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

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

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.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Cancer
• Intervention / Treatment: Device: Active RIC; Device: Sham Control

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jin Yao Teo; Phone Number: 63214515; Email: teo.jin.yao@singhealth.com.sg

Study Locations

• Singapore
  • Singapore, Singapore, 169608
    • Recruiting
    • Singapore General Hospital
    • Contact: Jin Yao Teo; Phone Number: 63214515; Email: teo.jin.yao@singhealth.com.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active RIC; Active RIC using a manual BP cuff to inflate to 200mmHg.	Device: Active RIC
SHAM_COMPARATOR: 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.	Device: Sham Control

What is the study measuring?

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
Mortality	Mortality	30 days
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

Collaborators and Investigators

• Sponsor: Singapore General Hospital
• Collaborators: Duke-NUS Graduate Medical School

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 15, 2016
• Primary Completion (ANTICIPATED): January 18, 2019
• Study Completion (ANTICIPATED): April 1, 2019

Study Registration Dates

• First Submitted: April 19, 2018
• First Submitted That Met QC Criteria: July 19, 2018
• First Posted (ACTUAL): July 20, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 20, 2018
• Last Update Submitted That Met QC Criteria: July 19, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Carcinoma, Hepatocellular; Liver Neoplasms
• Other Study ID Numbers: The ERIC-LIVER trial

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