Xenon Combined With Intraoperative Thoracic Epidural Analgesia

Phase II Study, Randomized, Monocentric, Single-blind, Comparing the Efficacy of Xenon and Desflurane, in Association With a Thoracic Epidural Analgesia in the Maintenance Phase of a Colorectal Oncologic Surgery

This is a monocentric study in 2 steps: A safety part to assess the feasibility of using Xenon in association with a thoracic epidural analgesia (TEA) with a sequential recruitment of 3, 6 or 9 patients according to predefined safety rules. The second part will randomly allocated patients (1:1) to receive TEA+Xenon or TEA+Desflurane. 28 patients will be enrolled and followed over 45 days.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Xenon; Drug: Desflurane

Detailed Description

The first step is divided into 3 parts. 9 patients will be sequentially enrolled (3 patients in each part). The patients will be followed during 45 days and the following rules will be used to assess the safety:

First part: if no toxicity: initiation of the randomised part. If 1/3 toxicity: start of the second part. If 2 or 3/3 toxicity: end of the study.

Second part: same rules and possible start of the third part. Third part: if no toxicity: initiation of the randomised part. If 1 or more toxicity: end of the study.

The safety will be assessed after each part by an independent data safety monitoring board.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • LYON Cedex 08, France, 69373
    • Centre Léon Bérard

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:

• Older than 18 years old
• Planned surgery for oncologic colic and/or rectal surgery
• ASA score I or II
• Indication of complementary thoracic epidural analgesia
• Agree to use an effective form of contraception
• Patients who can understand, read and write French language
• Covered by a medical insurance
• Patients who have dated/signed an inform consent

Exclusion Criteria:

• Unstable angina within the 30 last days
• Myocardial infarction within 28 days prior to surgery
• Uncontrolled arterial high blood pressure
• Severe cardiac insufficiency
• Severe chronic obstructive pneumopathy
• Patient who requires FiO2 > 40%
• Patient already enrolled in a clinical study which may interfere with the present study
• Known hypersensitivity to one of the study drugs
• History or familial history of malignant hyperthermia
• Documented high intracranial pressure
• Eclampsia or pre-eclampsia
• Pregnant or breastfeeding woman
• Liver injury (icterus) and/or unexplained fever and/or eosinophilia after halogen exposure
• Failure in epidural anesthesia installation
• Patient refusal
• Patient who can't be compliant to the present protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Desflurane; Desflurane 6.5% (+/-0.5%) in association with a thoracic epidural analgesia in maintenance phase	Drug: Desflurane
EXPERIMENTAL: Xenon; Xenon 60% (+/-5%) in association with a thoracic epidural analgesia in maintenance phase	Drug: Xenon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variation of intraoperative Mean Arterial Pressure (MAP)	Variation between the Mean Arterial Pressure (MAP) at induction and the mean of intraoperative MAP values in each patient and comparaison between arms.	Maintenance phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of hemodynamic parameters (Systolic Ejection Volume, Heart rate, DeltaPP)	monitoring device (automatic recorder)	Throughout the maintenance of anesthesia, an expected average of 6 hours
Delay from the surgery to the discharge date	Delay from the date of surgery to the date of hospital discharge (days)	from the surgery to the hospital discharge date
Delay between the end of surgery and Post Anesthesia Care Unit's exit (min)	Delay between the end of surgery and Post Anesthesia Care Unit's exit (min)	from the end of surgery up to Post Anesthesia Care Unit's exit
Total dose requirement of Vasopressive and hypotensive agents		Throughout the maintenance of anesthesia, an expected average of 6 hours
Volume of each product infused		Throughout the maintenance of anesthesia, an expected average of 6 hours
Total dose of morphine	Total dose of morphine required to maintain BIS between 40 and 60 (in mg/kg)	Throughout the maintenance of anesthesia, an expected average of 6 hours
Quality of awaking	Modified Aldrete score and Recovery Index	5 minutes after eyes opening
Delay to oral feeding recovery	Time from the date of surgery to the date of first subsequent oral food intake	From surgery to oral feeding reintroduction
Post-operative Adverse Events	Post-operative Adverse Events (according to the NCI-CTC version 4.03)	45 days after surgery
post-operative pain	Score to Visual Analog Scale	At entrance and exit of post operative room and 24 hours after the end of anesthesia
Delay to intestinal transit recovery	Time from the date of surgery to the date of first postoperative stools	Time to postoperative stools

