Effect of Remote Ischaemic preConditioning on Liver Injury in Patients Undergoing LIVER Resection Surgery

Study Overview
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Brief Summary
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Liver resection has improved health outcomes in patients with hepatocellular carcinoma (HCC) in Singapore and worldwide. However, due to acute ischaemia/reperfusion injury (IRI) to the liver at the time of surgery, patients still experience significant morbidity and mortality. Therefore, novel therapies are required to protect the liver against acute IRI during partial hepatectomy. Remote ischaemic conditioning (RIC) using transient limb ischaemia/reperfusion has been shown to protect the liver in experimental animal studies. In the ERIC-LIVER trial the investigators investigate whether RIC can reduce liver injury and preserve liver function in patients with HCC undergoing partial hepatectomy.

Detailed Description
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Liver resection has improved health outcomes in patients with hepatocellular carcinoma (HCC) in Singapore and worldwide. However, due to acute ischaemia/reperfusion injury (IRI) to the liver at the time of surgery, patients still experience significant morbidity and mortality. Therefore, novel therapies are required to protect the liver against acute IRI during partial hepatectomy. Remote ischaemic conditioning (RIC) using transient limb ischaemia/reperfusion has been shown to protect the liver in experimental animal studies. In the ERIC-LIVER trial the investigators investigate whether RIC can reduce liver injury and preserve liver function in patients with HCC undergoing partial hepatectomy. 50 patients with HCC undergoing partial hepatectomy will be randomised to receive either RIC (four-5 minute arm cuff inflations/deflations) or sham control (four-5 minute arm cuff simulated inflations/deflations) after induction of anesthesia and prior to surgical incision. The primary endpoint of the study will be acute liver injury assessed by serum transaminases measured at 24 hours post-resection. Secondary endpoints will include liver function in subset of patients (N=24, assessed by indocyanine green [ICG] clearance measured at 24 hours post-resection), incid ence of liver failure, episodes of confirmed sepsis, acute kidney injury, intensive care unit and hospital stay, and quality of life.

Official Title
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Effect of Remote Ischaemic preConditioning on Liver Injury in Patients Undergoing LIVER Resection Surgery: The ERIC-LIVER Trial

Conditions
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Hepatocellular Cancer

Intervention / Treatment
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* Device: Active RIC
* Device: Sham Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 21 years and above Patients undergoing partial hepatectomy for primary HC Exclusion Criteria: Patients with significant pulmonary disease (FEV1<40% predicted). Patients with known severe renal failure with a GFR<30 mL/min/1.73 m2. Patients on sulphonylurea or nicorandil, as these medications may interfere with the protective effect of RIC. Patients recruited into another study which may impact on this study. Significant peripheral arterial disease affecting the upper limbs. Patients undergoing repeat liver resection surgery.

Ages Eligible for Study
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Minimum Age: 21 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active RIC<br>Active RIC using a manual BP cuff to inflate to 200mmHg. | Device: Active RIC<br> <br> |
| Sham Comparator: Sham Control<br>A sham control using a manual blood pressure cuff visually identical to that used in the RIC protocol will be placed on the upper arm and a simulated RIC protocol will be administered. | Device: Sham Control<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum ALT (unit/L) following liver resection, measured at 24 hours | serum ALT as a measure of acute liver injury | 24 hours | 
| serum AST (unit/L) following liver resection, measured at 24 hours | serum AST as a measure of acute liver injury | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum ALT (unit/L) following liver resection, measured at 6 hours | serum ALT as a measure of acute liver injury | 6 hours | 
| serum ALT (unit/L) following liver resection, measured at 48 hours | serum ALT as a measure of acute liver injury | 48 hours | 
| serum ALT (unit/L) following liver resection, measured at 2 weeks | serum ALT as a measure of acute liver injury | 2 weeks | 
| serum AST (unit/L) following liver resection, measured at 6 hours | serum AST as a measure of acute liver injury | 6 hours | 
| serum AST (unit/L) following liver resection, measured at 48 hours | serum AST as a measure of acute liver injury | 48 hours | 
| serum ALT (unit/L) following liver resection, measured at 2 weeks | serum AST as a measure of acute liver injury | 2 weeks | 
| Indocyanine Green (ICG) retention test. | Liver function as assessed by the ICG retention test. Testing is optional | baseline in pre-admission clinic and post-operation day 1. | 
| Acute liver ischemia reperfusion injury on histology | Assessed by checking liver histology of the resected specimen | up to 2 weeks | 
| presence/absence of liver failure based on serum bilirubin and INR on post op day 5 | serum bilirubin and INR on post op day 5 | Baseline and day 5 post-surgery | 
| Episodes of culture-confirmed sepsis | Episodes of culture-confirmed sepsis | 30 days | 
| Serum creatine (umol/L) | Measure of acute kidney injury based on rise in serum creatine on day 3 post op | 3 days | 
| ITU and hospital stay | ITU and hospital stay | Up to 30 days | 
| Rate of hospital admission | Rate of hospital admission | 30 days | 
| Mortality | Mortality | 30 days |