<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/NCT03296488</url>
  </required_header>
  <id_info>
    <org_study_id>KMUHIRB-F(I)-20170089</org_study_id>
    <nct_id>NCT03296488</nct_id>
  </id_info>
  <brief_title>The Efficacy and Safety of NALDEBAIN for the Treatment of Post-Laparotomy Surgery</brief_title>
  <official_title>A Randomized Controlled Trial to Compare the Efficacy and Safety of NALDEBAIN With Intravenous Patient-Controlled Analgesia With Fentanyl for the Treatment of Post-Laparotomy Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kaohsiung Medical University Chung-Ho Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kaohsiung Medical University Chung-Ho Memorial 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to determine the safety and efficacy of single doses&#xD;
      of intramuscular NALDEBAIN on patients scheduled to undergo elective laparotomy. This will be&#xD;
      performed by administering NALDEBAIN pre-operatively to subjects scheduled to undergo&#xD;
      elective laparotomy, and assessing the safety and efficacy of the drug compared to PCA with&#xD;
      fentanyl. The study will demonstrate whether single use of NALDEBAIN is noninferior to PCA&#xD;
      with fentanyl or not.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Screening (Days -30 to -1) (All Study Subjects)&#xD;
&#xD;
      The nature of the study, as well as the potential risks and benefits associated with study&#xD;
      participation, will be fully explained to all potential subjects. The following will then be&#xD;
      obtained:&#xD;
&#xD;
        -  Informed consent.&#xD;
&#xD;
        -  Demographic information, including sex, age, BMI and type of surgery.&#xD;
&#xD;
        -  Vital signs, including temperature, respiratory rate, blood pressure and heart rate.&#xD;
&#xD;
        -  Medical history, including medication use and history of allergy.&#xD;
&#xD;
        -  Physical examination.&#xD;
&#xD;
        -  Laboratory testing, including hematological and biochemical tests, and urinalysis.&#xD;
&#xD;
        -  ECG and X-ray.&#xD;
&#xD;
      Study Day -1 (All Eligible Subjects)&#xD;
&#xD;
        -  Eligible subjects will be required to check into the clinical site before surgery (Day&#xD;
           -1). The following procedures will be performed upon check-in:&#xD;
&#xD;
             -  Review inclusion/exclusion criteria&#xD;
&#xD;
             -  Randomization&#xD;
&#xD;
             -  Review of concomitant medications&#xD;
&#xD;
             -  Review of adverse events&#xD;
&#xD;
        -  Additional laboratory tests will be requested as needed deciding by the investigator.&#xD;
&#xD;
        -  All eligible subjects will hospitalize and be randomized into one of two treatment&#xD;
           groups:&#xD;
&#xD;
             -  Group 1 - Intramuscular NALDEBAIN.&#xD;
&#xD;
             -  Group 2 - Intravenous PCA with fentanyl. Group 1 will receive single dose of&#xD;
                NALDEBAIN (150 mg Nalbuphine Sebacate) intramuscularly 24±12 hours before surgery.&#xD;
&#xD;
      Group 2 will receive intravenous patient-controlled analgesia with fentanyl through 48 hours&#xD;
      after surgery.&#xD;
&#xD;
        -  Pain assessment: group 1 and 2 will rate their pain intensity using a VAS pain scale&#xD;
           prior dosing or at Day -1 respectively.&#xD;
&#xD;
        -  Brief Pain Inventory (BPI) will be evaluated at Day -1.&#xD;
&#xD;
        -  Vital signs will be checked prior to dosing and once daily before Day 6.&#xD;
&#xD;
        -  Group 1 received NALDEBAIN will evaluate injection site within 1 hour prior to dosing.&#xD;
&#xD;
      Study Day 0-5 All subjects will be given general anesthesia prior to their scheduled surgical&#xD;
      procedure.&#xD;
&#xD;
      If patients need additional medication for treatment of pain, Ketorolac and Morphine could be&#xD;
      used as supplemental analgesics when they needed.&#xD;
&#xD;
      After surgery, the following evaluations will be performed:&#xD;
&#xD;
        -  Pain assessment: All subjects will rate their average pain intensity using a VAS pain&#xD;
           scale. The assessment will perform before the first use of PCA or supplemental&#xD;
           analgesics and at 4±1, 24±2, 32±3, 48±4 hours and once daily on Days 3 to Day 5 after&#xD;
           the surgery.&#xD;
&#xD;
        -  Brief Pain Inventory (BPI) will be evaluated at Day 2.&#xD;
&#xD;
        -  Vital signs (temperature, respiratory rate, blood pressure and heart rate) will be&#xD;
           checked once daily before Day 6.&#xD;
&#xD;
        -  In Group 1 (NALDEBAIN group), the injection site will be evaluated once daily before&#xD;
           final visit.&#xD;
&#xD;
        -  Review of concomitant medication and adverse event record.&#xD;
&#xD;
        -  In Group 2 (PCA group), the amount of fentanyl used will be recorded on Days 0 through&#xD;
           2.&#xD;
&#xD;
      Study Day 6 Evaluate the following items at Day 6.&#xD;
&#xD;
        -  Pain assessment: Subjects will rate their pain intensity in the patient diary.&#xD;
&#xD;
        -  Brief Pain Inventory (BPI) will be evaluated.&#xD;
&#xD;
        -  Vital signs (temperature, respiratory rate, blood pressure and heart rate) will be&#xD;
           checked.&#xD;
&#xD;
        -  Injection site evaluation.&#xD;
&#xD;
        -  Review of the adverse event record.&#xD;
&#xD;
        -  Review of concomitant medication. Final Visit (Day of Discharge, Day 6~30)&#xD;
&#xD;
        -  Vital signs (temperature, respiratory rate, blood pressure and heart rate) will be&#xD;
           checked&#xD;
&#xD;
        -  Injection site evaluation&#xD;
&#xD;
        -  Laboratory tests, including hematological and biochemical tests, and urinalysis.&#xD;
&#xD;
        -  Patient satisfaction: At the final visit, each subject was asked the following question:&#xD;
           &quot;How satisfied were you with your postsurgical analgesia&quot;? Subjects were asked to&#xD;
           classify themselves as either &quot;highly satisfied&quot;, &quot;satisfied&quot;, &quot;uncertain&quot;,&#xD;
           &quot;dissatisfied&quot;, or &quot;very dissatisfied&quot;.&#xD;
&#xD;
        -  Physical examination.&#xD;
&#xD;
        -  Review of the adverse event record.&#xD;
&#xD;
        -  Review of concomitant medication.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 17, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2018</completion_date>
  <primary_completion_date type="Anticipated">December 31, 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>pain assessment (post-OP 48 hours)</measure>
    <time_frame>During post-OP 48 hours</time_frame>
    <description>Pain assessment (time-specific pain intensity) calculated as the area under the curve of VAS pain intensity scores through 48 hours after surgery.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>supplemental analgesics</measure>
    <time_frame>From post-OP to Day 6</time_frame>
    <description>The consumption of total amount (mg) of supplemental analgesics administered after surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain assessment (post-OP to Day 6)</measure>
    <time_frame>From post-OP to Day 6</time_frame>
    <description>Pain assessment calculated as the area under the curve of VAS pain intensity scores through end of surgery to Day 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brief Pain Inventory</measure>
    <time_frame>pre-OP Day -1, post-OP Day 2 and Day 6</time_frame>
    <description>Pain intensity and interference of Brief Pain Inventory (BPI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>On discharge Day, between post-OP Day 7 and Day 14</time_frame>
    <description>Patient satisfaction on a 5-point rating.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of postoperative hospital stay</measure>
    <time_frame>From post-OP to Discharge Day, about 1 to 2 weeks</time_frame>
    <description>Length of postoperative hospital stay.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Adverse event</measure>
    <time_frame>From post-OP Day 1 to Discharge Day, about 1 to 2 weeks</time_frame>
    <description>Incidence of treatment-emergent adverse event (TEAE)</description>
  </other_outcome>
  <other_outcome>
    <measure>other abnormalities</measure>
    <time_frame>From Screening Day to Discharge Day, about 1 to 2 weeks</time_frame>
    <description>Percentage of abnormal from baseline to final visit in vital signs, laboratory tests and injection site evaluations.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">110</enrollment>
  <condition>Pain, Postoperative</condition>
  <arm_group>
    <arm_group_label>Nalbuphine Sebacate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>receive single dose of NALDEBAIN (150 mg Nalbuphine Sebacate, 75 mg/ml, 2 ml/vial) intramuscularly 24±12 hours before surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fentanyl Citrate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>receive intravenous patient-controlled analgesia with fentanyl through 48 hours after surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nalbuphine Sebacate</intervention_name>
    <description>intramuscular single dose of NALDEBAIN 24±12 hours before surgery.</description>
    <arm_group_label>Nalbuphine Sebacate</arm_group_label>
    <other_name>NALDEBAIN</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl Citrate</intervention_name>
    <description>Intravenous patient-controlled analgesia with fentanyl through 48 hours after surgery.</description>
    <arm_group_label>Fentanyl Citrate</arm_group_label>
    <other_name>PCA with fentanyl</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female who is among 20 to 80 years of age at screening.&#xD;
&#xD;
          -  Scheduled to electively undergo open-laparotomy.&#xD;
&#xD;
          -  American Society of Anesthesiology Physical Class 1-3.&#xD;
&#xD;
          -  Ability and willingness to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Body mass index less than 18 kg/m2 or greater than 30 kg/m2.&#xD;
&#xD;
          -  History of previous open-laparotomy.&#xD;
&#xD;
          -  Surgery with major complication, or need blood transfusion.&#xD;
&#xD;
          -  History of hypersensitivity or adverse reaction to local anesthetics, opioid, or any&#xD;
             ingredient of the medications administered in this study.&#xD;
&#xD;
          -  Severe comorbidity.&#xD;
&#xD;
          -  Chronic preoperative opioid consumption.&#xD;
&#xD;
          -  Pregnant or breastfeeding.&#xD;
&#xD;
          -  Inability to use the PCA device.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jaw-Yuan Wang, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chung-Ho Memorial Hospital, Kaohsiung Medical University:</name>
      <address>
        <city>Kaohsiung</city>
        <zip>807</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jaw-Yuan Wang, PhD</last_name>
      <phone>+886-7-3121101</phone>
      <phone_ext>5575</phone_ext>
      <email>cy614112@ms14.hinet.net</email>
    </contact>
    <contact_backup>
      <last_name>Tsung-Kun Chang, MD</last_name>
      <phone>+886-7-3121101</phone>
      <phone_ext>5575</phone_ext>
      <email>tsungkunchang@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Jaw-Yuan Wang, Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tsung-Kun Chang, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>September 23, 2017</last_update_submitted>
  <last_update_submitted_qc>September 23, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Kaohsiung Medical University Chung-Ho Memorial Hospital</investigator_affiliation>
    <investigator_full_name>Jaw-Yuan Wang, MD, PhD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>post-laparotomy wound pain</keyword>
  <keyword>NALDEBAIN (150 mg Nalbuphine Sebacate)</keyword>
  <keyword>PCA (patient-control-ed alagesia)</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>Fentanyl</mesh_term>
    <mesh_term>Nalbuphine</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/NCT03296488
org study id: KMUHIRB-F(I)-20170089
nct id: NCT03296488
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to determine the safety and efficacy of single doses
      of intramuscular NALDEBAIN on patients scheduled to undergo elective laparotomy. This will be
      performed by administering NALDEBAIN pre-operatively to subjects scheduled to undergo
      elective laparotomy, and assessing the safety and efficacy of the drug compared to PCA with
      fentanyl. The study will demonstrate whether single use of NALDEBAIN is noninferior to PCA
      with fentanyl or not.
Screening (Days -30 to -1) (All Study Subjects)

