<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/NCT01718756</url>
  </required_header>
  <id_info>
    <org_study_id>R/55</org_study_id>
    <nct_id>NCT01718756</nct_id>
  </id_info>
  <brief_title>Continuous Lornoxicam Infusion for Orthopaedic Surgery</brief_title>
  <official_title>Efficacy of Continuous Intravenous Infusion vs. Scheduled Dosing of Lornoxicam on Patient Controlled Morphine Consumption After Orthopaedic Surgery: A Comparative Placebo Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mansoura University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mansoura University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Perioperative continuous infusion of lornoxicam would be an effective and safe regimen to&#xD;
      reduce the patient controlled morphine consumption after orthopaedic surgery.&#xD;
&#xD;
      After ethical approval, 96 patients scheduled for elective orthopaedic fracture surgery under&#xD;
      general anaesthesia were randomly allocated to receive placebo, 12-hourly iv lornoxicam 16 mg&#xD;
      or lornoxicam 16 mg followed with continuous infusion of 1.3 mg/hr., for 48 hours after&#xD;
      surgery (n=32 per group). Anaesthesia was induced with propofol, sufentanil and rocuronium,&#xD;
      and was maintained with 0.5-1 minimum alveolar concentration sevoflurane, sufentanil and&#xD;
      rocuronium. Postoperative patient controlled morphine analgesia was used. Changes in heart&#xD;
      rate, mean blood pressure and sevoflurane minimum alveolar concentration, visual analogue&#xD;
      pain scores, and cumulative patient controlled morphine consumptions and blood loss for 48&#xD;
      hours, platelet functions, bone non-union and the presence of adverse effects were recorded.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An independent investigator who was not involved in the study instructed the patients&#xD;
      preoperatively about the use of visual analogue scale to assess the severity of postoperative&#xD;
      pain (0 mm for no pain and100 mm for worst imaginable pain) and about the use of PCA for&#xD;
      their postoperative pain management.&#xD;
&#xD;
      Anaesthetic management was standardized. Oral lorazepam 2 mg was given the night before&#xD;
      surgery. Subjects were allocated randomly into three groups (n = 32 for each) by drawing&#xD;
      sequentially numbered sealed opaque envelopes containing a software-generated randomization&#xD;
      code (Random Allocation Software, version 1.0.0, Isfahan University of Medical Sciences,&#xD;
      Isfahan, Iran)into the placebo, scheduled, and continuous infusion groups. The syringes&#xD;
      containing placebo and lornoxicam solutions were masked by identical opaque identical cover&#xD;
      sheets. The test solution was prepared by one anaesthesiologist before induction of&#xD;
      anaesthesia. Another anaesthesiologist, who was blinded to the study solution, gave the&#xD;
      anaesthetic and was instructed to avoid using local anaesthetics, and a third&#xD;
      anaesthesiologist collected perioperative data. All staff in the operating room were unaware&#xD;
      of patient allocation group.&#xD;
&#xD;
      Patient monitoring included electrocardiography, non-invasive blood pressure, pulse oximetry,&#xD;
      end-tidal sevoflurane and carbon dioxide (ETCO2) concentrations, response entropy (RE) and&#xD;
      state entropy (SE.&#xD;
&#xD;
      After preoxygenation for 3 min, anesthesia was induced with fentanyl 1 - 3 µg/kg, propofol&#xD;
      1.5-2.5 mg/kg (to achieve an SE &lt;50 and a difference&lt;10 between RE and SE; RE-SE) and&#xD;
      rocuronium 0.6 mg/kg. Tracheal intubation or slipping of laryngeal mask appropriate for body&#xD;
      weight were used according to the discretion of the attending anaesthetist. Anaesthesia was&#xD;
      maintained with a 0.6-1 minimum alveolar concentration of sevoflurane (MAC-Sevo) with air in&#xD;
      40% oxygen and fentanyl 1 µg/kg boluses to maintain SE &lt;50 and RE-SE &lt;10 and heart rate and&#xD;
      mean arterial blood pressure within 20% of their baseline values. Rocuronium 0.1 mg/kg was&#xD;
      given to maintain suppression of the second twitch using a train-of-four stimulation. The&#xD;
      patients' lungs were ventilated to maintain an ETCO2 of 30-35 mmHg. Sevoflurane were&#xD;
      discontinued at the start of skin closure, residual neuromuscular block was antagonized and&#xD;
      the trachea extubated.&#xD;
&#xD;
      Postoperative analgesia was achieved according to the hospital protocol with patient&#xD;
      controlled morphine analgesia (1 mg/ml), 1 mg, with a lockout interval of 8 minutes and a&#xD;
      maximum 24-hourly limit of 180 mg. respiratory depression defined as the decrease in&#xD;
      respiratory rate below 8/min was treated with i.v naloxone 0.2 mg. Nausea and vomiting were&#xD;
      treated with i.v granisetron 1 mg and pruritus was treated with i.m promethazine 25 mg.&#xD;
&#xD;
      Heart rate and mean arterial blood pressure were recorded before (baseline) and 10 min after&#xD;
      the start of infusion; every 30 min during surgery; every 15 min during the stay in post&#xD;
      anaesthesia care unit (PACU), and 8 hourly for the following 48 hours. MAC-Sevo was recorded&#xD;
      every 15 min after intubation until the end of surgery. Intraoperative fentanyl consumption&#xD;
      was recorded.&#xD;
&#xD;
      The VAS pain scores, the presence and intensity of postoperative sedation (four-point verbal&#xD;
      rating scores (VRS): awake, drowsy, rousable or deep sleep), nausea and vomiting (0: no&#xD;
      nausea; 1: nausea no vomiting; 2: nausea and vomiting), were reported every 15 min for the&#xD;
      first postoperative hour and two-hourly thereafter for the first 48 postoperative hours. The&#xD;
      cumulative morphine consumption during the first 24 and 48 postoperative hours were recorded.&#xD;
&#xD;
      Platelet function assay was performed before and every 24 hrs. for the first three days after&#xD;
      surgery. Cumulative intraoperative and postoperative blood loss and the number of transfused&#xD;
      blood units were recorded. The presence of fracture non-union was reported.&#xD;
&#xD;
      All patients were observed by an independent investigator during the study period for the&#xD;
      presence of nausea, vomiting, gastritis, reflux esophagitis, headache, bleeding,&#xD;
      bronchospasm, sweating, allergy, thrombocytopenia, bleeding, ecchymosis, or increases in&#xD;
      liver transaminases.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    No enough fund or cases&#xD;