Collaborators and Investigators

• Sponsor: Centre Leon Berard

Publications and helpful links

General Publications

• Nakata Y, Goto T, Ishiguro Y, Terui K, Kawakami H, Santo M, Niimi Y, Morita S. Minimum alveolar concentration (MAC) of xenon with sevoflurane in humans. Anesthesiology. 2001 Apr;94(4):611-4. doi: 10.1097/00000542-200104000-00014.
• Rasmussen LS, Schmehl W, Jakobsson J. Comparison of xenon with propofol for supplementary general anaesthesia for knee replacement: a randomized study. Br J Anaesth. 2006 Aug;97(2):154-9. doi: 10.1093/bja/ael141. Epub 2006 Jun 17.
• Salmi E, Laitio RM, Aalto S, Maksimow AT, Langsjo JW, Kaisti KK, Aantaa R, Oikonen V, Metsahonkala L, Nagren K, Korpi ER, Scheinin H. Xenon does not affect gamma-aminobutyric acid type A receptor binding in humans. Anesth Analg. 2008 Jan;106(1):129-34, table of contents. doi: 10.1213/01.ane.0000287658.14763.13.
• CULLEN SC, GROSS EG. The anesthetic properties of xenon in animals and human beings, with additional observations on krypton. Science. 1951 May 18;113(2942):580-2. doi: 10.1126/science.113.2942.580. No abstract available.
• Wappler F, Rossaint R, Baumert J, Scholz J, Tonner PH, van Aken H, Berendes E, Klein J, Gommers D, Hammerle A, Franke A, Hofmann T, Schulte Esch J; Xenon Multicenter Study Research Group. Multicenter randomized comparison of xenon and isoflurane on left ventricular function in patients undergoing elective surgery. Anesthesiology. 2007 Mar;106(3):463-71. doi: 10.1097/00000542-200703000-00010.
• Baumert JH, Hein M, Hecker KE, Satlow S, Schnoor J, Rossaint R. Autonomic cardiac control with xenon anaesthesia in patients at cardiovascular risk. Br J Anaesth. 2007 Jun;98(6):722-7. doi: 10.1093/bja/aem083. Epub 2007 Apr 27.
• Luttropp HH, Thomasson R, Dahm S, Persson J, Werner O. Clinical experience with minimal flow xenon anesthesia. Acta Anaesthesiol Scand. 1994 Feb;38(2):121-5. doi: 10.1111/j.1399-6576.1994.tb03852.x.
• Rossaint R, Reyle-Hahn M, Schulte Am Esch J, Scholz J, Scherpereel P, Vallet B, Giunta F, Del Turco M, Erdmann W, Tenbrinck R, Hammerle AF, Nagele P; Xenon Study Group. Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery. Anesthesiology. 2003 Jan;98(1):6-13. doi: 10.1097/00000542-200301000-00005.
• Dupont J, Tavernier B, Ghosez Y, Durinck L, Thevenot A, Moktadir-Chalons N, Ruyffelaere-Moises L, Declerck N, Scherpereel P. Recovery after anaesthesia for pulmonary surgery: desflurane, sevoflurane and isoflurane. Br J Anaesth. 1999 Mar;82(3):355-9. doi: 10.1093/bja/82.3.355.
• Stuttmann R, Jakubetz J, Schultz K, Schafer C, Langer S, Ullmann U, Hilbert P. Recovery index, attentiveness and state of memory after xenon or isoflurane anaesthesia: a randomized controlled trial. BMC Anesthesiol. 2010 May 7;10:5. doi: 10.1186/1471-2253-10-5.
• Diemunsch P; Societe francaise d'anesthesie et de reanimation. [Conference of experts--short text. Management of postoperative nausea and vomiting. French Society of Anesthesia and Resuscitation]. Ann Fr Anesth Reanim. 2008 Oct;27(10):866-78. doi: 10.1016/j.annfar.2008.09.004. Epub 2008 Oct 25. No abstract available. French.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (ACTUAL): July 1, 2014
• Study Completion (ACTUAL): July 1, 2014

Study Registration Dates

• First Submitted: September 21, 2012
• First Submitted That Met QC Criteria: September 26, 2012
• First Posted (ESTIMATE): October 1, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): August 4, 2016
• Last Update Submitted That Met QC Criteria: August 3, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: anesthesia, epidural anagesia, colorectal surgery, xenon, hemodynamic change
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Desflurane
• Other Study ID Numbers: XENON; 2012-002155-41 (EUDRACT_NUMBER); ET2012-19 (OTHER: Sponsor's number)