Methylprednisolone N Acetylcysteine in Hepatic Resections

• Status: Terminated
• Trial end date: 2013-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a prospective double-blind randomized phase II clinical trial, with two groups of intervention (one with administration of N-acetylcysteine and the other with administration of methylprednisolone), and one group of placebo. The purpose of this study is to investigate the role of N-acetylcysteine and Methylprednisolone in the modulation of warm ischemia of the liver during hepatic resection. In fact to avoid massive blood loss in liver surgery, continuous or intermittent vascular clamping of the hepatic hilum ('Pringle maneuver') is generally used with good results. However, as a consequence, ischemia and subsequent reperfusion result in complex metabolic, immunological, and microvascular changes, which together might contribute to hepatocellular damage and dysfunction. This phenomenon, known as ischemia-reperfusion (IR) injury of the liver, is a complex multi-path process leading to the activation of some inflammatory pathways. Any patient candidate to liver resection will be enrolled in the study based on the aforementioned criteria. The primary objective of the study is to assess the real efficacy of Methylprednisolone and N-acetylcysteine in reducing the secondary damage from ischemia reperfusion injury in liver resection and in reducing inflammatory response. Secondary objective of the study is whether the reduction of ischemia-reperfusion injury results in: lower incidence of postoperative liver failure, improvement of postoperative liver function, and reduction of blood components transfusions. The randomization will be done the day before the operation. The drugs will be prepared in a blind fashion by the hospital pharmacy. The hospital pharmacy will provide to each patient a drip to make bolus of about an hour before the start of the liver resection and a syringe pump for an infusion of approximately 6 hours. If the patient is enrolled and randomized in the placebo arm, he/she will receive 250 ml of glucose 5% plus the infusion of 100 ml of glucose 5% If the patient is randomized in the Methylprednisolone arm, he/she will receive a dose of 500 mg in 250 ml of glucose 5% plus 100 mg of glucose 5%. If the patient is randomized in the N-acetylcysteine arm, he/she will receive a dose of 150 mg/kg in 250 ml of glucose 5% plus N-acetylcysteine 50 mg/kg in 100 ml glucose 5%. Systematic sampling of liver function tests will be done the day before the operation, at the end of the operation, as well as in postoperative day 1, 3, 5 and 7.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Istituto Clinico Humanitas
• Treatments: Acetylcysteine; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; N-monoacetylcystine; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Criteria

Inclusion Criteria:

• Any sex, any race, any ethnicity

• Age > 18

• Primary and secondary liver tumors

• Normal renal function

• Anticipated Pringle's length > 30 minutes

Exclusion Criteria:

• Renal failure of any grade

• ASA 4

• Associate major surgery

• Intraoperative bleeding > 1500 ml

• Allergy to N-acetylcysteine or Methylprednisolone