<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/NCT04437888</url>
  </required_header>
  <id_info>
    <org_study_id>D20116</org_study_id>
    <secondary_id>STUDY02000376</secondary_id>
    <nct_id>NCT04437888</nct_id>
  </id_info>
  <brief_title>Intraoperative Ketamine for Patients Undergoing Total Joint Arthroplasty</brief_title>
  <official_title>Randomized Blinded, Placebo Controlled Trial Of Intrapoperative Ketamine For Patients Undergoing Total Joint</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dartmouth-Hitchcock Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dartmouth-Hitchcock Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prospective randomized double blinded, placebo controlled study that will evaluate the effect&#xD;
      of intra-operative ketamine administration on post-operative analgesic requirements and&#xD;
      self-reported pain in patients undergoing total hip and total knee arthroplasty who&#xD;
      demonstrate high levels of pain catastrophizing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pain management can be one of the most challenging aspects of care for total joint&#xD;
      arthroplasty patients. Poor post-operative pain control can lead to poor patient satisfaction&#xD;
      and functional outcomes. Moreover, prolonged post-operative opioid utilization for&#xD;
      post-operative pain is associated with substantial adverse sequelae. Identifying patients at&#xD;
      high risk for poor post-operative pain control, and implementing strategies to improve pain&#xD;
      management in this population is of utmost importance. One patient feature that has been&#xD;
      shown to reliably predict poor post-operative pain management is pain catastrophizing.&#xD;
      Currently available self-reported metrics such as the pain catastrophizing scale allow for&#xD;
      pre-operative identification of patients who exhibit high levels of pain catastrophizing.&#xD;
      Furthermore, there currently exist strategies which may effectively improve post-operative&#xD;
      pain management in this population. One such strategy is &quot;pre-emptive&quot; analgesia utilizing&#xD;
      ketamine administered at the time of surgery. Ketamine is commonly utilized in the treatment&#xD;
      of both acute and chronic pain, and is believed to reduce pain intensity through a complex&#xD;
      mechanism involving opioid receptors and excitatory neurotransmitters. It has been utilized&#xD;
      in a variety of surgical procedures and has consistently been shown to reduce acute&#xD;
      post-operative pain and analgesic consumption as long as 6 months after surgery, without a&#xD;
      significant incidence of medication related side effects. To date, no study has evaluated the&#xD;
      use of ketamine for total joint arthroplasty patients who demonstrate high levels of pain&#xD;
      catastrophizing. We aim to study the effect of intra-operative ketamine administration on&#xD;
      post-operative analgesic requirements and self-reported pain in patients undergoing total hip&#xD;
      and total knee arthroplasty who demonstrate high levels of pain catastrophizing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 14, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</primary_completion_date>
  <phase>Early Phase 1</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>
    <intervention_model_description>This study will be a randomized, prospective double-blind, placebo controlled trial to evaluate the efficacy of intra-operative ketamine administration in patients undergoing elective total hip or knee arthroplasty, who have high pain catastrophizing scores.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>The investigator, participant, research staff and medical provider will all be masked. The pharmacy will maintain the randomization and will provide the code at the conclusion of the study prior to data analysis.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Total Morphine consumption during the first 48 hours post surgery</measure>
    <time_frame>Daily for six weeks</time_frame>
    <description>Morphine consumption will be measured in a pain diary for 6- weeks post-surgical procedure. Decreased is morphine consumption will indicate effectiveness of ketamine administration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hip Disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS, JR.)</measure>
    <time_frame>Pre-operation, post-operation at 6 weeks, 12 weeks, and 6 months</time_frame>
    <description>six question questionnaire measuring joint specific pain and physical function, scored by summing the raw response (range 0-24) and then converting it to an interval score using the table provided below. The interval score ranges from 0 to 100 where 0 represents total hip disability and 100 represents perfect hip health.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Knee Disability and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR.)</measure>
    <time_frame>Pre-operation, post-operation at 6 weeks, 12 weeks, and 6 months</time_frame>
    <description>Seven question questionnaire measuring joint specific pain and physical functionscored by summing the raw response (range 0-28) and then converting it to an interval score using the table provided below. The interval score ranges from 0 to 100 where 0 represents total knee disability and 100 represents perfect knee health.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-Reported Outcomes Measurement Information System (PROMIS-10)</measure>
    <time_frame>Pre-operation, post-operation at 6 weeks, 12 weeks, and 6 months</time_frame>
    <description>patient-reported questionnaire in which the response options are presented as 5-point (as well as a single 11-point) rating scales. The results of the questions are used to calculate two summary scores: a Global Physical Health Score and a Global Mental Health score. The higher the score the healthier the subject is compared to the general population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Catastrophizing Scale (PCS)</measure>
    <time_frame>post-operation at 6 weeks, 12 weeks, and 6 months</time_frame>
    <description>The PCS is a 13 item scale, with each item rated on a 5-point scale: 0 (Not at all) to 4 (all the time). The PCS is broken into three subscales being magnification, rumination, and helplessness. The higher the score, the more catastrophizing thoughts are present.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Pain, Postoperative</condition>
  <condition>Arthroplasty Complications</condition>
  <arm_group>
    <arm_group_label>Racemic Ketamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>ketamine 0.5mg/kg bolus on induction of anesthesia and 10mcg/kg/min infusion initiated prior to incision and terminated at the completion of wound closure. Maximum ketamine dose will not exceed 500mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>saline in the same volume as the study drug, administered in the exact same format.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Ketamine versus saline placebo will be compared in order to evaluate the effects of Ketamine on patients that are pain catastrophizers</description>
    <arm_group_label>Racemic Ketamine</arm_group_label>
    <arm_group_label>Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        • Adults, 18 years and older, undergoing primary total hip arthroplasty or total knee&#xD;
        arthroplasty&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of intolerance or allergy to ketamine, either documented or self-reported.&#xD;
&#xD;
          -  History of increased intra-ocular pressure, uncontrolled hypertension, increased&#xD;
             intra-cranial pressure, psychosis.&#xD;
&#xD;
          -  Unable to provide consent.&#xD;
&#xD;
          -  Current incarceration.&#xD;
&#xD;
          -  Pregnant or breast feeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wayne E Moschetti, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dartmouth-Hitchcock Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Amy E. Hall, MS</last_name>
    <phone>603-653-3306</phone>
    <email>amy.e.hall@hitchcock.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Peter A DePalo, Sr., BS</last_name>
    <phone>603-653-0494</phone>
    <email>Peter.A.DePalo.Sr@hitchcock.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03766</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amy Hall, MS</last_name>
      <phone>603-653-3306</phone>
      <phone_ext>6036533306</phone_ext>
      <email>amy.e.hall@hitchcock.org</email>
    </contact>
    <investigator>
      <last_name>Wayne Moschetti, MD, MS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>August 24, 2022</last_update_submitted>
  <last_update_submitted_qc>August 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dartmouth-Hitchcock Medical Center</investigator_affiliation>
    <investigator_full_name>Wayne E. Moschetti</investigator_full_name>
    <investigator_title>Section Chief, Division of Adult Reconstructive Surgery</investigator_title>
  </responsible_party>
  <keyword>Ketamine</keyword>
  <keyword>Total Hip Replacement</keyword>
  <keyword>Total Knee Replacement</keyword>
  <keyword>Pain Catastrophizing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</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/NCT04437888
org study id: D20116
secondary id: STUDY02000376
nct id: NCT04437888
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Prospective randomized double blinded, placebo controlled study that will evaluate the effect
      of intra-operative ketamine administration on post-operative analgesic requirements and
      self-reported pain in patients undergoing total hip and total knee arthroplasty who
      demonstrate high levels of pain catastrophizing.
Pain management can be one of the most challenging aspects of care for total joint
      arthroplasty patients. Poor post-operative pain control can lead to poor patient satisfaction
      and functional outcomes. Moreover, prolonged post-operative opioid utilization for
      post-operative pain is associated with substantial adverse sequelae. Identifying patients at
      high risk for poor post-operative pain control, and implementing strategies to improve pain
      management in this population is of utmost importance. One patient feature that has been
      shown to reliably predict poor post-operative pain management is pain catastrophizing.
      Currently available self-reported metrics such as the pain catastrophizing scale allow for
      pre-operative identification of patients who exhibit high levels of pain catastrophizing.
      Furthermore, there currently exist strategies which may effectively improve post-operative
      pain management in this population. One such strategy is "pre-emptive" analgesia utilizing
      ketamine administered at the time of surgery. Ketamine is commonly utilized in the treatment
      of both acute and chronic pain, and is believed to reduce pain intensity through a complex
      mechanism involving opioid receptors and excitatory neurotransmitters. It has been utilized
      in a variety of surgical procedures and has consistently been shown to reduce acute
      post-operative pain and analgesic consumption as long as 6 months after surgery, without a
      significant incidence of medication related side effects. To date, no study has evaluated the
      use of ketamine for total joint arthroplasty patients who demonstrate high levels of pain
      catastrophizing. We aim to study the effect of intra-operative ketamine administration on
      post-operative analgesic requirements and self-reported pain in patients undergoing total hip
      and total knee arthroplasty who demonstrate high levels of pain catastrophizing.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This study will be a randomized, prospective double-blind, placebo controlled trial to evaluate the efficacy of intra-operative ketamine administration in patients undergoing elective total hip or knee arthroplasty, who have high pain catastrophizing scores.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: The investigator, participant, research staff and medical provider will all be masked. The pharmacy will maintain the randomization and will provide the code at the conclusion of the study prior to data analysis.
measure: Total Morphine consumption during the first 48 hours post surgery
time frame: Daily for six weeks
description: Morphine consumption will be measured in a pain diary for 6- weeks post-surgical procedure. Decreased is morphine consumption will indicate effectiveness of ketamine administration
measure: Hip Disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS, JR.)
time frame: Pre-operation, post-operation at 6 weeks, 12 weeks, and 6 months
description: six question questionnaire measuring joint specific pain and physical function, scored by summing the raw response (range 0-24) and then converting it to an interval score using the table provided below. The interval score ranges from 0 to 100 where 0 represents total hip disability and 100 represents perfect hip health.
measure: Knee Disability and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR.)
time frame: Pre-operation, post-operation at 6 weeks, 12 weeks, and 6 months
description: Seven question questionnaire measuring joint specific pain and physical functionscored by summing the raw response (range 0-28) and then converting it to an interval score using the table provided below. The interval score ranges from 0 to 100 where 0 represents total knee disability and 100 represents perfect knee health.
measure: Patient-Reported Outcomes Measurement Information System (PROMIS-10)
time frame: Pre-operation, post-operation at 6 weeks, 12 weeks, and 6 months
description: patient-reported questionnaire in which the response options are presented as 5-point (as well as a single 11-point) rating scales. The results of the questions are used to calculate two summary scores: a Global Physical Health Score and a Global Mental Health score. The higher the score the healthier the subject is compared to the general population.
measure: Pain Catastrophizing Scale (PCS)
time frame: post-operation at 6 weeks, 12 weeks, and 6 months
description: The PCS is a 13 item scale, with each item rated on a 5-point scale: 0 (Not at all) to 4 (all the time). The PCS is broken into three subscales being magnification, rumination, and helplessness. The higher the score, the more catastrophizing thoughts are present.
arm group label: Racemic Ketamine
arm group type: Active Comparator
description: ketamine 0.5mg/kg bolus on induction of anesthesia and 10mcg/kg/min infusion initiated prior to incision and terminated at the completion of wound closure. Maximum ketamine dose will not exceed 500mg
arm group label: Saline
arm group type: Placebo Comparator
description: saline in the same volume as the study drug, administered in the exact same format.
intervention type: Drug
intervention name: Ketamine
description: Ketamine versus saline placebo will be compared in order to evaluate the effects of Ketamine on patients that are pain catastrophizers
arm group label: Racemic Ketamine
arm group label: Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Wayne E Moschetti, MD, MS
role: Principal Investigator
affiliation: Dartmouth-Hitchcock Medical Center
last name: Amy E. Hall, MS
phone: 603-653-3306
email: amy.e.hall@hitchcock.org
last name: Peter A DePalo, Sr., BS
phone: 603-653-0494
email: Peter.A.DePalo.Sr@hitchcock.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dartmouth-Hitchcock Medical Center
investigator full name: Wayne E. Moschetti
investigator title: Section Chief, Division of Adult Reconstructive Surgery
mesh term: Pain, Postoperative
mesh term: Ketamine
sharing ipd: No