<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/NCT03258697</url>
  </required_header>
  <id_info>
    <org_study_id>201602050A3</org_study_id>
    <nct_id>NCT03258697</nct_id>
  </id_info>
  <brief_title>The Pharmacokinetics and Effectiveness of Local LevoBupivacaine Injection on Primary Total Joint Replacement Model.</brief_title>
  <official_title>The Pharmacokinetics and Effectiveness of Different Methods of Local LevoBupivacaine Injection, a Prospective Randomized Case Control Clinical Study on Primary Total Joint Replacement Model.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chang Gung Memorial Hospital</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Total joint replacement is an ideal procedure to treat end stage joint disease. Good post-op&#xD;
      pain relief could accelerate patient recovery and rehabilitation, and decrease admission days&#xD;
      and medical cost. Local injection of LevoBupivacaine is an effective method in post-operative&#xD;
      pain control. The effectiveness of local analgesia was noticed clinically. However, thorough&#xD;
      studies about the pharmacokinetics of LevoBupivacaine, maintenance of effect, influence of&#xD;
      post-operative rehabilitation are not well studied in different way of injection. The purpose&#xD;
      of this study is to evaluate and analyze the pharmacokinetics and effect of local&#xD;
      Levobupivacaine injection in different ways, the amount of post-operative fentanyl&#xD;
      requirement after local injection, time to first fentanyl request, pain score, immediate&#xD;
      post-operative function, side effect of analgesic agents, and medical cost, and to improve&#xD;
      the quality of total joint replacement post-operative care.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Single large dose of LevoBupivacaine had been proved good analgesic effect in total joint&#xD;
      replacement surgery. However, the safety was not well studied. For better understanding the&#xD;
      effect and safety of local analgesic agent, we choose LevoBupivacaine with different&#xD;
      injection way to find out. We divide patient to three groups, for comparing the effectiveness&#xD;
      of LevoBupivacaine, and safety of LevoBupivacaine by checking intra-blood concentration. The&#xD;
      pre-emptive analgesics and post-operative analgesics were the same as routine protocol in&#xD;
      other total joint replacement.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">October 17, 2017</start_date>
  <completion_date type="Anticipated">February 28, 2020</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2019</primary_completion_date>
  <phase>N/A</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, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dosage of analgesic opioid agent</measure>
    <time_frame>post-operative day2</time_frame>
    <description>The total dosage of opioid agent after local LevoBupivacaine injection</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood concentration of LevoBupivacaine</measure>
    <time_frame>25min, 90min, and coming morning after LevoBupivacaine injection</time_frame>
    <description>Venous return of local LevoBupivacaine could cause the difference of blood concentration</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Functional score</measure>
    <time_frame>Baseline, Post-operative day1, day2, week2, week6, week12, week24</time_frame>
    <description>The difference of functional score</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">180</enrollment>
  <condition>Arthropathy</condition>
  <arm_group>
    <arm_group_label>Patient-Controlled Analgesia</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patient had no local analgesic agent during total joint replacement. Patient had baseline Patient-Controlled Analgesia pump.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Peri-articular LevoBupivacaine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient had periarticular local analgesic agent, LevoBupivacaine Hydrochloride, during total joint replacement. Patient had baseline Patient-Controlled Analgesia pump.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intra-articular LevoBupivacaine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient had intra-articular local analgesic agent, LevoBupivacaine Hydrochloride, during total joint replacement. Patient had baseline Patient-Controlled Analgesia pump.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levobupivacaine Hydrochloride</intervention_name>
    <description>Different way of LevoBupivacaine injection</description>
    <arm_group_label>Intra-articular LevoBupivacaine</arm_group_label>
