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

This study has been completed.
Sponsor:
Information provided by:
University of Zurich
ClinicalTrials.gov Identifier:
NCT00957619
First received: August 11, 2009
Last updated: January 22, 2010
Last verified: January 2010
  Purpose

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 Intervention Phase
Liver Regeneration
Drug: pentoxyfilline
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Study of the Protective Effect of Mechanism of Pentoxyfilline After Major Liver Resection Under Inflow Occlusion (Pringle Manoeuvre)

Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • I. To determine the regeneration of the liver after liver resection with and without PTF treatment [ Time Frame: pre- and up to day 8 after liver resection ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Il-6, TNF, procalcitonin for regeneration.AST & ALT peak for ischemic reperfusion injury. If PTF treatment has protective effects in steatotic/fibrotic liver. [ Time Frame: pre- and up to 8 days postoperatively ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: March 2006
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00957619

Locations
Switzerland
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
  More Information

No publications provided

Responsible Party: Clavien, Pierre Alain, Prof. Dr. med., PhD, FACS, FRACS, Department of Visceral and Transplantation Surgery
ClinicalTrials.gov Identifier: NCT00957619     History of Changes
Other Study ID Numbers: StV 7-2006
Study First Received: August 11, 2009
Last Updated: January 22, 2010
Health Authority: Switzerland: Ethic committee of the Kanton Zürich

Keywords provided by University of Zurich:
pentoxyfilline
liver regeneration
major liver resection
reduction of the I/R injury

ClinicalTrials.gov processed this record on August 27, 2014