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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Liver Transplant; Complications; Ischemia Reperfusion Injury
• Intervention / Treatment: Procedure: remote ischemic preconditioning (rIC); Other: non remote ischemic preconditioning (non-rIC)

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.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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)	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: control group (non-rIC); The control group will be a retrospective group, who have undergone a liver transplantation and meet the inclusion criteria.	Other: non remote ischemic preconditioning (non-rIC); Retrospective group who have not undergone intervention.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complication rate	Rate of post-operative complications	Follow-up on day 30
Days in ICU (Intensive Care Unit)	Length of post-operative stay in ICU	Follow-up on day 30
Total length of hospital-stay		Follow-up on day 30

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Waqas Farooqui, MD, Doctor

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2020
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: November 25, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (Actual): November 29, 2018

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 5, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: liver transplantation; remote ischemic preconditioning; ischemia reperfusion injury
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Ischemia; Wounds and Injuries; Reperfusion Injury
• Other Study ID Numbers: TRSPLNT001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No