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

Not Applicable

• Conditions: Hepatocellular Cancer
• Interventions: Device: Active RIC; Device: Sham Control

• Registration Number: NCT03594929
• Lead Sponsor: Singapore General Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-08-15
• Study First Submitted: 2018-04-19
• Status Verified: 2018-07
• Study First Submitted QC: 2018-07-19
• Last Update Submitted: 2018-07-19
• Study First Posted: 2018-07-20
• Last Update Posted: 2018-07-20
• Primary Completion: 2019-01-18
• Study Completion: 2019-04-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active RIC	Active RIC	Active RIC using a manual BP cuff to inflate to 200mmHg.
Sham Control	Sham Control	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.

Primary Outcome Measures

Name	Time	Method
serum AST (unit/L) following liver resection, measured at 24 hours	24 hours	serum AST as a measure of acute liver injury
serum ALT (unit/L) following liver resection, measured at 24 hours	24 hours	serum ALT as a measure of acute liver injury

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Singapore General Hospital; 🇸🇬 Singapore, Singapore