Xenon-anesthesia on Patients Undergoing Major Liver-resection (XeLiv)

Xenon-anesthesia on Patients Undergoing Major Liver-resection: Randomized Controlled Trial

The aim of this study is to compare the postoperative outcome of patients undergoing major liver resection under xenon- compared to desflurane-anesthesia.

Study Overview

• Status: Withdrawn
• Conditions: Liver Function After Partial Liver Resection
• Intervention / Treatment: Drug: Xenon; Drug: Desflurane

Detailed Description

The aim of this study is to compare the postoperative liver function and additional outcome parameters of patients undergoing major liver resection under xenon- compared to desflurane-anesthesia. Xenon is known to maintain hemodynamic stability and consecutive tissue perfusion. Together with its potential for ischemic pre-conditioning, we hypothesize a protective effect of xenon on post-operative liver failure and ischemia/reperfusion injury.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • University Hospital RWTH Aachen University, Department of Anesthesiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 3 segments liver resection
• ≥ 18 years
• Both gender
• American Society of Anesthesiologists (ASA) classification I-III
• Written informed consent prior to study participation

Exclusion Criteria:

Subjects, fulfilling one or more of the following exclusion criteria will not be included in the study:

• Severe pulmonary or airway disease
• Severe liver disease, accompanied by a Child-Pugh class >A
• Allergy/hypersensitivity to study medications
• ASA ≥ IV
• Patients susceptible to malignant hyperthermia
• Women who are pregnant, breast-feeding or women of childbearing potential not using adequate contraceptive methods
• Patients with preeclampsia or eclampsia
• Patients legally unable to give written informed consent.
• Patients with risk of high oxygen demand
• Patient with seriously impaired cardiac function
• All contraindications for xenon anesthesia according to the summary of product characteristics LENOXe
• Patient participates in a parallel interventional clinical trial during this study or receives an investigational drug within 30 days prior to inclusion into this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xenon; Xenon concentration of 50-60 % will be used for maintenance of general anesthesia and will be adjusted to maintain Bispectral index (BIS) value between 40 and 60.	Drug: Xenon; inhalation to maintain anesthesia; Other Names: LenoXe
Active Comparator: Desflurane; Desflurane concentrations of 4-5%/0.8 minimum alveolar concentration (MAC) respectively will be used for maintenance of general anesthesia and will be adjusted to maintain BIS index value between 40 and 60.	Drug: Desflurane; inhalation to maintain anesthesia; Other Names: Suprane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-course of postoperative liver injury and function	The primary study outcome is the difference in postoperative liver injury and function between the two study arms, measured by the perioperative time-course of the liver transaminase alanine-aminotransferase (ALAT) preoperative and on postoperative days (POD) 1-3, 5 and 7.	Within the first 7 postoperative days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intra- and postoperative blood loss	Difference of intra- and postoperative blood loss between the two study arms until discharge from ICU or POD 7 (whichever occurs first)	Surgery and ICU stay (maximum POD 7)
Quantity of intra- and postoperative infusions	Difference in quantity of infused crystalloids abd colloids between the two study arms until discharge from ICU or POD 7 (whichever occurs first)	Surgery and ICU stay (maximum POD 7)
Quantity of intra- and postoperative blood products	Difference in quantity of transfused packed red blood cells (RBCs), fresh frozen plasma (FFP) and platelet concentrates between the two study arms until discharge from ICU or POD 7 (whichever occurs first)	Surgery and ICU stay (maximum POD 7)
Quantity of intra- and postoperative coagulation products	Difference in quantity of administered tranexamic acid, fibrinogen and prothrombin complex concentrates between the two study arms until discharge from ICU or POD 7 (whichever occurs first)	Surgery and ICU stay (maximum POD 7)
Necessity and duration of surgical pringle maneuver	Difference in necessity and duration of intraoperative pringle maneuver performed by the surgeon between study groups	Surgery
Necessity and duration of surgical total vascular occlusion	Difference in necessity and duration of intraoperative total vascular occlusion performed by the surgeon between study groups	Surgery
Surgery time	Difference in surgery time between study groups	Surgery
Fibrosis in the resected liver tissue	Difference in fibrosis in the resected liver tissue between the two study arms	Surgery
Number of hepatocytes in synthesis phase in the resected liver tissue	Difference in number of hepatocytes in synthesis phase in the resected liver tissue between the two study arms	Surgery
Number of macrophages in the resected liver tissue	Difference in number of macrophages in the resected liver tissue between the two study arms	Surgery
Expression of Interleukin 6 (IL-6) in the resected liver tissue	Difference in expression of Interleukin 6 (IL-6) in the resected liver tissue between the two study arms	Surgery
Expression of tumor necrosis factor (TNF) in the resected liver tissue	Difference in expression of tumor necrosis factor (TNF) in the resected liver tissue between the two study arms	Surgery