  </why_stopped>
  <start_date type="Actual">June 2013</start_date>
  <completion_date type="Anticipated">February 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>Phase 1/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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>postoperative patient controlled morphine consumption</measure>
    <time_frame>24 hours and 48 hours after surgery</time_frame>
    <description>The cumulative morphine consumption during the first 24 and 48 postoperative hours were recorded.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of analgesia</measure>
    <time_frame>every two hours for 24 hours after surgery</time_frame>
    <description>the use of visual analogue scale to assess the severity of postoperative pain (0 mm for no pain and100 mm for worst imaginable pain)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>platelet functions</measure>
    <time_frame>daily after surgery for three days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone non-union</measure>
    <time_frame>for 3 months after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>postoperative sedation</measure>
    <time_frame>every two hours for 24 hours after surgery</time_frame>
    <description>four-point verbal rating scores (VRS): awake, drowsy, rousable or deep sleep),</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nausea and vomiting</measure>
    <time_frame>every two hours for 24 hours after surgery</time_frame>
    <description>nausea and vomiting (0: no nausea; 1: nausea no vomiting; 2: nausea and vomiting),</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perioperative blood loss</measure>
    <time_frame>Cumulative intraoperative and 24 hours after surgery</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Lornoxicam adverse effects</measure>
    <time_frame>48 hours after surgery</time_frame>
    <description>the presence of nausea, vomiting, gastritis, reflux esophagitis, headache, bleeding, bronchospasm, sweating, allergy, thrombocytopenia, bleeding, ecchymosis, or increases in liver transaminases.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">96</enrollment>
  <condition>Closed Non Comminuted Long Bone Fractures</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo group received 12 hourly boluses of 0.9% saline, followed by a constant infusion for 48 hrs after surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Scheduled</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>They received a 12 hourly boluses of lornoxicam followed by a constant infusion of 0.9% saline, for 48 hrs after surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continuous infusion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>They received boluses of lornoxicam 0.8 mg/mL before induction of anaesthesia followed by a 12 hourly boluses of 0.9% saline and a constant infusion at 10 mL/h of lornoxicam 0.13 mg/mL, for 48 hrs. after surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The placebo group received 12 hourly 20-mL i.v. boluses of 0.9% saline starting 20 min before induction of anaesthesia, followed by a constant infusion at 10 mL/h, for 48 hrs after surgery.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Continuous infusion</intervention_name>
    <description>The &quot;continuous infusion&quot; group received 20-mL i.v. boluses of lornoxicam 0.8 mg/mL starting 20 min before induction of anaesthesia followed by a 12 hourly 20-mL i.v. boluses of 0.9% saline and a constant infusion at 10 mL/h of lornoxicam 0.13 mg/mL, for 48 hrs. after surgery</description>
    <arm_group_label>Continuous infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Scheduled</intervention_name>
    <description>The &quot;scheduled&quot; group received an 12 hourly 20-mL i.v. boluses of lornoxicam 0.8 mg/mL starting 20 min before induction of anaesthesia followed by a constant infusion at 10 mL/h of 0.9% saline, for 48 hrs after surgery (supplied by Xefo, JPI, Saudi Arabia), starting 20 min before induction of anaesthesia.</description>
    <arm_group_label>Scheduled</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  American Society of Anesthesiologists physical class I to III&#xD;
&#xD;
          -  Age from 18 to 55 years&#xD;
&#xD;
          -  Closed non comminuted long bone fractures&#xD;
&#xD;
          -  Elective orthopaedic fracture surgery&#xD;
&#xD;
          -  General anaesthesia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hypersensitivity to lornoxicam&#xD;
&#xD;
          -  Gastrointestinal ulceration or bleeding&#xD;
&#xD;
          -  Cardiac diseases&#xD;
&#xD;
          -  Pulmonary diseases&#xD;
&#xD;
          -  Hepatic diseases&#xD;
&#xD;
          -  Renal diseases&#xD;
&#xD;
          -  Clotting diseases&#xD;
&#xD;
          -  Bleeding diseases&#xD;
&#xD;
          -  Bronchial asthma&#xD;
&#xD;
          -  Diabetes mellitus&#xD;
&#xD;
          -  Peripheral arterial occlusive disease&#xD;
&#xD;
          -  Morbid obesity&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Alcohol or drug abuse&#xD;
&#xD;
          -  Receiving other NSAIDs a day before surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mohamed R El Tahan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>College of Medicine, Mansoura University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Anesthesiology Dept., College of Medicine, Mansoura University</name>
      <address>
        <city>Mansoura</city>
        <state>DK</state>
        <zip>050</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>October 28, 2012</study_first_submitted>
  <study_first_submitted_qc>October 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>September 2, 2020</last_update_submitted>
  <last_update_submitted_qc>September 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mansoura University</investigator_affiliation>
    <investigator_full_name>Mohamed R El Tahan</investigator_full_name>
    <investigator_title>Associate Professor of Anesthesiology &amp; SICU</investigator_title>
  </responsible_party>
  <keyword>Orthopaedic</keyword>
  <keyword>General anaesthesia</keyword>
  <keyword>lornoxicam</keyword>
  <keyword>patient controlled analgesia</keyword>
  <keyword>morphine consumption</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fractures, Bone</mesh_term>
  </condition_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/NCT01718756
org study id: R/55
nct id: NCT01718756
lead sponsor: 
has dmc: Yes
Perioperative continuous infusion of lornoxicam would be an effective and safe regimen to
      reduce the patient controlled morphine consumption after orthopaedic surgery.

