Evaluation of the Effect of Gabexate Mesilate in the Hepatocyte Protection After Liver Resection

Sponsor

Yonsei University (Other)

Overall Status

Terminated

CT.gov ID

NCT02710266

Collaborator

(none)

Enrollment

Location

Arms

60.1

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Liver resection have been a primary treatment option for lesions found in the liver. With improvements in surgical technique and perioperative patient management, morbidity and mortality related to liver resection have been greatly reduced. However, many patients with hepatocellular carcinoma have underlying liver disease. Severity of underlying liver disease plays an important role in decision making of resection extent. Therefore, liver failure and decreased liver function following liver resection still remains to be an critical issue.

Postresection liver failure is generally defined by serum total bilirubin greater than 3mg/dL and prothrombin time of less than 50% of normal (INR >1.7). Pathophysiology of postresection liver failure is not yet well known. However, sepsis after liver resection, small-for-size syndrome (SFSS), and ischemia/reperfusion injury are known to have important roles in persistant liver injury after resection.

After a liver resection, kupffer cells are drastically decreased and innate immunity of the patient is also damaged. This process causes the patient to be vulnerable to infection. In addition, with continuous endotoxin secretion, dysfunction in kupffer cells are triggered and liver regeneration is affected.

Complex mechanisms leading to dysfunctional kupffer cells and apoptosis and necrosis of hepatocytes are mediated by neutrophils, complement, reactive oxygen species, and acute inflammatory cytokines.

Recent studies have reported on many promising effects of the synthetic protease inhibitor, such as Gabexate mesilate. These include antioxidant effect, inhibition of acute inflammatory cytokine reaction, and anticoagulatory property. Based on these effects, synthetic protease inhibitor have gained attention in the role of hepatocyte protection after liver resection.

Currently, there is a report on the hepatocyte protective effects of Gabexate Mesilate on ischemia/reperfusion injury caused by the Pringle maneuver. However, with the advances in surgical technique and equipment, many surgeons now perform liver resection without Pringle maneuver. Therefore, this study was designed to determine effects of Gabexate Mesilate in the liver resection performed without Pringle maneuver.

Condition or Disease	Intervention/Treatment	Phase
Liver Disease	Drug: Preoperative Gabexate Mesilate group Drug: Intraoperative Gabexate Mesilate group Drug: hepatectomy with dextrose water	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Supportive Care

Actual Study Start Date :

Feb 24, 2012

Actual Primary Completion Date :

Feb 25, 2017

Actual Study Completion Date :

Feb 25, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo group hepatectomy without Gabexate Mesilate	Drug: hepatectomy with dextrose water Gabexate Mesilate is not administered. As placebo, 500cc of 5% dextrose water is administered at 40cc/hr for 12 hours
Experimental: Preoperative Gabexate Mesilate group Gabexate Mesilate administered from the preoperative day	Drug: Preoperative Gabexate Mesilate group Gabexate Mesilate is administered from the preoperative day and continued for 5 days. 300mg of Gabexate Mesilate is mixed with 500cc of 5% dextrose water and administered at 40cc/hr for 12 hours each day.
Experimental: Intraoperative Gabexate Mesilate group Gabexate Mesilate administered from the operative day	Drug: Intraoperative Gabexate Mesilate group Gabexate Mesilate is administered from the operative day and continued for 5 days. 300mg of Gabexate Mesilate is mixed with 500cc of 5% dextrose water and administered at 40cc/hr for 12 hours each day.

Arm

Intervention/Treatment

Placebo Comparator: Placebo group

hepatectomy without Gabexate Mesilate

Drug: hepatectomy with dextrose water

Gabexate Mesilate is not administered. As placebo, 500cc of 5% dextrose water is administered at 40cc/hr for 12 hours

Experimental: Preoperative Gabexate Mesilate group

Gabexate Mesilate administered from the preoperative day

Drug: Preoperative Gabexate Mesilate group

Gabexate Mesilate is administered from the preoperative day and continued for 5 days. 300mg of Gabexate Mesilate is mixed with 500cc of 5% dextrose water and administered at 40cc/hr for 12 hours each day.

Experimental: Intraoperative Gabexate Mesilate group

Gabexate Mesilate administered from the operative day

Drug: Intraoperative Gabexate Mesilate group

Gabexate Mesilate is administered from the operative day and continued for 5 days. 300mg of Gabexate Mesilate is mixed with 500cc of 5% dextrose water and administered at 40cc/hr for 12 hours each day.

Outcome Measures

Primary Outcome Measures

Postoperative complications [Within the first 30 days after surgery]

Secondary Outcome Measures

Liver function recovery time [4 weeks]
length of hospitalization [4 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All liver tumors that require resection of more than two segments of the liver.
Age ≥20 and ≤80
General performance status: the Karnofsky score> 70% or ECOG 0-1

Exclusion Criteria:

Hepatic duct reconstruction was performed
ASA (American society of anesthesiologists' physical status classification) score: ≥3
Patients with drug or alcohol addiction
Patients showing low compliance
Patients who not want to involve the clinical trial
Patients who are unable to read or understand the informed consent, sign a consent form (eg, mental retardation, blindness, illiteracy, foreign, etc.)