Study of the Protective Effect of Mechanism of Pentoxyfilline After Major Liver Resection Under Inflow Occlusion (Pringle Manoeuvre)

The investigators hypothecate that pentoxyfilline increase significantly the liver regeneration and reduces significantly ischemia and reperfusion (I/R) injury in major liver using aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as marker of I/R injury.

Study Overview

• Status: Completed
• Conditions: Liver Regeneration
• Intervention / Treatment: Drug: pentoxyfilline; Drug: Placebo

Detailed Description

Liver resection is for many patients with primary or secondary hepatic malignancies the only curative treatment option. Often, the complete clearance of the hepatic tumor disease can be only achieved by extended liver resections. Clinical studies have demonstrated that intra-operative blood loss is associated reduced outcome after major liver resection. An effective strategy to reduce blood loss is the occlusion of the portal triad (Pringle manoeuvre). On the other hand, inflow occlusion results in ischemia- and reperfusion (I/R) injury. Randomized trials have shown that ischemic preconditioning (10 min clamping, 10 min reperfusion) and intermittent clamping (15 min clamping, 5 min reperfusion) result in reduction of the I/R injury. Another potential strategy to reduce I/R injury is the pharmacological protection. One promising drug is pentoxyfilline (PTF) which has vasodilative and hemorheologic effects. Furthermore, PTF suppresses the TNF release. These effects may be also protective in major liver resection under inflow occlusion (Pringle manoeuvre)and increase the liver regeneration. Therefore, we designed a randomised prospective trial to investigate the effects of PTF treatment in liver resection under inflow occlusion. The specific aims of the research project are:The investigators hypothecate that pentoxyfilline increases significantly the liver regeneration and reduces significantly ischemia and reperfusion (I/R) injury in liver using aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as marker of I/R injury.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Zürich
    • Zurich, Zürich, Switzerland, 8091
      • University Hospital Zurich, Department of Visceral and Transplantation Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years
• Major liver resection (hemihepatectomies and extended hemihepatectomies) for benign and malignant lesions
• Macroscopic and microscopic normal liver parenchyma
• No underlying liver disease
• Normal preoperative liver tests (quick, bilirubin, AST, ALT)
• Signed informed consent

Exclusion Criteria:

• Age < 18 years
• Minor liver resections (less than hemihepatectomies) or wedge resections
• Macroscopic and microscopic appearance of liver fibrosis or cirrhosis
• Underlying liver disease such as viral hepatitis, cirrhosis, etc.
• Pathological preoperative liver tests (quick, bilirubin, AST, ALT)
• Intolerance to xanthine derivatives
• History of myocardial or cerebrovascular insult
• Total vascular exclusion during liver resection
• Intra-operative detection of unresectable tumor disease
• No signed informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo group	Drug: Placebo; This group will be treated with saline solution at the same time points. The infusion volume and infusion rate of saline solution correspond to that of the PTF group.
Active Comparator: pentoxyfilline group	Drug: pentoxyfilline; The total dose of 1 mg/kg/h will be used. At the preoperative day half of the daily dose will be given as a 4-hour short-term infusion within 24 hours before surgery. Afterwards, a continuous intravenous infusion of PTX 1 mg/kg of body weight per hour will be started intra-operatively and will be continued for a total of 72 hours after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
I. To determine the regeneration of the liver after liver resection with and without PTF treatment	pre- and up to day 8 after liver resection

Secondary Outcome Measures

Outcome Measure	Time Frame
Il-6, TNF, procalcitonin for regeneration.AST & ALT peak for ischemic reperfusion injury. If PTF treatment has protective effects in steatotic/fibrotic liver.	pre- and up to 8 days postoperatively

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Pierre Alain Clavien, MD, PhD, Departmente of Visceral and Transplantation Surgery

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: August 11, 2009
• First Submitted That Met QC Criteria: August 11, 2009
• First Posted (Estimate): August 12, 2009

Study Record Updates

• Last Update Posted (Estimate): February 10, 2015
• Last Update Submitted That Met QC Criteria: February 9, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: pentoxyfilline; liver regeneration; major liver resection; reduction of the I/R injury
• Other Study ID Numbers: StV 7-2006