<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01696630</url>
  </required_header>
  <id_info>
    <org_study_id>XENON</org_study_id>
    <secondary_id>2012-002155-41</secondary_id>
    <secondary_id>ET2012-19</secondary_id>
    <nct_id>NCT01696630</nct_id>
  </id_info>
  <brief_title>Xenon Combined With Intraoperative Thoracic Epidural Analgesia</brief_title>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Leon Berard</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Leon Berard</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a monocentric study in 2 steps: A safety part to assess the feasibility of using&#xD;
      Xenon in association with a thoracic epidural analgesia (TEA) with a sequential recruitment&#xD;
      of 3, 6 or 9 patients according to predefined safety rules. The second part will randomly&#xD;
      allocated patients (1:1) to receive TEA+Xenon or TEA+Desflurane. 28 patients will be enrolled&#xD;
      and followed over 45 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The first step is divided into 3 parts. 9 patients will be sequentially enrolled (3 patients&#xD;
      in each part). The patients will be followed during 45 days and the following rules will be&#xD;
      used to assess the safety:&#xD;
&#xD;
      First part: if no toxicity: initiation of the randomised part. If 1/3 toxicity: start of the&#xD;
      second part. If 2 or 3/3 toxicity: end of the study.&#xD;
&#xD;
      Second part: same rules and possible start of the third part. Third part: if no toxicity:&#xD;
      initiation of the randomised part. If 1 or more toxicity: end of the study.&#xD;
&#xD;
      The safety will be assessed after each part by an independent data safety monitoring board.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Variation of intraoperative Mean Arterial Pressure (MAP)</measure>
    <time_frame>Maintenance phase</time_frame>
    <description>Variation between the Mean Arterial Pressure (MAP) at induction and the mean of intraoperative MAP values in each patient and comparaison between arms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measure of hemodynamic parameters (Systolic Ejection Volume, Heart rate, DeltaPP)</measure>
    <time_frame>Throughout the maintenance of anesthesia, an expected average of 6 hours</time_frame>
    <description>monitoring device (automatic recorder)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delay from the surgery to the discharge date</measure>
    <time_frame>from the surgery to the hospital discharge date</time_frame>
    <description>Delay from the date of surgery to the date of hospital discharge (days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delay between the end of surgery and Post Anesthesia Care Unit's exit (min)</measure>
    <time_frame>from the end of surgery up to Post Anesthesia Care Unit's exit</time_frame>
    <description>Delay between the end of surgery and Post Anesthesia Care Unit's exit (min)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total dose requirement of Vasopressive and hypotensive agents</measure>
    <time_frame>Throughout the maintenance of anesthesia, an expected average of 6 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of each product infused</measure>
    <time_frame>Throughout the maintenance of anesthesia, an expected average of 6 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total dose of morphine</measure>
    <time_frame>Throughout the maintenance of anesthesia, an expected average of 6 hours</time_frame>
    <description>Total dose of morphine required to maintain BIS between 40 and 60 (in mg/kg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of awaking</measure>
    <time_frame>5 minutes after eyes opening</time_frame>
    <description>Modified Aldrete score and Recovery Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delay to oral feeding recovery</measure>
    <time_frame>From surgery to oral feeding reintroduction</time_frame>
    <description>Time from the date of surgery to the date of first subsequent oral food intake</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-operative Adverse Events</measure>
    <time_frame>45 days after surgery</time_frame>
    <description>Post-operative Adverse Events (according to the NCI-CTC version 4.03)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>post-operative pain</measure>
    <time_frame>At entrance and exit of post operative room and 24 hours after the end of anesthesia</time_frame>
    <description>Score to Visual Analog Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delay to intestinal transit recovery</measure>
    <time_frame>Time to postoperative stools</time_frame>
    <description>Time from the date of surgery to the date of first postoperative stools</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Desflurane</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Desflurane 6.5% (+/-0.5%) in association with a thoracic epidural analgesia in maintenance phase</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Xenon</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Xenon 60% (+/-5%) in association with a thoracic epidural analgesia in maintenance phase</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Xenon</intervention_name>
    <arm_group_label>Xenon</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Desflurane</intervention_name>
    <arm_group_label>Desflurane</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Older than 18 years old&#xD;
&#xD;
          -  Planned surgery for oncologic colic and/or rectal surgery&#xD;
&#xD;
          -  ASA score I or II&#xD;
&#xD;
          -  Indication of complementary thoracic epidural analgesia&#xD;
&#xD;
          -  Agree to use an effective form of contraception&#xD;
&#xD;
          -  Patients who can understand, read and write French language&#xD;
&#xD;
          -  Covered by a medical insurance&#xD;
&#xD;
          -  Patients who have dated/signed an inform consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unstable angina within the 30 last days&#xD;
&#xD;
          -  Myocardial infarction within 28 days prior to surgery&#xD;
&#xD;
          -  Uncontrolled arterial high blood pressure&#xD;
&#xD;
