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

Liver Regeneration Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00957619
• Other study ID #: StV 7-2006
• Status: Completed
• Phase: Phase 4
• First received: August 11, 2009
• Last updated: February 9, 2015
• Start date: March 2006
• Est. completion date: January 2010

Study information

• Verified date: February 2015
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethic committee of the Kanton Zürich
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Regeneration

Intervention

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.
• 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.

Locations

Country	Name	City	State
Switzerland	University Hospital Zurich, Department of Visceral and Transplantation Surgery	Zurich	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes