<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/NCT03834129</url>
  </required_header>
  <id_info>
    <org_study_id>2018/08</org_study_id>
    <nct_id>NCT03834129</nct_id>
  </id_info>
  <brief_title>Dexmedetomidine Intra Venous Arthroplasty</brief_title>
  <acronym>DIVA</acronym>
  <official_title>Interest of Intravenous Dexmedetomidine (Dexdor®) in the Knee Replacement Surgery Performed Under Locoregional Anesthesia: a Randomized, Double Blind, Controlled Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CMC Ambroise Paré</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CMC Ambroise Paré</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Intravenous dexmedetomidine is a drug used in reanimation with sedative, anxiolytic and&#xD;
      sympatholytic properties. Recent studies showed useful properties for anaesthesia : decrease&#xD;
      of morphine consumption after a various type of surgery, sedative effect on patients under&#xD;
      regional anaesthesia, prolongation of central or peripheral regional block. Dose-ranging&#xD;
      study for intravenous dexmedetomidine showed that 2 µg/kg is an effective dose to prolong&#xD;
      interscalene block. This study aims to determine if intravenous dexmedetomidine at 2 µg/kg&#xD;
      allows a longer analgesic duration after a quadri-block (femoral, subgluteal sciatic,&#xD;
      obturator and alateral cutaneous nerve blocks) with ropivacaine 0.32% for total knee&#xD;
      replacement under regional anaesthesia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, randomized, double-blind controlled trial with two parallel groups.&#xD;
      All patients undergoing total knee arthroplasty under regional anaesthesia and sedation will&#xD;
      be screened for inclusion in the protocol. In the pre-anaesthesia room, after the&#xD;
      implementation of classical monitoring with an oxygen mask and a peripheral venous catheter,&#xD;
      all patients will receive an antibioprophylaxy according to SFAR recommendations and&#xD;
      injection of 10 mg of IV dexamethasone.&#xD;
&#xD;
      The patients will be then randomized in 2 groups:&#xD;
&#xD;
        -  Dexmedetomidine group (Dex group) : Two administrations of 1 microg/kg of Dexdor® in 250&#xD;
           ml of sodium chloride during 30 min. The first injection will be performed in the&#xD;
           pre-anaesthesia unit and the second in the operating room with a free interval of 60 min&#xD;
           between the beginning of the 2 injections.&#xD;
&#xD;
        -  Control group : Two administrations of 250 ml of sodium chloride during 30 min according&#xD;
           to the same former recommendations.&#xD;
&#xD;
      Under ultrasonography guidance and with in-plan technic, a quadri-block (femoral, sciatic&#xD;
      subgluteal, obturator and lateral cutaneous nerve blocks) with a maximum of 225 mg of&#xD;
      ropivacaine diluted in 70 ml of sodium chloride (ropivacaine 0.32 %) will be performed. If&#xD;
      needed, sedation with 5 µg of sufentanil and 1 to 2 mg of midazolam will be performed before&#xD;
      regional anaesthesia.&#xD;
&#xD;
      In the operating room, under close monitoring, the patients will receive a bolus of Ketamine&#xD;
      0.3 mg/kg and a propofol bolus of 0.3 mg/kg followed by a continuous infusion if needed. The&#xD;
      total dose of propofol used for sedation, conversion to general anaesthesia or any&#xD;
      complications concerning anaesthesia or dexmedetomidine (hypotension, bradycardia,&#xD;
      arrhythmia, advance cardiac block) will be collected. Postoperative analgesia will be reached&#xD;
      with IV 1 g paracetamol and 100 mg ketoprofen starting during surgery and following in the&#xD;
      surgical ward by oral paracetamol 1 g / 6 h and oral ibuprofen 400 mg / 8 h. In post&#xD;
      anaesthesia care unit all the patients will have oxycodone titration if pain VRS (verbal&#xD;
      rating scale) &gt;3 and oxycodone 10 mg/ 4 h in the surgical ward if pain VRS (verbal rating&#xD;
      scale) &gt;3.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 13, 2019</start_date>
  <completion_date type="Actual">January 11, 2020</completion_date>
  <primary_completion_date type="Actual">January 11, 2020</primary_completion_date>
  <phase>Phase 3</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>Evaluate the effect of dexmedetomidine infusion 2 μg/kg in pre-anesthesia and operative room, on duration of postoperative analgesia after a knee arthroplasty performed under locoregional anesthesia.</measure>
    <time_frame>48 hours</time_frame>
    <description>Duration of analgesia defined as the time between the performance of regional anesthesia and the first dose of rescue analgesia with opioides.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of hypotension or bradycardia Events.</measure>
    <time_frame>48 hours</time_frame>
    <description>Number of complications due to dexmedetomidine (hypotension or bradycardia episodes)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximal postoperative pain.</measure>
    <time_frame>48 hours</time_frame>
    <description>Pain VRS verbal rating scale ranging from 0 to 10 (0=no pain, 10=worst possible pain)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative opioids morphine consumption.</measure>
    <time_frame>48 hours</time_frame>
    <description>Postoperative cumulated dose of oxynorm (mg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose of hypnotic drug during surgery.</measure>
    <time_frame>4 hours</time_frame>
    <description>Total amount of propofol (mg) administered during surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ability to walk</measure>
    <time_frame>Days 0, 1 and 2</time_frame>
    <description>Distance &lt; 50 m or &gt; 50 m</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quadricep mobilization</measure>
    <time_frame>Days 0, 1 and 2</time_frame>
    <description>0 : paralysis ; 1 : paresis ; 2 : normal contraction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Foot elevator muscle mobilization</measure>
    <time_frame>Days 0, 1 and 2</time_frame>
    <description>0 : paralysis ; 1 : paresis ; 2 : normal contraction</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">94</enrollment>
  <condition>Primary Total Knee Arthroplasty</condition>
  <arm_group>
    <arm_group_label>(Dex group) intravenous infusion of dexmedetomidine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pre-anesthetic and per-operative intravenous infusions of dexmedetomidine 1µg/kg in 250ml of sodium chloride 0.9%</description>
  </arm_group>
  <arm_group>
    <arm_group_label>(Control group) intravenous infusion of physiological serum</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Pre-anesthetic and per-operative intravenous infusions of 250ml of sodium chloride 0.9%</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexmedetomidine</intervention_name>
    <description>Two administrations, before anesthesia and during surgery, by intravenous infusion of dexmedetomidine 1 μg/kg in 250 ml of physiological serum for 30 minutes</description>
    <arm_group_label>(Dex group) intravenous infusion of dexmedetomidine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sodium chloride 0.9%</intervention_name>
    <description>Two administrations, before anesthesia and during surgery, by intravenous infusion of 250 ml of physiological serum for 30 minutes</description>
    <arm_group_label>(Control group) intravenous infusion of physiological serum</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years and older&#xD;
&#xD;
          -  Patients undergoing elective total knee arthroplasty&#xD;
&#xD;
          -  Consent for participation&#xD;
&#xD;
          -  Affiliation to the french social security system&#xD;
&#xD;
          -  For women of child bearing potential without contraception, beta-HCG negative result&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic pain syndrome requiring preoperative morphine use (class 3)&#xD;
&#xD;
          -  Hypersensitivity to dexmedetomidine&#xD;
&#xD;
          -  Allergy to nonsteroidal anti-inflammatory drugs&#xD;
&#xD;
          -  Contraindication for locoregional anesthesia&#xD;
&#xD;
          -  Patient wishing a general anesthesia&#xD;
&#xD;
          -  Weight&gt;100 kg, obstructive sleep apnea syndrome or gastrooesophageal reflux&#xD;
             complicating the sedation with spontaneous ventilation&#xD;
&#xD;
          -  Known acute ischemic disease&#xD;
&#xD;
          -  Severe liver failure&#xD;
&#xD;
          -  Uncontrolled low blood pressure&#xD;
&#xD;
          -  Heart rate &lt; 60 bpm&#xD;
&#xD;
          -  Advanced cardiac block (Level 2 or 3) except if pacemaker&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Communication difficulties or neuropsychiatric disorder&#xD;
&#xD;
          -  Patients under protection of the adults (guardianship, curators or safeguard of&#xD;
             justice)&#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>Clinique Médipôle Garonne</name>
      <address>
        <city>Toulouse</city>
        <state>Haute-Garonne</state>
        <zip>31036</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>February 5, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 7, 2019</study_first_posted>
  <last_update_submitted>February 5, 2020</last_update_submitted>
  <last_update_submitted_qc>February 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexmedetomidine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03834129
org study id: 2018/08
nct id: NCT03834129
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Intravenous dexmedetomidine is a drug used in reanimation with sedative, anxiolytic and
      sympatholytic properties. Recent studies showed useful properties for anaesthesia : decrease
      of morphine consumption after a various type of surgery, sedative effect on patients under
      regional anaesthesia, prolongation of central or peripheral regional block. Dose-ranging
      study for intravenous dexmedetomidine showed that 2 µg/kg is an effective dose to prolong
      interscalene block. This study aims to determine if intravenous dexmedetomidine at 2 µg/kg
      allows a longer analgesic duration after a quadri-block (femoral, subgluteal sciatic,
      obturator and alateral cutaneous nerve blocks) with ropivacaine 0.32% for total knee
      replacement under regional anaesthesia.
This is a prospective, randomized, double-blind controlled trial with two parallel groups.
      All patients undergoing total knee arthroplasty under regional anaesthesia and sedation will
      be screened for inclusion in the protocol. In the pre-anaesthesia room, after the
      implementation of classical monitoring with an oxygen mask and a peripheral venous catheter,
      all patients will receive an antibioprophylaxy according to SFAR recommendations and
      injection of 10 mg of IV dexamethasone.

      The patients will be then randomized in 2 groups:

        -  Dexmedetomidine group (Dex group) : Two administrations of 1 microg/kg of Dexdor® in 250
           ml of sodium chloride during 30 min. The first injection will be performed in the
           pre-anaesthesia unit and the second in the operating room with a free interval of 60 min
           between the beginning of the 2 injections.

        -  Control group : Two administrations of 250 ml of sodium chloride during 30 min according
           to the same former recommendations.

      Under ultrasonography guidance and with in-plan technic, a quadri-block (femoral, sciatic
      subgluteal, obturator and lateral cutaneous nerve blocks) with a maximum of 225 mg of
      ropivacaine diluted in 70 ml of sodium chloride (ropivacaine 0.32 %) will be performed. If
      needed, sedation with 5 µg of sufentanil and 1 to 2 mg of midazolam will be performed before
      regional anaesthesia.

      In the operating room, under close monitoring, the patients will receive a bolus of Ketamine
      0.3 mg/kg and a propofol bolus of 0.3 mg/kg followed by a continuous infusion if needed. The
      total dose of propofol used for sedation, conversion to general anaesthesia or any
      complications concerning anaesthesia or dexmedetomidine (hypotension, bradycardia,
      arrhythmia, advance cardiac block) will be collected. Postoperative analgesia will be reached
      with IV 1 g paracetamol and 100 mg ketoprofen starting during surgery and following in the
      surgical ward by oral paracetamol 1 g / 6 h and oral ibuprofen 400 mg / 8 h. In post
      anaesthesia care unit all the patients will have oxycodone titration if pain VRS (verbal
      rating scale) >3 and oxycodone 10 mg/ 4 h in the surgical ward if pain VRS (verbal rating
      scale) >3.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Evaluate the effect of dexmedetomidine infusion 2 μg/kg in pre-anesthesia and operative room, on duration of postoperative analgesia after a knee arthroplasty performed under locoregional anesthesia.
time frame: 48 hours
description: Duration of analgesia defined as the time between the performance of regional anesthesia and the first dose of rescue analgesia with opioides.
measure: Incidence of hypotension or bradycardia Events.
time frame: 48 hours
description: Number of complications due to dexmedetomidine (hypotension or bradycardia episodes)
measure: Maximal postoperative pain.
time frame: 48 hours
description: Pain VRS verbal rating scale ranging from 0 to 10 (0=no pain, 10=worst possible pain)
measure: Postoperative opioids morphine consumption.
time frame: 48 hours
description: Postoperative cumulated dose of oxynorm (mg)
measure: Dose of hypnotic drug during surgery.
time frame: 4 hours
description: Total amount of propofol (mg) administered during surgery
measure: Ability to walk
time frame: Days 0, 1 and 2
description: Distance < 50 m or > 50 m
measure: Quadricep mobilization
time frame: Days 0, 1 and 2
description: 0 : paralysis ; 1 : paresis ; 2 : normal contraction
measure: Foot elevator muscle mobilization
time frame: Days 0, 1 and 2
description: 0 : paralysis ; 1 : paresis ; 2 : normal contraction
arm group label: (Dex group) intravenous infusion of dexmedetomidine
arm group type: Experimental
description: Pre-anesthetic and per-operative intravenous infusions of dexmedetomidine 1µg/kg in 250ml of sodium chloride 0.9%
arm group label: (Control group) intravenous infusion of physiological serum
arm group type: Placebo Comparator
description: Pre-anesthetic and per-operative intravenous infusions of 250ml of sodium chloride 0.9%
intervention type: Drug
intervention name: Dexmedetomidine
description: Two administrations, before anesthesia and during surgery, by intravenous infusion of dexmedetomidine 1 μg/kg in 250 ml of physiological serum for 30 minutes
arm group label: (Dex group) intravenous infusion of dexmedetomidine
intervention type: Drug
intervention name: sodium chloride 0.9%
description: Two administrations, before anesthesia and during surgery, by intravenous infusion of 250 ml of physiological serum for 30 minutes
arm group label: (Control group) intravenous infusion of physiological serum
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: France
responsible party type: Sponsor
mesh term: Dexmedetomidine
sharing ipd: No