Expression of hepatocyte growth factor (HGF) in the resected liver tissue	Difference in expression of hepatocyte growth factor (HGF) in the resected liver tissue between the two study arms	Surgery
Expression of epidermal growth factor (EGF) in the resected liver tissue	Difference in expression of epidermal growth factor (EGF) in the resected liver tissue between the two study arms	Surgery
Expression of fibroblast growth factor (FGF) in the resected liver tissue	Difference in expression of fibroblast growth factor (FGF) in the resected liver tissue between the two study arms	Surgery
Expression of insulin-like growth factors I/II (IGF-I/II) in the resected liver tissue	Difference in expression of insulin-like growth factors I/II (IGF-I/II) in the resected liver tissue between the two study arms	Surgery
Weight of the resected liver tissue	Difference in weight of the resected liver tissue normalized to body weight (%BW) between the two study arms	Surgery
Computer tomography-assisted planimetry of the resected liver tissue	Difference in area of the resected liver tissue, assessed with computer tomography assisted planimetry, between the two study arms	Surgery
Time-course of hemoglobin (Hb)	Difference in laboratory data, measured by the time-course of hemoglobin (Hb), between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first)	Within the first 7 postoperative days
Time-course of platelet count	Difference in laboratory data, measured by the time-course of platelet count, between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first)	Within the first 7 postoperative days
Time-course of prothrombin time (PT)	Difference in laboratory data, measured by the time-course of prothrombin time (PT), between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first)	Within the first 7 postoperative days
Time-course of partial thromboplastin time (PTT)	Difference in laboratory data, measured by the time-course of partial thromboplastin time (PTT), between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first)	Within the first 7 postoperative days
Time-course of bilirubin	Difference in laboratory data, measured by the time-course of bilirubin, between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first)	Within the first 7 postoperative days
Time-course of aspartate aminotransferase (ASAT)	Difference in laboratory data, measured by the time-course of aspartate aminotransferase (ASAT), between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first)	Within the first 7 postoperative days
Time-course of creatinine	Difference in laboratory data, measured by the time-course of creatinine, between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first)	Within the first 7 postoperative days
Time-course of lactate	Difference in laboratory data, measured by the time-course of lactate, between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first)	Within the first 7 postoperative days
Time-course of albumin	Difference in laboratory data, measured by the time-course of albumin, between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first)	Within the first 7 postoperative days
Time-course of international normalized ratio (INR)	Difference in laboratory data, measured by the time-course of international normalized ratio (INR) levels, between the two study arms postoperatively until discharge from ICU or POD 7 (whichever occurs first)	Within the first 7 postoperative days
Postoperative peak of blood lactate	Difference in postoperative peak of blood lactate between the two study groups until discharge from ICU or POD 7 (whichever occurs first)	During ICU stay, maximum POD 7
Length of ICU stay	Difference in ICU length of stay between the two study arms	Until postoperative day 30
Length of hospital stay	Difference in hospital length of stay between the two study arms	Until postoperative day 30
Postoperative mortality	Difference in mortality between the two study arms until postoperative day 30	Until postoperative day 30
Adverse events	Difference in quality and quantity of adverse events between the two study arms	Until postoperative day 30
Difference in mortality, assessed by 30 days follow up via phone	Difference in mortality between the two study arms	Postoperative day 30
Difference in coagulation disorder, assessed by 30 days follow up via phone	Difference in coagulation disorder between the two study arms	Postoperative day 30
Difference in re-admission to hospital, assessed by 30 days follow up via phone	Difference in re-admission to hospital between the two study arms	Postoperative day 30
Difference in other adverse events, assessed by 30 days follow up via phone	Difference in other adverse events between the two study arms	Postoperative day 30

Collaborators and Investigators

• Sponsor: RWTH Aachen University
• Investigators: Principal Investigator: Ana Kowark, MD, RWTH Aachen University Hospital; Study Director: Mark Coburn, MD, PhD, RWTH Aachen University Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 11, 2018
• Primary Completion (Actual): September 27, 2019
• Study Completion (Actual): September 27, 2019

Study Registration Dates

• First Submitted: March 14, 2018
• First Submitted That Met QC Criteria: April 19, 2018
• First Posted (Actual): April 20, 2018

Study Record Updates

• Last Update Posted (Actual): October 29, 2019
• Last Update Submitted That Met QC Criteria: October 25, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: RCT; Desflurane; Xenon; Liver resection; post-operative liver failure; Randomized controlled trail; anesthetics, inhalation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Desflurane
• Other Study ID Numbers: 15-163

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No