Clinical trial NCT03594929: Effect of Remote Ischaemic preConditioning on Liver Injury in Patients Undergoing LIVER Resection Surgery
Official title: Effect of Remote Ischaemic preConditioning on Liver Injury in Patients Undergoing LIVER Resection Surgery: The ERIC-LIVER Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hepatocellular Cancer
Lead sponsor: Singapore General Hospital
Sponsor class: OTHER
Collaborators: name: Duke-NUS Graduate Medical School
First posted: 2018-07-20
Enrollment: 50
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: serum ALT (unit/L) following liver resection, measured at 24 hours
timeFrame: 24 hours
measure: serum AST (unit/L) following liver resection, measured at 24 hours
timeFrame: 24 hours
Secondary outcomes:
measure: serum ALT (unit/L) following liver resection, measured at 6 hours
timeFrame: 6 hours
measure: serum ALT (unit/L) following liver resection, measured at 48 hours
timeFrame: 48 hours
measure: serum ALT (unit/L) following liver resection, measured at 2 weeks
timeFrame: 2 weeks
measure: serum AST (unit/L) following liver resection, measured at 6 hours
timeFrame: 6 hours
measure: serum AST (unit/L) following liver resection, measured at 48 hours
timeFrame: 48 hours
measure: serum ALT (unit/L) following liver resection, measured at 2 weeks
timeFrame: 2 weeks
measure: Indocyanine Green (ICG) retention test.
timeFrame: baseline in pre-admission clinic and post-operation day 1.
measure: Acute liver ischemia reperfusion injury on histology
timeFrame: up to 2 weeks
measure: presence/absence of liver failure based on serum bilirubin and INR on post op day 5
timeFrame: Baseline and day 5 post-surgery
measure: Episodes of culture-confirmed sepsis
timeFrame: 30 days
measure: Serum creatine (umol/L)
timeFrame: 3 days
measure: ITU and hospital stay
timeFrame: Up to 30 days
measure: Rate of hospital admission
timeFrame: 30 days
measure: Mortality
timeFrame: 30 days
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Singapore General Hospital
Study officials:
References: