Hepatocellular Cancer
Conditions
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.
Interventions
DEVICEActive RIC
DEVICESham Control
Sponsors
Duke-NUS Graduate Medical School
Singapore General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| serum ALT (unit/L) following liver resection, measured at 24 hours | 24 hours | serum ALT as a measure of acute liver injury |
| serum AST (unit/L) following liver resection, measured at 24 hours | 24 hours | serum AST as a measure of acute liver injury |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| serum ALT (unit/L) following liver resection, measured at 2 weeks | 2 weeks | serum ALT 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 |
| 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 |
| 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 |
| 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 |
| Rate of hospital admission | 30 days | Rate of hospital admission |
| Mortality | 30 days | Mortality |
| 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 |
| serum ALT (unit/L) following liver resection, measured at 48 hours | 48 hours | serum ALT as a measure of acute liver injury |
Countries
Singapore
Contacts
Primary ContactJin Yao Teo
Outcome results
None listed