Hypothermic Perfusion During Hemihepatectomy

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor:
Information provided by (Responsible Party):
Megan J. Reiniers, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01499979
First received: December 20, 2011
Last updated: February 17, 2014
Last verified: February 2014
  Purpose

Rationale

Currently, hepatic resection is often the only curative treatment for primary or secondary hepatic malignancies and is also frequently performed in patients with benign liver tumors to prevent malignant transformation and/or alleviate symptoms. Liver resections are nowadays associated with low mortality and acceptable morbidity. As result of that, an increasing number of patients is currently under consideration for resection of more complex or large tumors, thus requiring extensive resection procedures. Application of vascular exclusion (i.e., clamping of the portal vein and hepatic artery) during such procedures reduces blood loss, which is one of the most important factors affecting peri-operative outcomes. However, vascular exclusion leads to ischemia-reperfusion (I/R) injury as an inevitable side-effect, which adversely impacts postoperative liver function and regeneration. Additional cooling of the liver by means of hypothermic perfusion is expected to further reduce intraoperative blood loss, as well as to protect the liver from I/R injury. Therefore, the aim of this pilot study is to cool the future remnant liver (FRL) in situ during right hemihepatectomy under vascular exclusion. Consequently, an overall improvement in postoperative outcomes is expected due to a decrease in intraoperative blood loss, reduced parenchymal damage, and a better ability of the liver remnant to regenerate.

Objective

To reduce intraoperative blood loss and enhance tolerance of the FRL to I/R injury during right hemihepatectomy under vascular exclusion by means of in situ hypothermic perfusion with retrograde outflow (R-IHP) of the FRL.

Study design

The study is designed as a prospective randomized pilot study in 18 patients (9 interventions and 9 controls) to assess the effects of the proposed intervention. Additionally, 4 patients will be included separately for assessment of the intervention's feasibility prior to randomized inclusion.

Study population

Eligible patients for participation in this study are those planned to undergo right hemihepatectomy under vascular inflow occlusion because of a malignant or benign liver tumor, and who do not suffer from any hepatic co-morbidity that might influence postoperative outcomes (i.e., severe steatosis, cholestasis, cirrhosis, or hepatitis B/C infection).

Intervention

During right hemihepatectomy, the FRL of patients allocated to the intervention group will be perfused with a chilled perfusion solution (i.e., lactated Ringer's solution).


Condition Intervention
Hepatic Ischemia-reperfusion Injury
Procedure: In situ hypothermic perfusion

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: In Situ Hypothermic Perfusion During Right Hemihepatectomy

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • Postoperative hepatocellular damage [ Time Frame: 5 days postoperatively ] [ Designated as safety issue: No ]
    Hepatocellular damage expressed as an postoperative increase in transaminases (i.e., AST and ALT).


Secondary Outcome Measures:
  • Intraoperative blood loss [ Time Frame: 2-3 hours ] [ Designated as safety issue: No ]
    Blood loss during surgery

  • Postoperative complications [ Time Frame: 5 days postoperatively ] [ Designated as safety issue: No ]
    Incidence of surgery-related complications

  • Regeneration of liver function and volume [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    Regeneration of liver function (measured via hepatobiliary scintigraphy) and -volume (measured via CT volumetry).


Estimated Enrollment: 22
Study Start Date: February 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Vascular inflow occlusion
Patients that will receive intermittent vascular inflow occlusion, the standard method for vascular occlusion at our institution, during liver resection.
Experimental: Hypothermic perfusion
Patients will receive in situ hypothermic perfusion of the future remnant liver during liver resection.
Procedure: In situ hypothermic perfusion
In situ perfusion of the future remnant liver with chilled lactated Ringer's solution during liver resection.
Other Name: In situ hypothermic preservation

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients scheduled for right hemihepatectomy under vascular inflow occlusion for a malignant or benign hepatic tumor
  • Diagnostic exclusion of hepatic co-morbidity, that is:

    • Cirrhosis,
    • Severe steatosis (≥ 30%),
    • Cholestasis, and
    • Hepatitis B/C infection
  • Age ≥ 18 years
  • Signed informed consent obtained prior to any study-specific procedure
  • ASA classification I-III

Exclusion Criteria:

  • Patients diagnosed with any of the hepatic co-morbidities listed under point 2 of the inclusion criteria
  • Age < 18 years
  • BMI > 35 kg/m2
  • ASA classification IV/V
  • Patient is scheduled for a combined surgical procedure (e.g., bile duct resection, gastrointestinal procedures)
  • Patient underwent liver resection ≤ 1 year prior to scheduled surgery
  • Emergency operations
  • Pregnancy or breast feeding
  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: NCT01499979

Contacts
Contact: Megan J. Reiniers, MSc +31205666683 m.j.reiniers@amc.uva.nl
Contact: Prof. Thomas M. van Gulik, MD, PhD +31205665570 t.m.vangulik@amc.uva.nl

Locations
Netherlands
Academic Medical Center (AMC) Recruiting
Amsterdam, Noord-Holland, Netherlands, 1105 AZ
Contact: Megan J. Reiniers, MSc    +31205666683    m.j.reiniers@amc.uva.nl   
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Study Chair: Prof. Thomas M. van Gulik, MD, PhD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Principal Investigator: Megan J. Reiniers, MSc Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Principal Investigator: Rowan F. van Golen, MSc Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  More Information

Publications:
Responsible Party: Megan J. Reiniers, PhD student, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01499979     History of Changes
Other Study ID Numbers: 2011_214, NL37241.018.11
Study First Received: December 20, 2011
Last Updated: February 17, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Ischemia-reperfusion injury
In situ hypothermic perfusion
In situ hypothermic preservation

Additional relevant MeSH terms:
Hypothermia
Ischemia
Reperfusion Injury
Wounds and Injuries
Body Temperature Changes
Signs and Symptoms
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications

ClinicalTrials.gov processed this record on July 26, 2014