<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/NCT02967172</url>
  </required_header>
  <id_info>
    <org_study_id>201608737</org_study_id>
    <nct_id>NCT02967172</nct_id>
  </id_info>
  <brief_title>Efficacy of Multimodal Periarticular Injections in Operatively Treated Ankle Fractures</brief_title>
  <official_title>Efficacy of Multimodal Periarticular Injections in Operatively Treated Ankle Fractures: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kyle Hancock</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Iowa</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the efficacy and safety of a peri-articular&#xD;
      multimodal injection for post-operative pain control following operative management of&#xD;
      closed, rotational ankle fractures. Enrolled subjects will be randomized to either receive or&#xD;
      not receive intra-operative injections in addition to standard opioid analgesic regimens.&#xD;
      Patients will be treated with standard of care surgical techniques by the treating&#xD;
      orthopaedic surgeon for the patient's specific fracture pattern. The patients randomized into&#xD;
      the injection cohort will receive a 25cc intra-operative injection with 200 mg ropivacaine,&#xD;
      0.6 mg epinephrine, 5 mg and morphine into the local superficial and deep peri-incisional&#xD;
      tissues while under general anesthesia. Total post-operative opioid consumption expressed in&#xD;
      morphine equivalent dose will be recorded, including IV and oral opioids. Time in hours from&#xD;
      operation conclusion to discharge and discharge disposition (to where the patient is&#xD;
      discharged) will also be recorded. Post-operative pain scores will be assessed and recorded&#xD;
      in the immediate post-operative period and every 4 hours subsequently until the patient is&#xD;
      discharged. Medication related side effects will be monitored. The investigators hypothesize&#xD;
      that the injection cohort will have reduced pain scores, lower narcotic requirements, shorter&#xD;
      length of stay, and be more likely to discharge to home following surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Periarticular fractures (bone breaks extending into the joint surface) treated by orthopaedic&#xD;
      surgeons are associated with significant pain in the post-operative period, often requiring&#xD;
      high doses of opioid analgesics. In recent years, the high risk of misuse, abuse, and death&#xD;
      associated with prescription opioid use has become increasingly evident.&#xD;
&#xD;
      Although physicians are being advised to avoid administration of opioid prescriptions,&#xD;
      alternative pain management options are limited. Currently, there is a need to investigate&#xD;
      different pain management models in order to provide safe and effective pain relief during&#xD;
      the post-operative period. The investigators aim to evaluate the effectiveness of&#xD;
      peri-incisional multimodal injections as an alternative post-operative pain control method in&#xD;
      orthopaedic trauma patients with operative ankle fractures. Approximately 200 patients will&#xD;
      be randomized to either receive or not receive intra-operative injections in addition to&#xD;
      standard opioid analgesic regimens. Post-operative pain management outcomes will be assessed&#xD;
      and compared between the 2 study groups to determine effectiveness of the injections. The&#xD;
      proposed study will build upon related work to advance post-operative pain control regimens&#xD;
      in orthopaedic surgery. Goals include the reduction of unnecessary patient suffering,&#xD;
      reliance on opioids, and length of stay, while improving patient experience. These aims will&#xD;
      be accomplished through the expansion of currently used multimodal periarticular injections&#xD;
      from populations undergoing elective surgery to orthopaedic trauma patients with rotational&#xD;
      ankle fractures.&#xD;
&#xD;
      The study design is a prospective, double-blinded, randomized controlled trial. Patients&#xD;
      included in the study will be randomly assigned to one of two treatment groups:&#xD;
      intra-operative multimodal periarticular injection or control (no injection). The&#xD;
      peri-incisional injection will consist of ropivacaine, epinephrine, and morphine. All&#xD;
      pharmacologic agents in the anesthetic cocktail are FDA approved and have been previously&#xD;
      used in combination during other types of orthopaedic surgeries.&#xD;
&#xD;
      All patients included in the study will receive standard post-operative opioid analgesic&#xD;
      regimens, administered 'per needed', regardless of their assigned treatment group per study&#xD;
      protocol. ≥ 40 patients will be randomly assigned to each group. The patients enrolled in the&#xD;
      investigation as well as health care professionals performing post-operative assessments and&#xD;
      collecting data will be blinded to treatment allocation. The feasibility of multimodal&#xD;
      peri-incisional injections is supported by their current efficacy in populations undergoing&#xD;
      elective orthopedic surgeries. These injections may be equally effective at reducing pain&#xD;
      compared to regional anesthesia with continuous infusions, and single-shot nerve blocks.&#xD;
&#xD;
      The investigators hypothesize that the injection cohort will have reduced pain scores, lower&#xD;
      narcotic requirements, shorter length of stay, and be more likely to discharge to home&#xD;
      following surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2016</start_date>
  <completion_date type="Actual">September 21, 2018</completion_date>
  <primary_completion_date type="Actual">September 21, 2018</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>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Post-operative Visual Analog Pain Scores</measure>
    <time_frame>Immediately following surgery, then every 4 hours following surgery for 7 days. Patients will be re-evaluated every 3 months for up to 1 year post-operation</time_frame>
    <description>Patients will describe their current level of comfort on a 10 point scale while at rest. Zero corresponds to &quot;no pain&quot; and ten corresponds to &quot;the most extreme possible pain.&quot; Visual analog scores will be collected by nursing staff who are blinded to the treatment allocation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total post-operative narcotic consumption</measure>
    <time_frame>From immediately following surgery to 90 days after.</time_frame>
    <description>Total post-operative opioid consumption expressed in morphine equivalent dose will be recorded, including IV and oral opioids.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-operative length of stay</measure>
    <time_frame>From immediately following surgery to 90 days after.</time_frame>
    <description>Number of days in the hospital following surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type of facility patient will go to after hospital discharge</measure>
    <time_frame>From immediately following surgery to 90 days after.</time_frame>
    <description>e.g. Skilled Nursing Facility, Rehabilitation Center, Home. The location is always established prior to discharging a patient from the hospital. This information can be found on the patient's electronic medical record.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Medication-related side effects</measure>
    <time_frame>From immediately following surgery to 7 days after.</time_frame>
    <description>Patients will be monitored by nursing personnel for medication side effects related to ropivacaine toxicity including blurred vision, hearing problems, transient peripheral paralysis, dizziness, convulsion, uncontrolled muscle contraction, hypotension, bradycardia, and new onset arrhythmia.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Pain, Postoperative</condition>
  <condition>Ankle Fractures</condition>
  <arm_group>
    <arm_group_label>Peri-incisional injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single, 25 cc multimodal analgesic cocktail will be injected following completion of ankle fracture fixation/instrumentation while the patient remains under general anesthesia and prior to skin closure. The injection will be administered as such:&#xD;
20 mL injected into the peri-incisional soft tissues in a circumferential fashion&#xD;
5mL injected into the ankle joint This cocktail includes 200 mg of 0.8% ropivacaine, 0.6 mg of epinephrine, 5 mg of morphine sulfate, and sodium chloride solution. All infiltrations will be completed with a blunt trochar to minimize the risk of intravascular injection.&#xD;
Interventions:&#xD;
Drug: Ropivacaine Drug: Epinephrine Drug: Morphine Drug: 0.9% sodium chloride solution Following surgery, patients in the treatment and non-treatment groups will both be provided with the same intravenous (patient-controlled analgesia) and oral pain medications scheduled &quot;per needed&quot;.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Ankle fracture fixation/instrumentation will be completed per the standard of care. No peri-incisional injection will be completed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ropivacaine</intervention_name>
    <arm_group_label>Peri-incisional injection</arm_group_label>
    <other_name>Naropin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epinephrine</intervention_name>
    <arm_group_label>Peri-incisional injection</arm_group_label>
    <other_name>Adrenalin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <arm_group_label>Peri-incisional injection</arm_group_label>
    <other_name>Duramorph</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.9% sodium chloride solution</intervention_name>
    <arm_group_label>Peri-incisional injection</arm_group_label>
    <other_name>0.9% normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All consenting patients 18 years of age and older with operative, closed, rotational&#xD;
             ankle fractures treated with internal fixation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with any of the following:&#xD;
&#xD;
               -  Allergy or medical contraindication to any of the study medications&#xD;
&#xD;
               -  Pregnant women&#xD;
&#xD;
               -  Diagnosed dementia&#xD;
&#xD;
               -  Preexisting opioid or illicit drug dependency&#xD;
&#xD;
               -  Major neuromuscular deficit&#xD;
&#xD;
               -  Severe systemic disorder (heart failure, respiratory failure, kidney failure,&#xD;
                  liver failure, or a clotting disorder)&#xD;
&#xD;
               -  Major head trauma&#xD;
&#xD;
               -  Concomitant distracting injury&#xD;
&#xD;
               -  Other surgical intervention in the study period (1 week)&#xD;
&#xD;
               -  Revision operations&#xD;
&#xD;
               -  Insists to receive peripheral nerve blocks for surgical anesthesia&#xD;
&#xD;
               -  Refusal to participate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kyle Hancock, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Resident Physician</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Iowa Hospitals and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>October 27, 2016</study_first_submitted>
  <study_first_submitted_qc>November 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <last_update_submitted>November 20, 2018</last_update_submitted>
  <last_update_submitted_qc>November 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Iowa</investigator_affiliation>
    <investigator_full_name>Kyle Hancock</investigator_full_name>
    <investigator_title>Resident Physician</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
    <mesh_term>Fractures, Bone</mesh_term>
    <mesh_term>Ankle Fractures</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epinephrine</mesh_term>
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Ropivacaine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>July 1, 2021</submitted>
    <returned>July 22, 2021</returned>
    <submitted>June 28, 2022</submitted>
    <returned>July 21, 2022</returned>
  </pending_results>
  <!-- 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/NCT02967172
org study id: 201608737
nct id: NCT02967172
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
The purpose of this study is to determine the efficacy and safety of a peri-articular
      multimodal injection for post-operative pain control following operative management of
      closed, rotational ankle fractures. Enrolled subjects will be randomized to either receive or
      not receive intra-operative injections in addition to standard opioid analgesic regimens.
      Patients will be treated with standard of care surgical techniques by the treating
      orthopaedic surgeon for the patient's specific fracture pattern. The patients randomized into
      the injection cohort will receive a 25cc intra-operative injection with 200 mg ropivacaine,
      0.6 mg epinephrine, 5 mg and morphine into the local superficial and deep peri-incisional
      tissues while under general anesthesia. Total post-operative opioid consumption expressed in
      morphine equivalent dose will be recorded, including IV and oral opioids. Time in hours from
      operation conclusion to discharge and discharge disposition (to where the patient is
      discharged) will also be recorded. Post-operative pain scores will be assessed and recorded
      in the immediate post-operative period and every 4 hours subsequently until the patient is
      discharged. Medication related side effects will be monitored. The investigators hypothesize
      that the injection cohort will have reduced pain scores, lower narcotic requirements, shorter
      length of stay, and be more likely to discharge to home following surgery.
Periarticular fractures (bone breaks extending into the joint surface) treated by orthopaedic
      surgeons are associated with significant pain in the post-operative period, often requiring
      high doses of opioid analgesics. In recent years, the high risk of misuse, abuse, and death
      associated with prescription opioid use has become increasingly evident.

      Although physicians are being advised to avoid administration of opioid prescriptions,
      alternative pain management options are limited. Currently, there is a need to investigate
      different pain management models in order to provide safe and effective pain relief during
      the post-operative period. The investigators aim to evaluate the effectiveness of
      peri-incisional multimodal injections as an alternative post-operative pain control method in
      orthopaedic trauma patients with operative ankle fractures. Approximately 200 patients will
      be randomized to either receive or not receive intra-operative injections in addition to
      standard opioid analgesic regimens. Post-operative pain management outcomes will be assessed
      and compared between the 2 study groups to determine effectiveness of the injections. The
      proposed study will build upon related work to advance post-operative pain control regimens
      in orthopaedic surgery. Goals include the reduction of unnecessary patient suffering,
      reliance on opioids, and length of stay, while improving patient experience. These aims will
      be accomplished through the expansion of currently used multimodal periarticular injections
      from populations undergoing elective surgery to orthopaedic trauma patients with rotational
      ankle fractures.

      The study design is a prospective, double-blinded, randomized controlled trial. Patients
      included in the study will be randomly assigned to one of two treatment groups:
      intra-operative multimodal periarticular injection or control (no injection). The
      peri-incisional injection will consist of ropivacaine, epinephrine, and morphine. All
      pharmacologic agents in the anesthetic cocktail are FDA approved and have been previously
      used in combination during other types of orthopaedic surgeries.

      All patients included in the study will receive standard post-operative opioid analgesic
      regimens, administered 'per needed', regardless of their assigned treatment group per study
      protocol. ≥ 40 patients will be randomly assigned to each group. The patients enrolled in the
      investigation as well as health care professionals performing post-operative assessments and
      collecting data will be blinded to treatment allocation. The feasibility of multimodal
      peri-incisional injections is supported by their current efficacy in populations undergoing
      elective orthopedic surgeries. These injections may be equally effective at reducing pain
      compared to regional anesthesia with continuous infusions, and single-shot nerve blocks.

      The investigators hypothesize that the injection cohort will have reduced pain scores, lower
      narcotic requirements, shorter length of stay, and be more likely to discharge to home
      following surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Change in Post-operative Visual Analog Pain Scores
time frame: Immediately following surgery, then every 4 hours following surgery for 7 days. Patients will be re-evaluated every 3 months for up to 1 year post-operation
description: Patients will describe their current level of comfort on a 10 point scale while at rest. Zero corresponds to "no pain" and ten corresponds to "the most extreme possible pain." Visual analog scores will be collected by nursing staff who are blinded to the treatment allocation.
measure: Total post-operative narcotic consumption
time frame: From immediately following surgery to 90 days after.
description: Total post-operative opioid consumption expressed in morphine equivalent dose will be recorded, including IV and oral opioids.
measure: Post-operative length of stay
time frame: From immediately following surgery to 90 days after.
description: Number of days in the hospital following surgery
measure: Type of facility patient will go to after hospital discharge
time frame: From immediately following surgery to 90 days after.
description: e.g. Skilled Nursing Facility, Rehabilitation Center, Home. The location is always established prior to discharging a patient from the hospital. This information can be found on the patient's electronic medical record.
measure: Medication-related side effects
time frame: From immediately following surgery to 7 days after.
description: Patients will be monitored by nursing personnel for medication side effects related to ropivacaine toxicity including blurred vision, hearing problems, transient peripheral paralysis, dizziness, convulsion, uncontrolled muscle contraction, hypotension, bradycardia, and new onset arrhythmia.
arm group label: Peri-incisional injection
arm group type: Experimental
description: A single, 25 cc multimodal analgesic cocktail will be injected following completion of ankle fracture fixation/instrumentation while the patient remains under general anesthesia and prior to skin closure. The injection will be administered as such:
20 mL injected into the peri-incisional soft tissues in a circumferential fashion
5mL injected into the ankle joint This cocktail includes 200 mg of 0.8% ropivacaine, 0.6 mg of epinephrine, 5 mg of morphine sulfate, and sodium chloride solution. All infiltrations will be completed with a blunt trochar to minimize the risk of intravascular injection.
Interventions:
Drug: Ropivacaine Drug: Epinephrine Drug: Morphine Drug: 0.9% sodium chloride solution Following surgery, patients in the treatment and non-treatment groups will both be provided with the same intravenous (patient-controlled analgesia) and oral pain medications scheduled "per needed".
arm group label: Control
arm group type: No Intervention
description: Ankle fracture fixation/instrumentation will be completed per the standard of care. No peri-incisional injection will be completed.
intervention type: Drug
intervention name: Ropivacaine
arm group label: Peri-incisional injection
other name: Naropin
intervention type: Drug
intervention name: Epinephrine
arm group label: Peri-incisional injection
other name: Adrenalin
intervention type: Drug
intervention name: Morphine
arm group label: Peri-incisional injection
other name: Duramorph
intervention type: Drug
intervention name: 0.9% sodium chloride solution
arm group label: Peri-incisional injection
other name: 0.9% normal saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Kyle Hancock, MD
role: Principal Investigator
affiliation: Resident Physician
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Iowa
investigator full name: Kyle Hancock
investigator title: Resident Physician
mesh term: Pain, Postoperative
mesh term: Fractures, Bone
mesh term: Ankle Fractures
mesh term: Epinephrine
mesh term: Morphine
mesh term: Ropivacaine
sharing ipd: No
submitted: July 1, 2021
returned: July 22, 2021
submitted: June 28, 2022
returned: July 21, 2022