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

NCT02710266 | Terminated Phase 3

• 1 other identifier: 4-2011-0936
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Disease

Keywords

Synthetic Protease Inhibitor; Hepatectomy; Postoperative Complications

Outcome Measures

Primary Outcomes (1)

• Postoperative complications

  Within the first 30 days after surgery

Secondary Outcomes (2)

• Liver function recovery time

  4 weeks

• length of hospitalization

  4 weeks

Study Arms (3)

Placebo group

PLACEBO COMPARATOR

hepatectomy without Gabexate Mesilate

Drug: hepatectomy with dextrose water

Preoperative Gabexate Mesilate group

EXPERIMENTAL

Gabexate Mesilate administered from the preoperative day

Drug: Preoperative Gabexate Mesilate group

Intraoperative Gabexate Mesilate group

EXPERIMENTAL

Gabexate Mesilate administered from the operative day

Drug: Intraoperative Gabexate Mesilate group

Interventions

Preoperative Gabexate Mesilate group DRUG

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.

Preoperative Gabexate Mesilate group

Intraoperative Gabexate Mesilate group DRUG

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.

Intraoperative Gabexate Mesilate group

hepatectomy with dextrose water DRUG

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

Placebo group

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Severance Hospital

Seoul, 03722, South Korea

Location

Related Publications (1)

• Kim YI, Fujita S, Hwang YJ, Chun JM, Song KE, Chun BY. Successful intermittent application of the Pringle maneuver for 30 minutes during human hepatectomy: a clinical randomized study with use of a protease inhibitor. Hepatogastroenterology. 2007 Oct-Nov;54(79):2055-60.

  PMID: 18251159 BACKGROUND

MeSH Terms

Conditions

Liver Diseases; Postoperative Complications

Interventions

Hepatectomy

Condition Hierarchy (Ancestors)

Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Digestive System Surgical Procedures; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2016
• First Posted: March 16, 2016
• Study Start: February 24, 2012
• Primary Completion: February 25, 2017
• Study Completion: February 25, 2017
• Last Updated: July 18, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)