Liver Protection of RIPC in Pediatric Living Donor Liver Transplantation

Study Overview
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Brief Summary
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Remote ischemic preconditioning(RIPC) is emerging as an promising therapeutic paradigm to combat the detrimental impact of ischemic and reperfusion injury. In liver transplantation, ischemic and reperfusion injury severely impacts the post-surgery liver function and patient outcome. This prospective, double blind, randomized clinical trial is aimed to test the protective effect of RIPC against hepatic ischemic and reperfusion injury in pediatric liver transplantation.

Detailed Description
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Pediatric liver transplantation remains the major therapeutic strategy for pediatric biliary atresia patients. With almost 60 years of improvements and refinements in surgical techniques and perioperative management standards, liver transplantation is gaining popularity and gradually turns out to be the only curative treatment option for patients with irrevocable liver failure, such as childhood acute or chronic liver failure, inherited liver diseases and also biliary atresia. In liver transplantation, hepatic ischemic and reperfusion injury (HIRI) remains to be a critical clinical issue. Importantly, it is well known that the severity of HIRI may have fundamental impact on the transplanted organ function and long term graft survival. Furthermore, pediatric patients are more venerable and less tolerated to receive an ischemic donor liver due to their small body weight.Although detrimental impact of HIPI on graft function has long been recognized, little progress has been made to attenuate the severity of the HIPI compared to cardiac ischemic and reperfusion (IR) injury. In experimental animal models, remote ischemic preconditioning has been consistently shown to have beneficial effects. However, this protective paradigm has yet not been tested in liver transplantation patients in clinical scenario. Considering the growing number of pediatric patients undergoing liver transplantation and their possibly underdeveloped organ function, the investigators sought to determine whether remote ischemic preconditioning could ameliorate HIPI and improve long term graft/patient survival in pediatric liver transplantation patients using this double-blind randomized clinical trial.

Official Title
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Remote Ischemic Preconditioning Protects Against Hepatic Ischemic and Reperfusion Injury in Pediatric Living Donor Liver Transplantation

Conditions
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Hepatic Ischemic and Reperfusion Injury

Intervention / Treatment
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* Device: remote ischemic preconditioning(RIPC)
* Device: Sham RIPC


Participation Criteria
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Eligibility Criteria
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The inclusion criteria were as follows: American society of anesthesiologists score of I-III; age of 3-72 months elective living LT surgery. The exclusion criteria were as follows: peripheral vascular disease; history of thromboembolism; systemic or local infection before surgery; autoimmune diseases; severe congenital heart disease history of LT.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DR-RIPC (donor and recipient RIPC group)<br>Both donors and recipients receive remote ischemic preconditioning, with three 5-min cycles of remote limb ischemia, which was induced by an automated cuff-inflator placed on the right upper arm(donor) or right lower limb(recipient) and inflated to 15 mmHg above systolic pressure, with an intervening 5 min of reperfusion during which the cuff was deflated. | Device: remote ischemic preconditioning(RIPC)<br>* After anesthesia induction, donors or recipients will be treated with automated blood pressure cuffs on their upper arms to receive RIPC by cuff inflation (to 15mmHg above systolic pressure) for 5 minutes and left inflated for 5 minutes. The cuff will then be deflated to 0 mm Hg and left uninflated for 5 minutes. This cycle will be performed 3 times in total.<br>|
| Sham Comparator: S-RIPC (sham RIPC)<br>Patients had a deflated cuff placed on the right upper arm or right lower limb for 30 min | Device: Sham RIPC<br>* Only blood pressure cuff will be placed to the patient, but no inflation or deflation will be performed.<br>|
| Experimental: R-RIPC (recipient RIPC group)<br>Recipients receive remote ischemic preconditioning, with three 5-min cycles of remote limb ischemia, which was induced by an automated cuff-inflator placed on the right lower limb and inflated to 15 mmHg above systolic pressure, with an intervening 5 min of reperfusion during which the cuff was deflated. | Device: remote ischemic preconditioning(RIPC)<br>* After anesthesia induction, donors or recipients will be treated with automated blood pressure cuffs on their upper arms to receive RIPC by cuff inflation (to 15mmHg above systolic pressure) for 5 minutes and left inflated for 5 minutes. The cuff will then be deflated to 0 mm Hg and left uninflated for 5 minutes. This cycle will be performed 3 times in total.<br>|
| Experimental: D-RIPC (donor RIPC group)<br>Donors receive remote ischemic preconditioning, with three 5-min cycles of remote limb ischemia, which was induced by an automated cuff-inflator placed on the right upper arm and inflated to 15 mmHg above systolic pressure, with an intervening 5 min of reperfusion during which the cuff was deflated. | Device: remote ischemic preconditioning(RIPC)<br>* After anesthesia induction, donors or recipients will be treated with automated blood pressure cuffs on their upper arms to receive RIPC by cuff inflation (to 15mmHg above systolic pressure) for 5 minutes and left inflated for 5 minutes. The cuff will then be deflated to 0 mm Hg and left uninflated for 5 minutes. This cycle will be performed 3 times in total.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative maximum AST | Postoperative maximum aspartate transaminase (AST) | Postoperative 0-7 day | 
| Postoperative maximum ALT | Postoperative maximum alanine transaminase (ALT) | Postoperative 0-7 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of early graft dysfunction(EAD) | occurrence of early graft dysfunction | 7 days after surgery | 
| Number of recipients with primary nonfunction | Number of recipients with primary nonfunction | 7 days after surgery | 
| Number of recipients/donors with postoperative complications | Number of recipients/donors with postoperative complications | 7 days after surgery | 
| The overall survival of recipients | 1-year and 3-year overall survival of recipients after liver transplantation | 1-year and 3-year overall survival of recipients | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RIPC, hepatic ischemic and reperfusion injury, pediatric living donor liver transplantation