<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/NCT01667445</url>
  </required_header>
  <id_info>
    <org_study_id>102837</org_study_id>
    <nct_id>NCT01667445</nct_id>
  </id_info>
  <brief_title>Evaluation of the Use of Spinal Epimorph in Total Knee Arthroplasty</brief_title>
  <official_title>Determination of Effectiveness of Periarticular Local Infiltration When Compared to Spinal Epimorph for Analgesia in Total Knee Arthroplasty</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lawson Health Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lawson Health Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the contribution of spinal epimorph to patient's&#xD;
      perioperative pain management in Total Knee Arthroplasty (TKA). This study is designed to&#xD;
      determine whether spinal epimorph and its associated complications is a necessary addition to&#xD;
      provide adequate analgesia given the multimodal approach to pain management. It is&#xD;
      hypothesized that perioperative local infiltration with a cocktail of local and systemic&#xD;
      analgesics will provide equal analgesia to patients who are given both local infiltration and&#xD;
      spinal epimorph perioperatively.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a randomized control trial comparing two patient populations obtained from&#xD;
      patients who will receive a primary total knee arthroplasty at LHSC University Campus.&#xD;
      Patient participants will be recruited and consented from the arthroplasty clinic and from&#xD;
      the preadmit clinic at University Hospital. Both the patients and those measuring the primary&#xD;
      outcome, namely, visual pain scales will be blinded to the experimental treatment received.&#xD;
&#xD;
      Patients will be randomized to receive either a spinal with epimorph (150ug) or a spinal with&#xD;
      no epimorph at the time of their total hip arthroplasty. This is determined as a result of a&#xD;
      computer generated randomization within blocks of 10 (every 10 patients there will be an even&#xD;
      number of patients within each group). As each patient signs up they are given a consecutive&#xD;
      study number which will determine which group they are assigned to. Note should be made that&#xD;
      at the current time patients undergoing total joint arthroplasty may or may not receive&#xD;
      epimorph preoperatively depending on their anaesthesiologist (personal communication with Sue&#xD;
      Ganapathy) and so both treatment arms represent the current standard of care at LHSC. Again,&#xD;
      spinal epimorph is currently being administered for total joint replacement, irregardless of&#xD;
      whether or not this study is being done. It is an acceptable standard of care analgesic that&#xD;
      is available to each anesthetist should they choose to use it. Many choose to use it as they&#xD;
      feel it improves analgesia in patients undergoing total joint arthroplasty, which are&#xD;
      recognized as very painful procedures (especially total knees). This is no different that one&#xD;
      anesthetist preferring to use dilaudid for pain control and another choosing to use morphine.&#xD;
      Both are within accepted standard of care guidelines and it is up to the individual staff to&#xD;
      utilize the drug they feel is most beneficial. This decision is based on each individual&#xD;
      consultant's interpretation of the available literature as well as their personal practice&#xD;
      experience. I hope this justifies our study as we are not introducing any new treatment.&#xD;
      Patients will receive spinal epimorph whether or not we conduct this study. As such, no&#xD;
      formal study discontinuation rules are applicable. Both patient groups will receive medical&#xD;
      treatment as required around the time of their procedure.&#xD;
&#xD;
      Both groups of patients will receive standardized preoperative analgesia including gabapentin&#xD;
      (600mg), acetaminophen (975 mg) and naprosyn (500mg). Both groups will receive local&#xD;
      anaesthesia in the form of local infiltration of the wound with a previously studied cocktail&#xD;
      of morphine, ketoralac, epinephrine and ropivicaine. (3) Post operatively patients will&#xD;
      remain on PCA until post operative day one and then will be changed to a standardized oral&#xD;
      protocol including long and short acting narcotics on a PRN basis, acetaminophen (975 mg Q6h&#xD;
      x 48hrs and then on a PRN basis), naproxyn (500mg BID x 7 days) and gabapentin (300mg BID x 7&#xD;
      days).&#xD;
&#xD;
      Postoperatively visual analogue pain scales will be recorded at 6, 12, 18, 24, 36 and 48hrs&#xD;
      as well as at 1 week. Foley usage, oxygen usage, nausea/vomiting and use of antiemetics and&#xD;