      After ethical approval, 96 patients scheduled for elective orthopaedic fracture surgery under
      general anaesthesia were randomly allocated to receive placebo, 12-hourly iv lornoxicam 16 mg
      or lornoxicam 16 mg followed with continuous infusion of 1.3 mg/hr., for 48 hours after
      surgery (n=32 per group). Anaesthesia was induced with propofol, sufentanil and rocuronium,
      and was maintained with 0.5-1 minimum alveolar concentration sevoflurane, sufentanil and
      rocuronium. Postoperative patient controlled morphine analgesia was used. Changes in heart
      rate, mean blood pressure and sevoflurane minimum alveolar concentration, visual analogue
      pain scores, and cumulative patient controlled morphine consumptions and blood loss for 48
      hours, platelet functions, bone non-union and the presence of adverse effects were recorded.
An independent investigator who was not involved in the study instructed the patients
      preoperatively about the use of visual analogue scale to assess the severity of postoperative
      pain (0 mm for no pain and100 mm for worst imaginable pain) and about the use of PCA for
      their postoperative pain management.

      Anaesthetic management was standardized. Oral lorazepam 2 mg was given the night before
      surgery. Subjects were allocated randomly into three groups (n = 32 for each) by drawing
      sequentially numbered sealed opaque envelopes containing a software-generated randomization
      code (Random Allocation Software, version 1.0.0, Isfahan University of Medical Sciences,
      Isfahan, Iran)into the placebo, scheduled, and continuous infusion groups. The syringes
      containing placebo and lornoxicam solutions were masked by identical opaque identical cover
      sheets. The test solution was prepared by one anaesthesiologist before induction of
      anaesthesia. Another anaesthesiologist, who was blinded to the study solution, gave the
      anaesthetic and was instructed to avoid using local anaesthetics, and a third
      anaesthesiologist collected perioperative data. All staff in the operating room were unaware
      of patient allocation group.

