischemic preconditioning of transplant recipients to reduce graft ischemia and reperfusion injuries: A systematic review. Transplant Rev (Orlando). 2018 Jan;32(1):10-15. doi: 10.1016/j.trre.2017.06.001. Epub 2017 Jun 15.

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