      antipruritics will also be carefully documented. Both patient groups will receive the&#xD;
      standard post operative physiotherapy and will be discharged home with a prescription for the&#xD;
      narcotic or analgesics that were providing them with suitable analgesia during their hospital&#xD;
      stay.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</primary_completion_date>
  <phase>Phase 4</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>visual analogue scale for pain</measure>
    <time_frame>1 week post-operatively</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>patient report of nausea</measure>
    <time_frame>48hours post-operatively</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>patient report of pruritus</measure>
    <time_frame>48hours post-operatively</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>catheterization requirements</measure>
    <time_frame>48hours post-operatively</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">113</enrollment>
  <condition>Post-operative Pain</condition>
  <condition>Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>epimorph</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single dose administration of 150mcg epimorph</description>
  </arm_group>
  <arm_group>
    <arm_group_label>spinal analgesia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>spinal alone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epimorph</intervention_name>
    <description>Patient to receive 150ug of Epimorph with Spinal anaesthetic. Injection Cocktail includes: 10mg Morphine, 30mg Ketorolac, 3.5ug/ml (385ug total) of Ropivicaine, 2.5ug /ml (275ug total) Epinephrine with the remainder of the solution made of Normal Saline to a total volume of 110ml.</description>
    <arm_group_label>epimorph</arm_group_label>
    <other_name>morphine sulfate</other_name>
    <other_name>Duramorph PF</other_name>
    <other_name>MS Contin</other_name>
    <other_name>Roxano</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Spinal analgesia</intervention_name>
    <description>Patient to receive only Spinal anaesthetic (NO EPIMORPH). Injection Cocktail includes: 10mg Morphine, 30mg Ketorolac, 3.5ug/ml (385ug total) of Ropivicaine, 2.5ug /ml (275ug total) Epinephrine with the remainder of the solution made of Normal Saline to a total volume of 110ml.</description>
    <arm_group_label>spinal analgesia</arm_group_label>
    <other_name>Analgesia cocktail</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must receive a primary total knee arthroplasty&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to have a spinal anaesthetic&#xD;
&#xD;
          -  Intolerance to narcotic pain medication&#xD;
&#xD;
          -  Inability to use a Patient Controlled Analgesia&#xD;
&#xD;
          -  Revision total knee arthroplasty&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James L Howard, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>London Health Sciences Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital, London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <last_update_submitted>April 27, 2015</last_update_submitted>
  <last_update_submitted_qc>April 27, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 28, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Lawson Health Research Institute</investigator_affiliation>
    <investigator_full_name>James Howard</investigator_full_name>
    <investigator_title>Orthopaedic surgeon</investigator_title>
  </responsible_party>
  <keyword>total knee arthroplasty</keyword>
  <keyword>epimorph</keyword>
  <keyword>analgesia</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>Morphine</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/NCT01667445
org study id: 102837
nct id: NCT01667445
lead sponsor: 
has dmc: No
The purpose of this study is to determine the contribution of spinal epimorph to patient's
      perioperative pain management in Total Knee Arthroplasty (TKA). This study is designed to
      determine whether spinal epimorph and its associated complications is a necessary addition to
      provide adequate analgesia given the multimodal approach to pain management. It is
      hypothesized that perioperative local infiltration with a cocktail of local and systemic
      analgesics will provide equal analgesia to patients who are given both local infiltration and
      spinal epimorph perioperatively.
This will be a randomized control trial comparing two patient populations obtained from
      patients who will receive a primary total knee arthroplasty at LHSC University Campus.
      Patient participants will be recruited and consented from the arthroplasty clinic and from
      the preadmit clinic at University Hospital. Both the patients and those measuring the primary
      outcome, namely, visual pain scales will be blinded to the experimental treatment received.

