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

NCT ID: NCT00957619

Last Updated: 2015-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2010-01-31

Brief Summary

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.

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.

Conditions

Liver Regeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

pentoxyfilline group

pentoxyfilline group

Group Type: ACTIVE_COMPARATOR

pentoxyfilline

Intervention Type: DRUG

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.

placebo group

placebo group

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Ksenija Slankamenac

MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pierre Alain Clavien, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Departmente of Visceral and Transplantation Surgery

Locations

University Hospital Zurich, Department of Visceral and Transplantation Surgery

Zurich, Canton of Zurich, Switzerland

Countries

Switzerland

Other Identifiers

StV 7-2006

Identifier Type: -

Identifier Source: org_study_id