    <arm_group_label>Peri-articular LevoBupivacaine</arm_group_label>
    <other_name>Chirocaine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Primary total joint replacement, no previous open surgery on the same joint&#xD;
&#xD;
          2. Age 50~80 y/o, Pre-operative diagnosis: degenerative osteoarthritis&#xD;
&#xD;
          3. Pre-operative deformity: varus &lt;15°, valgus &lt;15°, flexion contracture &lt;15°.&#xD;
&#xD;
          4. Patients with normal heart function&#xD;
&#xD;
          5. Willing to receive post-operative questionnaire and outpatient clinic follow-up&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Allergy to Patient-Controlled Analgesia or LevoBupivacaine&#xD;
&#xD;
          2. Mental or cognitive illness that couldn't well response to questionnaire&#xD;
&#xD;
          3. American Society Anesthesiologist more than III degree&#xD;
&#xD;
          4. Liver cirrhosis, chronic renal insufficiency, heart disease or arrhythmia,&#xD;
             insulin-dependent diabetes mellitus, and previous narcotic abuse history.&#xD;
&#xD;
          5. Not suitable for using patient-controlled analgesia pump by evaluation of&#xD;
             anesthesiologist&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wei-Chen Lo, M.S.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chang Gung Memorial Hospital, Linkou, Taiwan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital, Linkou</name>
      <address>
        <city>Taoyuan City</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <reference>
    <citation>Chen CC, Yang CC, Hu CC, Shih HN, Chang YH, Hsieh PH. Acupuncture for pain relief after total knee arthroplasty: a randomized controlled trial. Reg Anesth Pain Med. 2015 Jan-Feb;40(1):31-6. doi: 10.1097/AAP.0000000000000138.</citation>
    <PMID>25158837</PMID>
  </reference>
  <reference>
    <citation>Chen DW, Hu CC, Chang YH, Lee MS, Chang CJ, Hsieh PH. Intra-articular bupivacaine reduces postoperative pain and meperidine use after total hip arthroplasty: a randomized, double-blind study. J Arthroplasty. 2014 Dec;29(12):2457-61. doi: 10.1016/j.arth.2013.12.021. Epub 2013 Dec 19.</citation>
    <PMID>24439998</PMID>
  </reference>
  <reference>
    <citation>Parvataneni HK, Shah VP, Howard H, Cole N, Ranawat AS, Ranawat CS. Controlling pain after total hip and knee arthroplasty using a multimodal protocol with local periarticular injections: a prospective randomized study. J Arthroplasty. 2007 Sep;22(6 Suppl 2):33-8. doi: 10.1016/j.arth.2007.03.034. Epub 2007 Jul 26.</citation>
    <PMID>17823012</PMID>
  </reference>
  <reference>
    <citation>Wasudev G, Smith BE, Limbird TJ. Blood levels of bupivacaine after arthroscopy of the knee joint. Arthroscopy. 1990;6(1):40-2. doi: 10.1016/0749-8063(90)90095-u.</citation>
    <PMID>2310449</PMID>
  </reference>
  <reference>
    <citation>Meinig RP, Holtgrewe JL, Wiedel JD, Christie DB, Kestin KJ. Plasma bupivacaine levels following single dose intraarticular instillation for arthroscopy. Am J Sports Med. 1988 May-Jun;16(3):295-300. doi: 10.1177/036354658801600317.</citation>
    <PMID>3381989</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>January 29, 2018</last_update_submitted>
  <last_update_submitted_qc>January 29, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Local analgesia, Pharmacokinetics, Total joint replacement</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Joint Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Levobupivacaine</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/NCT03258697
org study id: 201602050A3
nct id: NCT03258697
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Total joint replacement is an ideal procedure to treat end stage joint disease. Good post-op
      pain relief could accelerate patient recovery and rehabilitation, and decrease admission days
      and medical cost. Local injection of LevoBupivacaine is an effective method in post-operative
      pain control. The effectiveness of local analgesia was noticed clinically. However, thorough
      studies about the pharmacokinetics of LevoBupivacaine, maintenance of effect, influence of
      post-operative rehabilitation are not well studied in different way of injection. The purpose
      of this study is to evaluate and analyze the pharmacokinetics and effect of local
      Levobupivacaine injection in different ways, the amount of post-operative fentanyl
      requirement after local injection, time to first fentanyl request, pain score, immediate
      post-operative function, side effect of analgesic agents, and medical cost, and to improve
      the quality of total joint replacement post-operative care.
