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

Hepatocellular Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03594929
• Other study ID #: The ERIC-LIVER trial
• Status: Recruiting
• Phase: N/A
• Start date: August 15, 2016
• Est. completion date: April 1, 2019

Study information

• Verified date: July 2018
• Source: Singapore General Hospital
• Contact: Jin Yao Teo
• Phone: 63214515
• Email: teo.jin.yao[@]singhealth.com.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: April 1, 2019
• Est. primary completion date: January 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Cancer
• Liver Neoplasms

Intervention

Device:
• Active RIC

• Sham Control

Locations

Country	Name	City	State
Singapore	Singapore General Hospital	Singapore

Sponsors (2)

Lead Sponsor	Collaborator
Singapore General Hospital	Duke-NUS Graduate Medical School

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	serum ALT (unit/L) following liver resection, measured at 24 hours	serum ALT as a measure of acute liver injury	24 hours
Primary	serum AST (unit/L) following liver resection, measured at 24 hours	serum AST as a measure of acute liver injury	24 hours
Secondary	serum ALT (unit/L) following liver resection, measured at 6 hours	serum ALT as a measure of acute liver injury	6 hours
Secondary	serum ALT (unit/L) following liver resection, measured at 48 hours	serum ALT as a measure of acute liver injury	48 hours
Secondary	serum ALT (unit/L) following liver resection, measured at 2 weeks	serum ALT as a measure of acute liver injury	2 weeks
Secondary	serum AST (unit/L) following liver resection, measured at 6 hours	serum AST as a measure of acute liver injury	6 hours
Secondary	serum AST (unit/L) following liver resection, measured at 48 hours	serum AST as a measure of acute liver injury	48 hours
Secondary	serum ALT (unit/L) following liver resection, measured at 2 weeks	serum AST as a measure of acute liver injury	2 weeks
Secondary	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.
Secondary	Acute liver ischemia reperfusion injury on histology	Assessed by checking liver histology of the resected specimen	up to 2 weeks
Secondary	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
Secondary	Episodes of culture-confirmed sepsis	Episodes of culture-confirmed sepsis	30 days
Secondary	Serum creatine (umol/L)	Measure of acute kidney injury based on rise in serum creatine on day 3 post op	3 days
Secondary	ITU and hospital stay	ITU and hospital stay	Up to 30 days
Secondary	Rate of hospital admission	Rate of hospital admission	30 days
Secondary	Mortality	Mortality	30 days