XeLiv: Xenon-anesthesia on Patients Undergoing Major Liver-resection

• Sponsor: RWTH Aachen University (Other)
• Overall Status: Withdrawn
• CT.gov ID: NCT03504033
• Collaborator: (none)
• Enrollment: 0
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 17.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Liver Function After Partial Liver Resection	Drug: Xenon; Drug: Desflurane	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Single-center, controlled, double-blinded, randomized, two-arm parallel, interventional clinical trialSingle-center, controlled, double-blinded, randomized, two-arm parallel, interventional clinical trial
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: This trial will be performed double-blinded. After randomization neither the patients nor the investigator of the baseline assessment and the postoperative assessment will be aware of the treatment allocation. The intraoperative anesthesiologist will not be blinded, due to feasibility and safety reasons.
• Primary Purpose: Treatment
• Official Title: Xenon-anesthesia on Patients Undergoing Major Liver-resection: Randomized Controlled Trial
• Anticipated Study Start Date: Apr 11, 2018
• Actual Primary Completion Date: Sep 27, 2019
• Actual Study Completion Date: Sep 27, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Time-course of postoperative liver injury and function [Within the first 7 postoperative days]

   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.

Secondary Outcome Measures

1. Intra- and postoperative blood loss [Surgery and ICU stay (maximum POD 7)]

   Difference of intra- and postoperative blood loss between the two study arms until discharge from ICU or POD 7 (whichever occurs first)

2. Quantity of intra- and postoperative infusions [Surgery and ICU stay (maximum POD 7)]

   Difference in quantity of infused crystalloids abd colloids between the two study arms until discharge from ICU or POD 7 (whichever occurs first)

3. Quantity of intra- and postoperative blood products [Surgery and ICU stay (maximum POD 7)]

   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)

4. Quantity of intra- and postoperative coagulation products [Surgery and ICU stay (maximum POD 7)]

   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)

5. Necessity and duration of surgical pringle maneuver [Surgery]

   Difference in necessity and duration of intraoperative pringle maneuver performed by the surgeon between study groups

6. Necessity and duration of surgical total vascular occlusion [Surgery]

   Difference in necessity and duration of intraoperative total vascular occlusion performed by the surgeon between study groups

7. Surgery time [Surgery]

   Difference in surgery time between study groups

8. Fibrosis in the resected liver tissue [Surgery]

   Difference in fibrosis in the resected liver tissue between the two study arms

9. Number of hepatocytes in synthesis phase in the resected liver tissue [Surgery]

   Difference in number of hepatocytes in synthesis phase in the resected liver tissue between the two study arms

10. Number of macrophages in the resected liver tissue [Surgery]

    Difference in number of macrophages in the resected liver tissue between the two study arms

11. Expression of Interleukin 6 (IL-6) in the resected liver tissue [Surgery]

    Difference in expression of Interleukin 6 (IL-6) in the resected liver tissue between the two study arms

12. Expression of tumor necrosis factor (TNF) in the resected liver tissue [Surgery]

    Difference in expression of tumor necrosis factor (TNF) in the resected liver tissue between the two study arms

13. Expression of hepatocyte growth factor (HGF) in the resected liver tissue [Surgery]

    Difference in expression of hepatocyte growth factor (HGF) in the resected liver tissue between the two study arms

14. Expression of epidermal growth factor (EGF) in the resected liver tissue [Surgery]

    Difference in expression of epidermal growth factor (EGF) in the resected liver tissue between the two study arms

15. Expression of fibroblast growth factor (FGF) in the resected liver tissue [Surgery]

    Difference in expression of fibroblast growth factor (FGF) in the resected liver tissue between the two study arms

16. Expression of insulin-like growth factors I/II (IGF-I/II) in the resected liver tissue [Surgery]

    Difference in expression of insulin-like growth factors I/II (IGF-I/II) in the resected liver tissue between the two study arms

17. Weight of the resected liver tissue [Surgery]

    Difference in weight of the resected liver tissue normalized to body weight (%BW) between the two study arms

18. Computer tomography-assisted planimetry of the resected liver tissue [Surgery]

    Difference in area of the resected liver tissue, assessed with computer tomography assisted planimetry, between the two study arms

19. Time-course of hemoglobin (Hb) [Within the first 7 postoperative days]

    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)

20. Time-course of platelet count [Within the first 7 postoperative days]

    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)

21. Time-course of prothrombin time (PT) [Within the first 7 postoperative days]

    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)

22. Time-course of partial thromboplastin time (PTT) [Within the first 7 postoperative days]

    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)

23. Time-course of bilirubin [Within the first 7 postoperative days]

    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)

24. Time-course of aspartate aminotransferase (ASAT) [Within the first 7 postoperative days]

    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)

25. Time-course of creatinine [Within the first 7 postoperative days]

    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)

26. Time-course of lactate [Within the first 7 postoperative days]

    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)

27. Time-course of albumin [Within the first 7 postoperative days]

    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)

28. Time-course of international normalized ratio (INR) [Within the first 7 postoperative days]

    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)

29. Postoperative peak of blood lactate [During ICU stay, maximum POD 7]

    Difference in postoperative peak of blood lactate between the two study groups until discharge from ICU or POD 7 (whichever occurs first)

30. Length of ICU stay [Until postoperative day 30]

    Difference in ICU length of stay between the two study arms

31. Length of hospital stay [Until postoperative day 30]

    Difference in hospital length of stay between the two study arms

32. Postoperative mortality [Until postoperative day 30]

    Difference in mortality between the two study arms until postoperative day 30

33. Adverse events [Until postoperative day 30]

    Difference in quality and quantity of adverse events between the two study arms

34. Difference in mortality, assessed by 30 days follow up via phone [Postoperative day 30]

    Difference in mortality between the two study arms

35. Difference in coagulation disorder, assessed by 30 days follow up via phone [Postoperative day 30]

    Difference in coagulation disorder between the two study arms

36. Difference in re-admission to hospital, assessed by 30 days follow up via phone [Postoperative day 30]

    Difference in re-admission to hospital between the two study arms

37. Difference in other adverse events, assessed by 30 days follow up via phone [Postoperative day 30]

    Difference in other adverse events between the two study arms

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital RWTH Aachen University, Department of Anesthesiology	Aachen		Germany	52074

Sponsors and Collaborators

• RWTH Aachen University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: RWTH Aachen University
• ClinicalTrials.gov Identifier: NCT03504033
• Other Study ID Numbers: 15-163
• First Posted: Apr 20, 2018
• Last Update Posted: Oct 29, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by RWTH Aachen University: Xenon; Liver resection; post-operative liver failure; anesthetics, inhalation; Desflurane; Randomized controlled trail; RCT
• Additional relevant MeSH terms: Desflurane

Study Results

No Results Posted as of Oct 29, 2019