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

August 11, 2009
January 22, 2010
March 2006
January 2010   (final data collection date for primary outcome measure)
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 ]
I. To determine peak AST and ALT after major liver resection with and without PTF treatment. [ Time Frame: pre- and up to 8 days postoperatively ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00957619 on ClinicalTrials.gov Archive Site
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 ]
II. To determine blood TNF, IL-6, and procalcitonin III. To investigate if PTF treatment has protective effects in diseased liver (steatosis, fibrosis). IV. To investigate if PTF treatment is effective in short- and/or long-term inflow occlusion. [ Time Frame: pre- and up to 8 days postoperatively ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Study of the Protective Effect of Mechanism of Pentoxyfilline After Major Liver Resection Under Inflow Occlusion (Pringle Manoeuvre)
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.

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.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Liver Regeneration
  • 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.
  • 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
    pentoxyfilline group
    Intervention: Drug: pentoxyfilline
  • Placebo Comparator: placebo group
    placebo group
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
100
January 2010
January 2010   (final data collection date for primary outcome measure)

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
Both
18 Years to 90 Years
No
Contact information is only displayed when the study is recruiting subjects
Switzerland
 
NCT00957619
StV 7-2006
No
Clavien, Pierre Alain, Prof. Dr. med., PhD, FACS, FRACS, Department of Visceral and Transplantation Surgery
University of Zurich
Not Provided
Principal Investigator: Pierre Alain Clavien, MD, PhD Departmente of Visceral and Transplantation Surgery
University of Zurich
January 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP