<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/NCT03812003</url>
  </required_header>
  <id_info>
    <org_study_id>2-107-05-162</org_study_id>
    <nct_id>NCT03812003</nct_id>
  </id_info>
  <brief_title>Investigation of the Strategy of Preventing Post-operative Opioid-induced Hyperalgesia</brief_title>
  <official_title>Investigation of the Strategy of Preventing Post-operative Opioid-induced Hyperalgesia by Remifentanil Infusion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tri-Service General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tri-Service General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The concept of Enhanced Recovery After Surgery(ERAS) has been prevalent in recent years. In&#xD;
      the ERAS guideline, short-acting anesthetics, instead of long-acting opioid anesthetics, were&#xD;
      recommended during surgery to decrease post-operative complication and length of hospital&#xD;
      stay. Propofol-remifentanil based total intravenous anesthesia (TIVA) can provide quicker&#xD;
      emergence and decreased post-operative nausea and vomiting. However, the prescription of&#xD;
      opioid (especially remifentanil) may induce opioid-induced hyperalgesia (OIH) and increase&#xD;
      the requirement of analgesics. Previous studies provided some strategies to prevent OIH. The&#xD;
      purpose of this study is to investigate the effect of adding remifentanil(1 mcg/kg) after&#xD;
      emergence and endotracheal extubation in breast cancer females receiving breast surgery under&#xD;
      propofol-remifentanil based TIVA for the prevention of OIH.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. After obtaining informed consent, patients will be randomized into two groups.&#xD;
&#xD;
        2. All patients receive remifentanil-propofol based TIVA and Bispectral index (BIS) monitor&#xD;
           during breast surgery. In the end of surgery, intravenous NSAID(keto) 30mg and local&#xD;
           anestehsia (Marcaine) infiltration around the surgical wound will be prescribed to&#xD;
           reduce post-operative pain.&#xD;
&#xD;
        3. group R(intervention): remifentanil 1mcg/kg diluted with 0.9% saline to 50ml and drip&#xD;
           for 30 minutes after emergence and extubation of endotracheal tube&#xD;
&#xD;
        4. group N(no intervention): 0.9% saline 50ml drip for 30 minutes after emergence and&#xD;
           extubation of endotracheal tube&#xD;
&#xD;
        5. In post-anesthesia room: record the numerical rating scale (NRS); requirement of&#xD;
           additional analgesics (rescue medication), blood pressure, heart rate, pulse oximeter,&#xD;
           degree of nausea, vomiting&#xD;
&#xD;
        6. In ward: record the numerical rating scale (NRS) and total analgesics consumption&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 11, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</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>
    <intervention_model_description>Breast cancer patient</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Numerical Rating Score (NRS) for pain score in post-anesthesia room (PAR)</measure>
    <time_frame>0 minutes</time_frame>
    <description>1.The pain after breast surgery is moderate and suppose to be reduced after combined prescription of NSAID and local analgesics. Post-operative pain is supposed to be related with hyperalgesia. 2.Record the degree of post-operative pain by Numerical Rating Scale (Numerical Rating Scale)(0-10; 0= no pain; 10=pain as bad as can be)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Numerical Rating Score (NRS) for pain score in post-anesthesia room (PAR)</measure>
    <time_frame>30 minutes</time_frame>
    <description>1.The pain after breast surgery is moderate and suppose to be reduced after combined prescription of NSAID and local analgesics. Post-operative pain is supposed to be related with hyperalgesia. 2.Record the degree of post-operative pain by Numerical Rating Scale (Numerical Rating Scale)(0-10; 0= no pain; 10=pain as bad as can be)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The amount analgesic requirement in post-anesthesia room (PAR)</measure>
    <time_frame>30 minutes</time_frame>
    <description>1.The pain after breast surgery is moderate and suppose to be reduced after combined prescription of NSAID and local analgesics during surgery. Post-operative pain is supposed to be related with hyperalgesia. 2.Record the degree of post-operative pain by record additional analgesics amount (rescue medication, mg) in PAR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>degree of post-operative nausea in post-anesthesia room (PAR)</measure>
    <time_frame>30 minutes</time_frame>
    <description>Record the degree of nausea in PAR: mild, moderate, severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>degree of post-operative vomiting in post-anesthesia room (PAR)</measure>
    <time_frame>30 minutes</time_frame>
    <description>Record the degree of vomiting in PAR: mild, moderate, severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>post-operative blood pressure in post-anesthesia room (PAR)</measure>
    <time_frame>0 minutes</time_frame>
    <description>Record the blood pressure(mmHg) in PAR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>post-operative systolic blood pressure in post-anesthesia room (PAR)</measure>
    <time_frame>0 minutes</time_frame>
    <description>Record the systolic blood pressure(mmHg) in PAR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>post-operative systolic blood pressure in post-anesthesia room (PAR)</measure>
    <time_frame>30 minutes</time_frame>
    <description>Record the systolic blood pressure(mmHg) in PAR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>post-operative diastolic blood pressure in post-anesthesia room (PAR)</measure>
    <time_frame>30 minutes</time_frame>
    <description>Record the diastolic blood pressure(mmHg) in PAR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>post-operative heart rate in post-anesthesia room (PAR)</measure>
    <time_frame>0 minutes</time_frame>
    <description>Record the heart rate (beat/min) in PAR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>post-operative heart rate in post-anesthesia room (PAR)</measure>
    <time_frame>30 minutes</time_frame>
    <description>Record the heart rate (beat/min) in PAR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>post-operative pulse oximeter in post-anesthesia room (PAR)</measure>
    <time_frame>0 minutes</time_frame>
    <description>Record the pulse oximeter(SpO2; %) in PAR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>postoperative pulse oximeter in post-anesthesia room (PAR)</measure>
    <time_frame>30 minutes</time_frame>
    <description>Record the pulse oximeter(SpO2; %) in PAR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numerical Rating Score (NRS) for pain score in ward</measure>
    <time_frame>1 hour after transferring to ward</time_frame>
    <description>Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numerical Rating Score (NRS) for pain score in ward</measure>
    <time_frame>2 hours after transferring to ward</time_frame>
    <description>Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numerical Rating Score (NRS) for pain score in ward</measure>
    <time_frame>4 hours after transferring to ward</time_frame>
    <description>Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numerical Rating Score (NRS) for pain score in ward</measure>
    <time_frame>8 hours after transferring to ward</time_frame>
    <description>Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numerical Rating Score (NRS) for pain score in ward</measure>
    <time_frame>24 hours after transferring to ward</time_frame>
    <description>Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>total analgesics requirement in ward</measure>
    <time_frame>24hr after transferring to ward</time_frame>
    <description>Record total analgesic requirement (mg) in ward</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Opioid-Induced Disorders</condition>
  <arm_group>
    <arm_group_label>remifentanil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After emergence and extubation of endotracheal tube, remifentanil 1mcg/kg were diluted with 0.9% saline to 50 ml, added in IV bag, and drip for 30 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>no intervention</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>After emergence and extubation of endotracheal tube, 0.9% saline 50ml were added in IV bag and drip for 30 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Remifentanil</intervention_name>
    <description>remifentanil 1mcg/kg added in 0.9% saline and diluted to 50ml</description>
    <arm_group_label>remifentanil</arm_group_label>
    <other_name>Remifentanil ALVOGEN powder</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject's ASA (American Society of Anesthesiologists) Physical Status Classification:&#xD;
             I (A normal healthy patient)~III(A patient with severe systemic disease)&#xD;
&#xD;
          -  Subject has breast cancer and scheduled for breast surgery using total-intravenous&#xD;
             anesthesia(TIVA)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject's ASA (American Society of Anesthesiologists) Physical Status Classification&#xD;
             &gt;3&#xD;
&#xD;
          -  Subject doesn't receive total-intravenous anesthesia(TIVA) during surgery&#xD;
&#xD;
          -  Subject has psychiatric disease&#xD;
&#xD;
          -  allergic to opioid or propofol&#xD;
&#xD;
          -  History of alcoholism&#xD;
&#xD;
          -  History of drug abuse&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>breast cancer female</gender_description>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jyh-cherng Yu, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Tri-Service General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wei-Hung Chan, MD</last_name>
    <phone>886-2-78923311</phone>
    <phone_ext>12546</phone_ext>
    <email>whcken@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zhi-Fu Wu, MD</last_name>
    <phone>886-2-78923311</phone>
    <phone_ext>12852</phone_ext>
    <email>aneswu@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Tri-Service General Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>114</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wei-Hung Chan, Doctorate</last_name>
      <phone>886-2-87923311</phone>
      <phone_ext>12546</phone_ext>
      <email>whcken@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Wei-Hung Chan, Doctorate</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 13, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>January 18, 2019</last_update_submitted>
  <last_update_submitted_qc>January 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tri-Service General Hospital</investigator_affiliation>
    <investigator_full_name>Wei-Hung Chan</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>opioid-induced hyperalgesia, remifentanil</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperalgesia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Remifentanil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Numerical rating scale, rescue analgesic amount</ipd_description>
  </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/NCT03812003
org study id: 2-107-05-162
nct id: NCT03812003
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The concept of Enhanced Recovery After Surgery(ERAS) has been prevalent in recent years. In
      the ERAS guideline, short-acting anesthetics, instead of long-acting opioid anesthetics, were
      recommended during surgery to decrease post-operative complication and length of hospital
      stay. Propofol-remifentanil based total intravenous anesthesia (TIVA) can provide quicker
      emergence and decreased post-operative nausea and vomiting. However, the prescription of
      opioid (especially remifentanil) may induce opioid-induced hyperalgesia (OIH) and increase
      the requirement of analgesics. Previous studies provided some strategies to prevent OIH. The
      purpose of this study is to investigate the effect of adding remifentanil(1 mcg/kg) after
      emergence and endotracheal extubation in breast cancer females receiving breast surgery under
      propofol-remifentanil based TIVA for the prevention of OIH.
1. After obtaining informed consent, patients will be randomized into two groups.

        2. All patients receive remifentanil-propofol based TIVA and Bispectral index (BIS) monitor
           during breast surgery. In the end of surgery, intravenous NSAID(keto) 30mg and local
           anestehsia (Marcaine) infiltration around the surgical wound will be prescribed to
           reduce post-operative pain.

        3. group R(intervention): remifentanil 1mcg/kg diluted with 0.9% saline to 50ml and drip
           for 30 minutes after emergence and extubation of endotracheal tube

        4. group N(no intervention): 0.9% saline 50ml drip for 30 minutes after emergence and
           extubation of endotracheal tube

        5. In post-anesthesia room: record the numerical rating scale (NRS); requirement of
           additional analgesics (rescue medication), blood pressure, heart rate, pulse oximeter,
           degree of nausea, vomiting

        6. In ward: record the numerical rating scale (NRS) and total analgesics consumption
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Breast cancer patient
primary purpose: Prevention
masking: Double (Participant, Care Provider)
measure: Numerical Rating Score (NRS) for pain score in post-anesthesia room (PAR)
time frame: 0 minutes
description: 1.The pain after breast surgery is moderate and suppose to be reduced after combined prescription of NSAID and local analgesics. Post-operative pain is supposed to be related with hyperalgesia. 2.Record the degree of post-operative pain by Numerical Rating Scale (Numerical Rating Scale)(0-10; 0= no pain; 10=pain as bad as can be)
measure: Numerical Rating Score (NRS) for pain score in post-anesthesia room (PAR)
time frame: 30 minutes
description: 1.The pain after breast surgery is moderate and suppose to be reduced after combined prescription of NSAID and local analgesics. Post-operative pain is supposed to be related with hyperalgesia. 2.Record the degree of post-operative pain by Numerical Rating Scale (Numerical Rating Scale)(0-10; 0= no pain; 10=pain as bad as can be)
measure: The amount analgesic requirement in post-anesthesia room (PAR)
time frame: 30 minutes
description: 1.The pain after breast surgery is moderate and suppose to be reduced after combined prescription of NSAID and local analgesics during surgery. Post-operative pain is supposed to be related with hyperalgesia. 2.Record the degree of post-operative pain by record additional analgesics amount (rescue medication, mg) in PAR
measure: degree of post-operative nausea in post-anesthesia room (PAR)
time frame: 30 minutes
description: Record the degree of nausea in PAR: mild, moderate, severe
measure: degree of post-operative vomiting in post-anesthesia room (PAR)
time frame: 30 minutes
description: Record the degree of vomiting in PAR: mild, moderate, severe
measure: post-operative blood pressure in post-anesthesia room (PAR)
time frame: 0 minutes
description: Record the blood pressure(mmHg) in PAR
measure: post-operative systolic blood pressure in post-anesthesia room (PAR)
time frame: 0 minutes
description: Record the systolic blood pressure(mmHg) in PAR
measure: post-operative systolic blood pressure in post-anesthesia room (PAR)
time frame: 30 minutes
description: Record the systolic blood pressure(mmHg) in PAR
measure: post-operative diastolic blood pressure in post-anesthesia room (PAR)
time frame: 30 minutes
description: Record the diastolic blood pressure(mmHg) in PAR
measure: post-operative heart rate in post-anesthesia room (PAR)
time frame: 0 minutes
description: Record the heart rate (beat/min) in PAR
measure: post-operative heart rate in post-anesthesia room (PAR)
time frame: 30 minutes
description: Record the heart rate (beat/min) in PAR
measure: post-operative pulse oximeter in post-anesthesia room (PAR)
time frame: 0 minutes
description: Record the pulse oximeter(SpO2; %) in PAR
measure: postoperative pulse oximeter in post-anesthesia room (PAR)
time frame: 30 minutes
description: Record the pulse oximeter(SpO2; %) in PAR
measure: Numerical Rating Score (NRS) for pain score in ward
time frame: 1 hour after transferring to ward
description: Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)
measure: Numerical Rating Score (NRS) for pain score in ward
time frame: 2 hours after transferring to ward
description: Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)
measure: Numerical Rating Score (NRS) for pain score in ward
time frame: 4 hours after transferring to ward
description: Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)
measure: Numerical Rating Score (NRS) for pain score in ward
time frame: 8 hours after transferring to ward
description: Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)
measure: Numerical Rating Score (NRS) for pain score in ward
time frame: 24 hours after transferring to ward
description: Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)
measure: total analgesics requirement in ward
time frame: 24hr after transferring to ward
description: Record total analgesic requirement (mg) in ward
arm group label: remifentanil
arm group type: Experimental
description: After emergence and extubation of endotracheal tube, remifentanil 1mcg/kg were diluted with 0.9% saline to 50 ml, added in IV bag, and drip for 30 minutes.
arm group label: no intervention
arm group type: No Intervention
description: After emergence and extubation of endotracheal tube, 0.9% saline 50ml were added in IV bag and drip for 30 minutes.
intervention type: Drug
intervention name: Remifentanil
description: remifentanil 1mcg/kg added in 0.9% saline and diluted to 50ml
arm group label: remifentanil
other name: Remifentanil ALVOGEN powder
criteria: 
gender: Female
gender based: Yes
gender description: breast cancer female
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: No
last name: Jyh-cherng Yu, MD
role: Study Chair
affiliation: Tri-Service General Hospital
last name: Wei-Hung Chan, MD
phone: 886-2-78923311
phone ext: 12546
email: whcken@gmail.com
last name: Zhi-Fu Wu, MD
phone: 886-2-78923311
phone ext: 12852
email: aneswu@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: Tri-Service General Hospital
investigator full name: Wei-Hung Chan
investigator title: Principal Investigator
mesh term: Hyperalgesia
mesh term: Remifentanil
sharing ipd: Undecided
ipd description: Numerical rating scale, rescue analgesic amount