Single large dose of LevoBupivacaine had been proved good analgesic effect in total joint
      replacement surgery. However, the safety was not well studied. For better understanding the
      effect and safety of local analgesic agent, we choose LevoBupivacaine with different
      injection way to find out. We divide patient to three groups, for comparing the effectiveness
      of LevoBupivacaine, and safety of LevoBupivacaine by checking intra-blood concentration. The
      pre-emptive analgesics and post-operative analgesics were the same as routine protocol in
      other total joint replacement.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Dosage of analgesic opioid agent
time frame: post-operative day2
description: The total dosage of opioid agent after local LevoBupivacaine injection
measure: Blood concentration of LevoBupivacaine
time frame: 25min, 90min, and coming morning after LevoBupivacaine injection
description: Venous return of local LevoBupivacaine could cause the difference of blood concentration
measure: Functional score
time frame: Baseline, Post-operative day1, day2, week2, week6, week12, week24
description: The difference of functional score
arm group label: Patient-Controlled Analgesia
arm group type: No Intervention
description: Patient had no local analgesic agent during total joint replacement. Patient had baseline Patient-Controlled Analgesia pump.
arm group label: Peri-articular LevoBupivacaine
arm group type: Active Comparator
description: Patient had periarticular local analgesic agent, LevoBupivacaine Hydrochloride, during total joint replacement. Patient had baseline Patient-Controlled Analgesia pump.
arm group label: Intra-articular LevoBupivacaine
arm group type: Experimental
description: Patient had intra-articular local analgesic agent, LevoBupivacaine Hydrochloride, during total joint replacement. Patient had baseline Patient-Controlled Analgesia pump.
intervention type: Drug
intervention name: Levobupivacaine Hydrochloride
description: Different way of LevoBupivacaine injection
arm group label: Intra-articular LevoBupivacaine
arm group label: Peri-articular LevoBupivacaine
other name: Chirocaine
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: No
last name: Wei-Chen Lo, M.S.
role: Principal Investigator
affiliation: Chang Gung Memorial Hospital, Linkou, Taiwan
facility: 
country: Taiwan
citation: Chen CC, Yang CC, Hu CC, Shih HN, Chang YH, Hsieh PH. Acupuncture for pain relief after total knee arthroplasty: a randomized controlled trial. Reg Anesth Pain Med. 2015 Jan-Feb;40(1):31-6. doi: 10.1097/AAP.0000000000000138.
PMID: 25158837
citation: Chen DW, Hu CC, Chang YH, Lee MS, Chang CJ, Hsieh PH. Intra-articular bupivacaine reduces postoperative pain and meperidine use after total hip arthroplasty: a randomized, double-blind study. J Arthroplasty. 2014 Dec;29(12):2457-61. doi: 10.1016/j.arth.2013.12.021. Epub 2013 Dec 19.
PMID: 24439998
citation: Parvataneni HK, Shah VP, Howard H, Cole N, Ranawat AS, Ranawat CS. Controlling pain after total hip and knee arthroplasty using a multimodal protocol with local periarticular injections: a prospective randomized study. J Arthroplasty. 2007 Sep;22(6 Suppl 2):33-8. doi: 10.1016/j.arth.2007.03.034. Epub 2007 Jul 26.
PMID: 17823012
citation: Wasudev G, Smith BE, Limbird TJ. Blood levels of bupivacaine after arthroscopy of the knee joint. Arthroscopy. 1990;6(1):40-2. doi: 10.1016/0749-8063(90)90095-u.
PMID: 2310449
citation: Meinig RP, Holtgrewe JL, Wiedel JD, Christie DB, Kestin KJ. Plasma bupivacaine levels following single dose intraarticular instillation for arthroscopy. Am J Sports Med. 1988 May-Jun;16(3):295-300. doi: 10.1177/036354658801600317.
PMID: 3381989
responsible party type: Sponsor
mesh term: Joint Diseases
mesh term: Levobupivacaine