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

Phase 3

Terminated

• Conditions: Liver Disease
• Interventions: Drug: hepatectomy with dextrose water; Drug: Preoperative Gabexate Mesilate group; Drug: Intraoperative Gabexate Mesilate group

• Registration Number: NCT02710266
• Lead Sponsor: Yonsei University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-02-24
• Study First Submitted: 2016-02-01
• Study First Submitted QC: 2016-03-11
• Study First Posted: 2016-03-16
• Primary Completion: 2017-02-25
• Study Completion: 2017-02-25
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-15
• Last Update Posted: 2018-07-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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

Read More

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.)

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo group	hepatectomy with dextrose water	hepatectomy without Gabexate Mesilate
Preoperative Gabexate Mesilate group	Preoperative Gabexate Mesilate group	Gabexate Mesilate administered from the preoperative day
Intraoperative Gabexate Mesilate group	Intraoperative Gabexate Mesilate group	Gabexate Mesilate administered from the operative day

Primary Outcome Measures

Name	Time	Method
Postoperative complications	Within the first 30 days after surgery

Secondary Outcome Measures

Name	Time	Method
Liver function recovery time	4 weeks
length of hospitalization	4 weeks

Trial Locations

Locations (1)

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of