      Patient monitoring included electrocardiography, non-invasive blood pressure, pulse oximetry,
      end-tidal sevoflurane and carbon dioxide (ETCO2) concentrations, response entropy (RE) and
      state entropy (SE.

      After preoxygenation for 3 min, anesthesia was induced with fentanyl 1 - 3 µg/kg, propofol
      1.5-2.5 mg/kg (to achieve an SE <50 and a difference<10 between RE and SE; RE-SE) and
      rocuronium 0.6 mg/kg. Tracheal intubation or slipping of laryngeal mask appropriate for body
      weight were used according to the discretion of the attending anaesthetist. Anaesthesia was
      maintained with a 0.6-1 minimum alveolar concentration of sevoflurane (MAC-Sevo) with air in
      40% oxygen and fentanyl 1 µg/kg boluses to maintain SE <50 and RE-SE <10 and heart rate and
      mean arterial blood pressure within 20% of their baseline values. Rocuronium 0.1 mg/kg was
      given to maintain suppression of the second twitch using a train-of-four stimulation. The
      patients' lungs were ventilated to maintain an ETCO2 of 30-35 mmHg. Sevoflurane were
      discontinued at the start of skin closure, residual neuromuscular block was antagonized and
      the trachea extubated.

      Postoperative analgesia was achieved according to the hospital protocol with patient
      controlled morphine analgesia (1 mg/ml), 1 mg, with a lockout interval of 8 minutes and a
      maximum 24-hourly limit of 180 mg. respiratory depression defined as the decrease in
      respiratory rate below 8/min was treated with i.v naloxone 0.2 mg. Nausea and vomiting were
      treated with i.v granisetron 1 mg and pruritus was treated with i.m promethazine 25 mg.

      Heart rate and mean arterial blood pressure were recorded before (baseline) and 10 min after
      the start of infusion; every 30 min during surgery; every 15 min during the stay in post
      anaesthesia care unit (PACU), and 8 hourly for the following 48 hours. MAC-Sevo was recorded
      every 15 min after intubation until the end of surgery. Intraoperative fentanyl consumption
      was recorded.