      Patients will be randomized to receive either a spinal with epimorph (150ug) or a spinal with
      no epimorph at the time of their total hip arthroplasty. This is determined as a result of a
      computer generated randomization within blocks of 10 (every 10 patients there will be an even
      number of patients within each group). As each patient signs up they are given a consecutive
      study number which will determine which group they are assigned to. Note should be made that
      at the current time patients undergoing total joint arthroplasty may or may not receive
      epimorph preoperatively depending on their anaesthesiologist (personal communication with Sue
      Ganapathy) and so both treatment arms represent the current standard of care at LHSC. Again,
      spinal epimorph is currently being administered for total joint replacement, irregardless of
      whether or not this study is being done. It is an acceptable standard of care analgesic that
      is available to each anesthetist should they choose to use it. Many choose to use it as they
      feel it improves analgesia in patients undergoing total joint arthroplasty, which are
      recognized as very painful procedures (especially total knees). This is no different that one
      anesthetist preferring to use dilaudid for pain control and another choosing to use morphine.
      Both are within accepted standard of care guidelines and it is up to the individual staff to
      utilize the drug they feel is most beneficial. This decision is based on each individual
      consultant's interpretation of the available literature as well as their personal practice
      experience. I hope this justifies our study as we are not introducing any new treatment.
      Patients will receive spinal epimorph whether or not we conduct this study. As such, no
      formal study discontinuation rules are applicable. Both patient groups will receive medical
      treatment as required around the time of their procedure.

      Both groups of patients will receive standardized preoperative analgesia including gabapentin
      (600mg), acetaminophen (975 mg) and naprosyn (500mg). Both groups will receive local
      anaesthesia in the form of local infiltration of the wound with a previously studied cocktail
      of morphine, ketoralac, epinephrine and ropivicaine. (3) Post operatively patients will
      remain on PCA until post operative day one and then will be changed to a standardized oral
      protocol including long and short acting narcotics on a PRN basis, acetaminophen (975 mg Q6h
      x 48hrs and then on a PRN basis), naproxyn (500mg BID x 7 days) and gabapentin (300mg BID x 7
      days).

      Postoperatively visual analogue pain scales will be recorded at 6, 12, 18, 24, 36 and 48hrs
      as well as at 1 week. Foley usage, oxygen usage, nausea/vomiting and use of antiemetics and
      antipruritics will also be carefully documented. Both patient groups will receive the
      standard post operative physiotherapy and will be discharged home with a prescription for the
      narcotic or analgesics that were providing them with suitable analgesia during their hospital
      stay.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: visual analogue scale for pain
time frame: 1 week post-operatively
measure: patient report of nausea
time frame: 48hours post-operatively
measure: patient report of pruritus
time frame: 48hours post-operatively
measure: catheterization requirements
time frame: 48hours post-operatively
arm group label: epimorph
arm group type: Experimental
description: single dose administration of 150mcg epimorph
arm group label: spinal analgesia
arm group type: Active Comparator
description: spinal alone
intervention type: Drug
intervention name: Epimorph
description: Patient to receive 150ug of Epimorph with Spinal anaesthetic. Injection Cocktail includes: 10mg Morphine, 30mg Ketorolac, 3.5ug/ml (385ug total) of Ropivicaine, 2.5ug /ml (275ug total) Epinephrine with the remainder of the solution made of Normal Saline to a total volume of 110ml.
arm group label: epimorph
other name: morphine sulfate
other name: Duramorph PF
other name: MS Contin
other name: Roxano
intervention type: Drug
intervention name: Spinal analgesia
description: Patient to receive only Spinal anaesthetic (NO EPIMORPH). Injection Cocktail includes: 10mg Morphine, 30mg Ketorolac, 3.5ug/ml (385ug total) of Ropivicaine, 2.5ug /ml (275ug total) Epinephrine with the remainder of the solution made of Normal Saline to a total volume of 110ml.
arm group label: spinal analgesia
other name: Analgesia cocktail
criteria: 
gender: All
minimum age: 40 Years
maximum age: 90 Years
healthy volunteers: No
last name: James L Howard, MD
role: Principal Investigator
affiliation: London Health Sciences Centre
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Lawson Health Research Institute
investigator full name: James Howard
investigator title: Orthopaedic surgeon
mesh term: Pain, Postoperative
mesh term: Morphine