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

• Sponsor: University of Zurich (Other)
• Overall Status: Completed
• CT.gov ID: NCT00957619
• Collaborator: (none)
• Enrollment: 100
• Location: 1
• Arms: 2
• Duration (Months): 46.1
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Regeneration	Drug: pentoxyfilline; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Study of the Protective Effect of Mechanism of Pentoxyfilline After Major Liver Resection Under Inflow Occlusion (Pringle Manoeuvre)
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: pentoxyfilline group 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.
Placebo Comparator: placebo group 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.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Zurich, Department of Visceral and Transplantation Surgery	Zurich	Zürich	Switzerland	8091

Sponsors and Collaborators

• University of Zurich

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ksenija Slankamenac, MD PhD, University of Zurich
• ClinicalTrials.gov Identifier: NCT00957619
• Other Study ID Numbers: StV 7-2006
• First Posted: Aug 12, 2009
• Last Update Posted: Feb 10, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by Ksenija Slankamenac, MD PhD, University of Zurich: pentoxyfilline; liver regeneration; major liver resection; reduction of the I/R injury

Study Results

No Results Posted as of Feb 10, 2015