Effects of Propofol on Oxidative Stress and Liver Regeneration After Partial Hepatectomy

This study has been completed.
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by:
Rennes University Hospital
ClinicalTrials.gov Identifier:
NCT00219856
First received: September 13, 2005
Last updated: June 25, 2012
Last verified: June 2012

September 13, 2005
June 25, 2012
August 2004
March 2006   (final data collection date for primary outcome measure)
Plasma MDA levels [ Time Frame: 30 minutes after the end of hepatic clamping ] [ Designated as safety issue: No ]
Plasma MDA levels 30 minutes after the end of hepatic clamping
Complete list of historical versions of study NCT00219856 on ClinicalTrials.gov Archive Site
  • Kinetics of post surgical biological hepatic function recovery [ Time Frame: Days 1, 2, 5, 10 ] [ Designated as safety issue: No ]
    • Gamma gluatamyltransferase
    • ASAT
    • ALAT
    • Factor V
    • AlfagluthationeS-transferase
  • Kinetics of post surgical hepatic function recovery [ Time Frame: Day 2 ] [ Designated as safety issue: No ]
    Monoethylglycinexylidide (MEGX) test
  • Other biological markers of oxidative stress [ Time Frame: Days 1 and 2 ] [ Designated as safety issue: No ]
    • Glutathione
    • Myeloperoxidase
    • Nitric oxide
  • Hemodynamics during and after surgery [ Time Frame: Days 1 and 2 ] [ Designated as safety issue: No ]
    • Mean arterial pressure
    • Heart rate
    • Diuresis
  • Surgery related complications [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    • Liver insufficiency
    • Hepato renal syndrome
    • Local infections
  • Kinetics of post surgical hepatic function recovery:
  • - Gamma glutamyltransferase, ASAT, ALAT, factor V, alpha gluthatione S-transferase
  • - Monoethylglycinexylidide (MEGX) test
  • Other biological markers of oxidative stress:
  • - Glutathione, myeloperoxidase, nitric oxide
  • Hemodynamics during and after surgery:
  • - Mean arterial pressure, heart rate, diuresis
  • Surgery related complications:
  • - Liver insufficiency
  • - Hepato renal syndrome
  • - Infections
Not Provided
Not Provided
 
Effects of Propofol on Oxidative Stress and Liver Regeneration After Partial Hepatectomy
Prospective, Randomized, Simple Blind Study Comparing the Effects of an Anaesthesia With Propofol to an Anaesthesia With Desflurane on Oxydative Stress and Liver Function Recovery After Hepatectomy

Propofol is an anaesthetic agent that showed in vitro and in vivo anti oxidant properties. No data are available concerning the potential benefit of a total anaesthesia with propofol in partial hepatic surgery. Patients who undergo partial hepatic resection have frequent liver insufficiency that could be related in part to the oxidative stress induced by clamping the hepatic vessels during the surgical intervention. Our hypothesis is that propofol, by increasing liver resistance to this ischemia-reperfusion phenomenon, could improve the remaining liver function recovery, and therefore could reduce post surgical morbidity.

The aim of the study is to evaluate the anti oxidant effects of propofol compared to another widely used anaesthetic agent, inhaled desflurane, during and after partial hepatic resection with hepatic vessels clamping. The primary endpoint will be the level of malondialdehyde (a plasmatic marker of oxidative stress), 30 minutes after the end of hepatic clamping.

Propofol is an anaesthetic agent that showed in vitro and in vivo anti oxidant properties. No data are available concerning the potential benefit of a total anaesthesia with propofol in partial hepatic surgery. Patients who undergo partial hepatic resection have frequent liver insufficiency that could be related in part to the oxidative stress induced by clamping the hepatic hilum during the surgical intervention. Our hypothesis is that propofol, by increasing liver resistance to ischemic-reperfusion injury, could improve the remaining liver function recovery, and therefore could reduce post surgical morbidity.

The aim of the study is to evaluate the anti oxidant effects of propofol compared to another widely used anaesthetic agent, inhaled desflurane, during and after partial hepatic resection with hepatic hilum clamping.

The primary endpoint will be the level of malondialdehyde (a plasmatic marker of oxidative stress), 30 minutes after the end of hepatic clamping.

The evolution over time of other markers of oxidative stress will be studied (glutathione, myeloperoxidase, nitric oxide), as well as functional and biological markers of liver regeneration.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Hepatectomy
  • Drug: Propofol
    • Induction : intravenous propofol aiming a concentration of 4 to 8 µg/ml
    • Maintenance : intravenous propofol aiming a concentration of 3 to 6 µg/ml
  • Drug: Penthotal
    Intravenous penthotal at the dose of 3 to 5 mg/kg
  • Drug: Desflurane
    Inhaled desflurane aiming an alveolar concentration of 4 to 6 per cent.
  • Experimental: 1
    Anesthesic induction and maintenance with intravenous propofol.
    Intervention: Drug: Propofol
  • Active Comparator: 2
    Anesthesic induction with intravenous penthotal and maintenance with inhaled desflurane.
    Interventions:
    • Drug: Penthotal
    • Drug: Desflurane
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
34
March 2006
March 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients over 18
  • Need for partial hepatic resection requiring heptic clamping
  • Resection of 4 liver segments or less
  • In case of cirrhosis, child A
  • Written informed consent

Non-inclusion Criteria:

  • Hemochromatosis
  • chemotherapy in the previous week before inclusion
  • Thrombosis of the portal vein or the hepatic artery
  • Absence of contraception among fertil woman
  • Concomitant treatment that could have potential interaction with propofol
  • Concomitant treatment known to have antioxidant properties
  • Inclusion in another study protocol using a medication incompatible with the present study
  • Patient in which the follow up seems impossible
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00219856
AFSSAPS 040366, PHRC/03-02, CIC0203/026
No
Direction of Clinical Research, Rennes University Hospital
Rennes University Hospital
Ministry of Health, France
Principal Investigator: David Aguillon, MD Rennes University Hospital
Study Director: Yannick Malledant, MD Rennes University Hospital
Study Chair: Bruno Laviolle, MD Rennes University Hospital
Rennes University Hospital
June 2012

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