Clinical trial NCT02710266: Evaluation of the Effect of Gabexate Mesilate in the Hepatocyte Protection After Liver Resection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Liver Disease
Keywords: Synthetic Protease Inhibitor
Hepatectomy
Postoperative Complications
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2016-03-16
Enrollment: 2
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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.)

Primary outcomes:
measure: Postoperative complications
timeFrame: Within the first 30 days after surgery
Secondary outcomes:
measure: Liver function recovery time
timeFrame: 4 weeks
measure: length of hospitalization
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
Study officials:
References:
citation: 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.