      The VAS pain scores, the presence and intensity of postoperative sedation (four-point verbal
      rating scores (VRS): awake, drowsy, rousable or deep sleep), nausea and vomiting (0: no
      nausea; 1: nausea no vomiting; 2: nausea and vomiting), were reported every 15 min for the
      first postoperative hour and two-hourly thereafter for the first 48 postoperative hours. The
      cumulative morphine consumption during the first 24 and 48 postoperative hours were recorded.

      Platelet function assay was performed before and every 24 hrs. for the first three days after
      surgery. Cumulative intraoperative and postoperative blood loss and the number of transfused
      blood units were recorded. The presence of fracture non-union was reported.

      All patients were observed by an independent investigator during the study period for the
      presence of nausea, vomiting, gastritis, reflux esophagitis, headache, bleeding,
      bronchospasm, sweating, allergy, thrombocytopenia, bleeding, ecchymosis, or increases in
      liver transaminases.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: postoperative patient controlled morphine consumption
time frame: 24 hours and 48 hours after surgery
description: The cumulative morphine consumption during the first 24 and 48 postoperative hours were recorded.
measure: Quality of analgesia
time frame: every two hours for 24 hours after surgery
description: the use of visual analogue scale to assess the severity of postoperative pain (0 mm for no pain and100 mm for worst imaginable pain)
measure: platelet functions
time frame: daily after surgery for three days
measure: Bone non-union
time frame: for 3 months after surgery
measure: postoperative sedation
time frame: every two hours for 24 hours after surgery
description: four-point verbal rating scores (VRS): awake, drowsy, rousable or deep sleep),
measure: Nausea and vomiting
time frame: every two hours for 24 hours after surgery
description: nausea and vomiting (0: no nausea; 1: nausea no vomiting; 2: nausea and vomiting),
measure: Perioperative blood loss
time frame: Cumulative intraoperative and 24 hours after surgery
measure: Lornoxicam adverse effects
time frame: 48 hours after surgery
description: the presence of nausea, vomiting, gastritis, reflux esophagitis, headache, bleeding, bronchospasm, sweating, allergy, thrombocytopenia, bleeding, ecchymosis, or increases in liver transaminases.
arm group label: Placebo
arm group type: Placebo Comparator
description: The placebo group received 12 hourly boluses of 0.9% saline, followed by a constant infusion for 48 hrs after surgery.
arm group label: Scheduled
arm group type: Active Comparator
description: They received a 12 hourly boluses of lornoxicam followed by a constant infusion of 0.9% saline, for 48 hrs after surgery
arm group label: Continuous infusion
arm group type: Active Comparator
description: They received boluses of lornoxicam 0.8 mg/mL before induction of anaesthesia followed by a 12 hourly boluses of 0.9% saline and a constant infusion at 10 mL/h of lornoxicam 0.13 mg/mL, for 48 hrs. after surgery.
intervention type: Drug
intervention name: Placebo
description: The placebo group received 12 hourly 20-mL i.v. boluses of 0.9% saline starting 20 min before induction of anaesthesia, followed by a constant infusion at 10 mL/h, for 48 hrs after surgery.
arm group label: Placebo
intervention type: Drug
intervention name: Continuous infusion
description: The "continuous infusion" group received 20-mL i.v. boluses of lornoxicam 0.8 mg/mL starting 20 min before induction of anaesthesia followed by a 12 hourly 20-mL i.v. boluses of 0.9% saline and a constant infusion at 10 mL/h of lornoxicam 0.13 mg/mL, for 48 hrs. after surgery
arm group label: Continuous infusion
intervention type: Drug
intervention name: Scheduled
description: The "scheduled" group received an 12 hourly 20-mL i.v. boluses of lornoxicam 0.8 mg/mL starting 20 min before induction of anaesthesia followed by a constant infusion at 10 mL/h of 0.9% saline, for 48 hrs after surgery (supplied by Xefo, JPI, Saudi Arabia), starting 20 min before induction of anaesthesia.
arm group label: Scheduled
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Mohamed R El Tahan, MD
role: Principal Investigator
affiliation: College of Medicine, Mansoura University
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Mansoura University
investigator full name: Mohamed R El Tahan
investigator title: Associate Professor of Anesthesiology & SICU
mesh term: Fractures, Bone