          -  Severe cardiac insufficiency&#xD;
&#xD;
          -  Severe chronic obstructive pneumopathy&#xD;
&#xD;
          -  Patient who requires FiO2 &gt; 40%&#xD;
&#xD;
          -  Patient already enrolled in a clinical study which may interfere with the present&#xD;
             study&#xD;
&#xD;
          -  Known hypersensitivity to one of the study drugs&#xD;
&#xD;
          -  History or familial history of malignant hyperthermia&#xD;
&#xD;
          -  Documented high intracranial pressure&#xD;
&#xD;
          -  Eclampsia or pre-eclampsia&#xD;
&#xD;
          -  Pregnant or breastfeeding woman&#xD;
&#xD;
          -  Liver injury (icterus) and/or unexplained fever and/or eosinophilia after halogen&#xD;
             exposure&#xD;
&#xD;
          -  Failure in epidural anesthesia installation&#xD;
&#xD;
          -  Patient refusal&#xD;
&#xD;
          -  Patient who can't be compliant to the present protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Centre Léon Bérard</name>
      <address>
        <city>LYON Cedex 08</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>11379681</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>16782975</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>18165567</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>14834873</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>17325504</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>17468494</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>7909641</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>12502972</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>10434815</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>20459661</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>18952398</PMID>
  </reference>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>September 21, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2012</study_first_posted>
  <last_update_submitted>August 3, 2016</last_update_submitted>
  <last_update_submitted_qc>August 3, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 4, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>anesthesia, epidural anagesia, colorectal surgery, xenon, hemodynamic change</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Desflurane</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01696630
org study id: XENON
secondary id: 2012-002155-41
secondary id: ET2012-19
nct id: NCT01696630
lead sponsor: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Single (Participant)
measure: Variation of intraoperative Mean Arterial Pressure (MAP)
time frame: Maintenance phase
description: Variation between the Mean Arterial Pressure (MAP) at induction and the mean of intraoperative MAP values in each patient and comparaison between arms.
measure: Measure of hemodynamic parameters (Systolic Ejection Volume, Heart rate, DeltaPP)
time frame: Throughout the maintenance of anesthesia, an expected average of 6 hours
description: monitoring device (automatic recorder)
measure: Delay from the surgery to the discharge date
time frame: from the surgery to the hospital discharge date
description: Delay from the date of surgery to the date of hospital discharge (days)
measure: Delay between the end of surgery and Post Anesthesia Care Unit's exit (min)
time frame: from the end of surgery up to Post Anesthesia Care Unit's exit
description: Delay between the end of surgery and Post Anesthesia Care Unit's exit (min)
measure: Total dose requirement of Vasopressive and hypotensive agents
time frame: Throughout the maintenance of anesthesia, an expected average of 6 hours
measure: Volume of each product infused
time frame: Throughout the maintenance of anesthesia, an expected average of 6 hours
measure: Total dose of morphine
time frame: Throughout the maintenance of anesthesia, an expected average of 6 hours
description: Total dose of morphine required to maintain BIS between 40 and 60 (in mg/kg)
measure: Quality of awaking
time frame: 5 minutes after eyes opening
description: Modified Aldrete score and Recovery Index
measure: Delay to oral feeding recovery
time frame: From surgery to oral feeding reintroduction
description: Time from the date of surgery to the date of first subsequent oral food intake
measure: Post-operative Adverse Events
time frame: 45 days after surgery
description: Post-operative Adverse Events (according to the NCI-CTC version 4.03)
measure: post-operative pain
time frame: At entrance and exit of post operative room and 24 hours after the end of anesthesia
description: Score to Visual Analog Scale
measure: Delay to intestinal transit recovery
time frame: Time to postoperative stools
description: Time from the date of surgery to the date of first postoperative stools
arm group label: Desflurane
arm group type: Active Comparator
description: Desflurane 6.5% (+/-0.5%) in association with a thoracic epidural analgesia in maintenance phase
arm group label: Xenon
arm group type: Experimental
description: Xenon 60% (+/-5%) in association with a thoracic epidural analgesia in maintenance phase
intervention type: Drug
intervention name: Xenon
arm group label: Xenon
intervention type: Drug
intervention name: Desflurane
arm group label: Desflurane
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: France
citation: 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.
PMID: 11379681
citation: 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.
PMID: 16782975
citation: 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.
PMID: 18165567
citation: 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.
PMID: 14834873
citation: 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.
PMID: 17325504
citation: 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.
PMID: 17468494
citation: 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.
PMID: 7909641
citation: 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.
PMID: 12502972
citation: 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.
PMID: 10434815
citation: 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.
PMID: 20459661
citation: 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.
PMID: 18952398
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Desflurane