<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/NCT03823534</url>
  </required_header>
  <id_info>
    <org_study_id>28927</org_study_id>
    <nct_id>NCT03823534</nct_id>
  </id_info>
  <brief_title>Post-Op Pain Control for Prophylactic Intramedullary Nailing.</brief_title>
  <official_title>Post-Op Pain Control for Prophylactic Intramedullary Nailing.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Louis University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St. Louis University</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>
      Nationally, the opioid crisis has become a major epidemic with increasing mortality rates&#xD;
      each year. Orthopedic surgeons routinely prescribe narcotics instead of NSAIDs for post-op&#xD;
      pain control because of risk of delayed healing and nonunion due to NSAID use. Orthopedic&#xD;
      oncology, however, has a unique subset of patients that undergo prophylactic placement of&#xD;
      intramedullary femoral nails. Because no fracture is present, these patients do not rely on&#xD;
      inflammatory healing factors, allowing for post-op NSAID use. This study sets out to&#xD;
      determine the effect of post-op toradol use in addition to opioids compared to solely opioids&#xD;
      in patients undergoing prophylactic nailing of the femur.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nationally, the opioid crisis has become a major epidemic with increasing mortality rates&#xD;
      each year. Orthopedic surgeons routinely prescribe narcotics instead of NSAIDs for post-op&#xD;
      pain control because of risk of delayed healing and nonunion due to NSAID use. Orthopedic&#xD;
      oncology, however, has a unique subset of patients that undergo prophylactic placement of&#xD;
      intramedullary femoral nails, often due to bone metastases that increase risk for future&#xD;
      fractures. Because no fracture is present, these patients do not rely on inflammatory healing&#xD;
      factors, allowing for post-op NSAID use.&#xD;
&#xD;
      Recent literature has demonstrated the efficacy of multi-modal pain management in treating&#xD;
      post-op pain [1]. Currently, patients that undergo prophylactic intramedullary femur nail&#xD;
      placement at SLU are often treated with both narcotics and toradol, as long as they can&#xD;
      tolerate NSAIDs. However, the effect of toradol in addition to narcotics has not been&#xD;
      determined. This study sets out to determine the effect of post-op toradol use in addition to&#xD;
      opioids compared to solely opioids in patients undergoing prophylactic nailing of the femur.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 20, 2019</start_date>
  <completion_date type="Anticipated">October 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2024</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>
    <intervention_model_description>This study is a prospective, randomized, double-blind, placebo-controlled trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Both the patient and study investigators will be blinded. The hospital pharmacy will be unblinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Milligram Morphine Equivalent (MME) of Opioid Medications Utilized</measure>
    <time_frame>Post-op days 1-14</time_frame>
    <description>Measure the effect of post-op ketorolac on the concurrent use of opioid pain medications during post-op days 1-14 following prophylactic IMN of the femur compared to patients treated only with opioids.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient Reported Outcomes Measurement System (PROMIS) Pain Intensity Scale</measure>
    <time_frame>Up to six weeks post-op</time_frame>
    <description>Measure the effect of post-op ketorolac on PROMIS Pain Intensity score compared to the PROMIS of those that receive only opioids. Total scores are computed by summing the scores of the 3 individual questions. Possible scores range from 3-15 with higher values representing increasing pain over the previous 7 days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Single Assessment Numerical Evaluation (SANE)</measure>
    <time_frame>Up to six weeks post-op</time_frame>
    <description>Measure the effect of post-op ketorolac on SANE score compared to the SANE of those that receive only opioids. The score ranges from 0-100, with 100 representing the best possible perceived function of the limb and 0 the worst possible perceived function. There are no sub-scales.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numerical Rating Scale (NRS)</measure>
    <time_frame>Up to six weeks post-op</time_frame>
    <description>Measure the effect of post-op ketorolac on NRS score compared to the NRS of those that receive only opioids. Scores range from 0-10 with higher scores signifying increasing pain. There are no sub-scales.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Bone Metastases</condition>
  <condition>Lymphoma</condition>
  <condition>Multiple Myeloma</condition>
  <condition>Opioid Use</condition>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Experimental Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For the first 24 hours following surgery, patients younger than 65 years old will be administered a maximum of 120 mg/day bolus IV ketorolac (30 mg every 6 hours). Patients older than 65 years old or with history of advanced renal impairment will receive a maximum of 60 mg/day bolus IV ketorolac (15 mg every 6 hours). All patients may also be given acetaminophen 500 mg PO Q4 hours PRN for mild pain, oxycodone-acetaminophen 5-325 mg PO Q4 hours PRN for moderate- severe pain, and morphine IV PRN (or other opioid) for severe breakthrough pain while hospitalized. At discharge, they will be prescribed 1-2 hydrocodone-acetaminophen 5-325 mg Q4 hours, quantity 50. Those with preexisting liver disease will be prescribed the equivalent in oxycodone and will not receive acetaminophen for mild pain.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Following surgery, patients will be given acetaminophen 500 mg PO Q4 hours PRN for mild pain, oxycodone-acetaminophen 5-325 mg PO Q4 hours PRN for moderate-severe pain, and morphine IV PRN (or other opioid) for severe breakthrough pain while hospitalized. They will also be given a placebo injection of normal saline every 6 hours for the first 24 hours following surgery. At discharge, patients will be prescribed 1-2 hydrocodone-acetaminophen 5-325 mg Q4 hours PRN quantity 50, unless they have preexisting liver disease, in which case they will be prescribed the equivalent in oxycodone. They will not receive a nerve block.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketorolac</intervention_name>
    <description>IV Ketorolac to be given over the course of the first 24 hours after surgery. See arm/group description for further details.</description>
    <arm_group_label>Experimental Arm</arm_group_label>
    <other_name>Toradol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal saline</intervention_name>
    <description>An IV normal saline placebo prepared by the hospital pharmacy.</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetaminophen</intervention_name>
    <description>acetaminophen 500 mg PO Q4 hours PRN for mild pain</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Experimental Arm</arm_group_label>
    <other_name>Tylenol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxycodone Acetaminophen</intervention_name>
    <description>oxycodone-acetaminophen 5-325 mg PO Q4 hours PRN for moderate to severe pain</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Experimental Arm</arm_group_label>
    <other_name>Percocet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <description>morphine IV PRN (or other opioid) for severe breakthrough pain</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Experimental Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydrocodone/Acetaminophen</intervention_name>
    <description>At discharge, patients will be prescribed 1-2 hydrocodone-acetaminophen 5-325 mg Q4 hours. Those with preexisting liver disease will be prescribed the equivalent in oxycodone.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Experimental Arm</arm_group_label>
    <other_name>Norco</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxycodone</intervention_name>
    <description>Upon discharge, patients will be prescribed the equivalent of 1-2 hydrocodone 5mg Q4 hours upon should they have preexisting liver disease and are unable to consume acetaminophen.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Experimental Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Femoral Shaft or Neck bone lesion&#xD;
&#xD;
          2. 18 years old or greater&#xD;
&#xD;
          3. Plan to undergo prophylactic intramedullary nailing of one or both femurs&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concurrent pathologic fracture&#xD;
&#xD;
          2. History of advanced renal impairment&#xD;
&#xD;
          3. History of Peptic Ulcer Disease&#xD;
&#xD;
          4. History of NSAID or aspirin allergy&#xD;
&#xD;
          5. Concurrent chemotherapy regimen that prevents NSAID use&#xD;
&#xD;
          6. History of liver disease that precludes use of toradol&#xD;
&#xD;
          7. History of heart failure or cardiovascular disease&#xD;
&#xD;
          8. Pregnancy&#xD;
&#xD;
          9. History of opioid allergy that prevents used of opioids&#xD;
&#xD;
         10. Patients with coagulation disorders or those who require concomitant use of&#xD;
             anticoagulant or anti- platelet therapy during the treatment phase of the study.&#xD;
&#xD;
         11. Patients with acetaminophen allergies.&#xD;
&#xD;
         12. Current use of the medication probenecid&#xD;
&#xD;
         13. Current use of the medication Pentoxifylline&#xD;
&#xD;
         14. History of aspirin induced asthma.&#xD;
&#xD;
         15. History of coronary artery bypass graft&#xD;
&#xD;
         16. Known history of opioid dependence, abuse, or addiction.&#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>David Greenberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Louis University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>David Greenberg, MD</last_name>
    <phone>314-977-4147</phone>
    <email>david.greenberg@health.slu.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Allison Gruender, MSN</last_name>
    <phone>314-977-4106</phone>
    <email>allison.gruender@health.slu.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Saint Louis University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Allison Gruender, MSN</last_name>
      <phone>314-977-4106</phone>
      <email>allison.gruender@health.slu.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Cepeda MS, Carr DB, Miranda N, Diaz A, Silva C, Morales O. Comparison of morphine, ketorolac, and their combination for postoperative pain: results from a large, randomized, double-blind trial. Anesthesiology. 2005 Dec;103(6):1225-32. doi: 10.1097/00000542-200512000-00018.</citation>
    <PMID>16306736</PMID>
  </reference>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>January 29, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>December 6, 2022</last_update_submitted>
  <last_update_submitted_qc>December 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. Louis University</investigator_affiliation>
    <investigator_full_name>David Greenberg, MD;; Associate Professor</investigator_full_name>
    <investigator_title>Associate Professor, Orthopaedic Surgery</investigator_title>
  </responsible_party>
  <keyword>Toradol</keyword>
  <keyword>Ketorolac</keyword>
  <keyword>Prophylactic intramedullary nail</keyword>
  <keyword>bone metastases</keyword>
  <keyword>Opioid use</keyword>
  <keyword>post-operative pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Ketorolac</mesh_term>
    <mesh_term>Acetaminophen, hydrocodone drug combination</mesh_term>
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Oxycodone</mesh_term>
    <mesh_term>Hydrocodone</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/NCT03823534
org study id: 28927
nct id: NCT03823534
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Nationally, the opioid crisis has become a major epidemic with increasing mortality rates
      each year. Orthopedic surgeons routinely prescribe narcotics instead of NSAIDs for post-op
      pain control because of risk of delayed healing and nonunion due to NSAID use. Orthopedic
      oncology, however, has a unique subset of patients that undergo prophylactic placement of
      intramedullary femoral nails. Because no fracture is present, these patients do not rely on
      inflammatory healing factors, allowing for post-op NSAID use. This study sets out to
      determine the effect of post-op toradol use in addition to opioids compared to solely opioids
      in patients undergoing prophylactic nailing of the femur.
Nationally, the opioid crisis has become a major epidemic with increasing mortality rates
      each year. Orthopedic surgeons routinely prescribe narcotics instead of NSAIDs for post-op
      pain control because of risk of delayed healing and nonunion due to NSAID use. Orthopedic
      oncology, however, has a unique subset of patients that undergo prophylactic placement of
      intramedullary femoral nails, often due to bone metastases that increase risk for future
      fractures. Because no fracture is present, these patients do not rely on inflammatory healing
      factors, allowing for post-op NSAID use.

      Recent literature has demonstrated the efficacy of multi-modal pain management in treating
      post-op pain [1]. Currently, patients that undergo prophylactic intramedullary femur nail
      placement at SLU are often treated with both narcotics and toradol, as long as they can
      tolerate NSAIDs. However, the effect of toradol in addition to narcotics has not been
      determined. This study sets out to determine the effect of post-op toradol use in addition to
      opioids compared to solely opioids in patients undergoing prophylactic nailing of the femur.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This study is a prospective, randomized, double-blind, placebo-controlled trial.
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Both the patient and study investigators will be blinded. The hospital pharmacy will be unblinded.
measure: Milligram Morphine Equivalent (MME) of Opioid Medications Utilized
time frame: Post-op days 1-14
description: Measure the effect of post-op ketorolac on the concurrent use of opioid pain medications during post-op days 1-14 following prophylactic IMN of the femur compared to patients treated only with opioids.
measure: Patient Reported Outcomes Measurement System (PROMIS) Pain Intensity Scale
time frame: Up to six weeks post-op
description: Measure the effect of post-op ketorolac on PROMIS Pain Intensity score compared to the PROMIS of those that receive only opioids. Total scores are computed by summing the scores of the 3 individual questions. Possible scores range from 3-15 with higher values representing increasing pain over the previous 7 days.
measure: Single Assessment Numerical Evaluation (SANE)
time frame: Up to six weeks post-op
description: Measure the effect of post-op ketorolac on SANE score compared to the SANE of those that receive only opioids. The score ranges from 0-100, with 100 representing the best possible perceived function of the limb and 0 the worst possible perceived function. There are no sub-scales.
measure: Numerical Rating Scale (NRS)
time frame: Up to six weeks post-op
description: Measure the effect of post-op ketorolac on NRS score compared to the NRS of those that receive only opioids. Scores range from 0-10 with higher scores signifying increasing pain. There are no sub-scales.
arm group label: Experimental Arm
arm group type: Experimental
description: For the first 24 hours following surgery, patients younger than 65 years old will be administered a maximum of 120 mg/day bolus IV ketorolac (30 mg every 6 hours). Patients older than 65 years old or with history of advanced renal impairment will receive a maximum of 60 mg/day bolus IV ketorolac (15 mg every 6 hours). All patients may also be given acetaminophen 500 mg PO Q4 hours PRN for mild pain, oxycodone-acetaminophen 5-325 mg PO Q4 hours PRN for moderate- severe pain, and morphine IV PRN (or other opioid) for severe breakthrough pain while hospitalized. At discharge, they will be prescribed 1-2 hydrocodone-acetaminophen 5-325 mg Q4 hours, quantity 50. Those with preexisting liver disease will be prescribed the equivalent in oxycodone and will not receive acetaminophen for mild pain.
arm group label: Control
arm group type: Placebo Comparator
description: Following surgery, patients will be given acetaminophen 500 mg PO Q4 hours PRN for mild pain, oxycodone-acetaminophen 5-325 mg PO Q4 hours PRN for moderate-severe pain, and morphine IV PRN (or other opioid) for severe breakthrough pain while hospitalized. They will also be given a placebo injection of normal saline every 6 hours for the first 24 hours following surgery. At discharge, patients will be prescribed 1-2 hydrocodone-acetaminophen 5-325 mg Q4 hours PRN quantity 50, unless they have preexisting liver disease, in which case they will be prescribed the equivalent in oxycodone. They will not receive a nerve block.
intervention type: Drug
intervention name: Ketorolac
description: IV Ketorolac to be given over the course of the first 24 hours after surgery. See arm/group description for further details.
arm group label: Experimental Arm
other name: Toradol
intervention type: Drug
intervention name: Normal saline
description: An IV normal saline placebo prepared by the hospital pharmacy.
arm group label: Control
other name: Placebo
intervention type: Drug
intervention name: Acetaminophen
description: acetaminophen 500 mg PO Q4 hours PRN for mild pain
arm group label: Control
arm group label: Experimental Arm
other name: Tylenol
intervention type: Drug
intervention name: Oxycodone Acetaminophen
description: oxycodone-acetaminophen 5-325 mg PO Q4 hours PRN for moderate to severe pain
arm group label: Control
arm group label: Experimental Arm
other name: Percocet
intervention type: Drug
intervention name: Morphine
description: morphine IV PRN (or other opioid) for severe breakthrough pain
arm group label: Control
arm group label: Experimental Arm
intervention type: Drug
intervention name: Hydrocodone/Acetaminophen
description: At discharge, patients will be prescribed 1-2 hydrocodone-acetaminophen 5-325 mg Q4 hours. Those with preexisting liver disease will be prescribed the equivalent in oxycodone.
arm group label: Control
arm group label: Experimental Arm
other name: Norco
intervention type: Drug
intervention name: Oxycodone
description: Upon discharge, patients will be prescribed the equivalent of 1-2 hydrocodone 5mg Q4 hours upon should they have preexisting liver disease and are unable to consume acetaminophen.
arm group label: Control
arm group label: Experimental Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Greenberg, MD
role: Principal Investigator
affiliation: St. Louis University
last name: David Greenberg, MD
phone: 314-977-4147
email: david.greenberg@health.slu.edu
last name: Allison Gruender, MSN
phone: 314-977-4106
email: allison.gruender@health.slu.edu
facility: 
status: Recruiting
contact: 
country: United States
citation: Cepeda MS, Carr DB, Miranda N, Diaz A, Silva C, Morales O. Comparison of morphine, ketorolac, and their combination for postoperative pain: results from a large, randomized, double-blind trial. Anesthesiology. 2005 Dec;103(6):1225-32. doi: 10.1097/00000542-200512000-00018.
PMID: 16306736
responsible party type: Principal Investigator
investigator affiliation: St. Louis University
investigator full name: David Greenberg, MD;; Associate Professor
investigator title: Associate Professor, Orthopaedic Surgery
mesh term: Multiple Myeloma
mesh term: Neoplasm Metastasis
mesh term: Pain, Postoperative
mesh term: Acetaminophen
mesh term: Ketorolac
mesh term: Acetaminophen, hydrocodone drug combination
mesh term: Morphine
mesh term: Oxycodone
mesh term: Hydrocodone
sharing ipd: No