      The nature of the study, as well as the potential risks and benefits associated with study
      participation, will be fully explained to all potential subjects. The following will then be
      obtained:

        -  Informed consent.

        -  Demographic information, including sex, age, BMI and type of surgery.

        -  Vital signs, including temperature, respiratory rate, blood pressure and heart rate.

        -  Medical history, including medication use and history of allergy.

        -  Physical examination.

        -  Laboratory testing, including hematological and biochemical tests, and urinalysis.

        -  ECG and X-ray.

      Study Day -1 (All Eligible Subjects)

        -  Eligible subjects will be required to check into the clinical site before surgery (Day
           -1). The following procedures will be performed upon check-in:

             -  Review inclusion/exclusion criteria

             -  Randomization

             -  Review of concomitant medications

             -  Review of adverse events

        -  Additional laboratory tests will be requested as needed deciding by the investigator.

        -  All eligible subjects will hospitalize and be randomized into one of two treatment
           groups:

             -  Group 1 - Intramuscular NALDEBAIN.

             -  Group 2 - Intravenous PCA with fentanyl. Group 1 will receive single dose of
                NALDEBAIN (150 mg Nalbuphine Sebacate) intramuscularly 24±12 hours before surgery.

      Group 2 will receive intravenous patient-controlled analgesia with fentanyl through 48 hours
      after surgery.

        -  Pain assessment: group 1 and 2 will rate their pain intensity using a VAS pain scale
           prior dosing or at Day -1 respectively.

        -  Brief Pain Inventory (BPI) will be evaluated at Day -1.

        -  Vital signs will be checked prior to dosing and once daily before Day 6.

        -  Group 1 received NALDEBAIN will evaluate injection site within 1 hour prior to dosing.

      Study Day 0-5 All subjects will be given general anesthesia prior to their scheduled surgical
      procedure.

      If patients need additional medication for treatment of pain, Ketorolac and Morphine could be
      used as supplemental analgesics when they needed.

      After surgery, the following evaluations will be performed:

        -  Pain assessment: All subjects will rate their average pain intensity using a VAS pain
           scale. The assessment will perform before the first use of PCA or supplemental
           analgesics and at 4±1, 24±2, 32±3, 48±4 hours and once daily on Days 3 to Day 5 after
           the surgery.

        -  Brief Pain Inventory (BPI) will be evaluated at Day 2.

        -  Vital signs (temperature, respiratory rate, blood pressure and heart rate) will be
           checked once daily before Day 6.

        -  In Group 1 (NALDEBAIN group), the injection site will be evaluated once daily before
           final visit.

        -  Review of concomitant medication and adverse event record.

        -  In Group 2 (PCA group), the amount of fentanyl used will be recorded on Days 0 through
           2.

      Study Day 6 Evaluate the following items at Day 6.

        -  Pain assessment: Subjects will rate their pain intensity in the patient diary.

        -  Brief Pain Inventory (BPI) will be evaluated.

        -  Vital signs (temperature, respiratory rate, blood pressure and heart rate) will be
           checked.

        -  Injection site evaluation.

        -  Review of the adverse event record.

        -  Review of concomitant medication. Final Visit (Day of Discharge, Day 6~30)

        -  Vital signs (temperature, respiratory rate, blood pressure and heart rate) will be
           checked

        -  Injection site evaluation

        -  Laboratory tests, including hematological and biochemical tests, and urinalysis.

        -  Patient satisfaction: At the final visit, each subject was asked the following question:
           "How satisfied were you with your postsurgical analgesia"? Subjects were asked to
           classify themselves as either "highly satisfied", "satisfied", "uncertain",
           "dissatisfied", or "very dissatisfied".

        -  Physical examination.

        -  Review of the adverse event record.

        -  Review of concomitant medication.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: pain assessment (post-OP 48 hours)
time frame: During post-OP 48 hours
description: Pain assessment (time-specific pain intensity) calculated as the area under the curve of VAS pain intensity scores through 48 hours after surgery.
measure: supplemental analgesics
time frame: From post-OP to Day 6
description: The consumption of total amount (mg) of supplemental analgesics administered after surgery.
measure: Pain assessment (post-OP to Day 6)
time frame: From post-OP to Day 6
description: Pain assessment calculated as the area under the curve of VAS pain intensity scores through end of surgery to Day 6
measure: Brief Pain Inventory
time frame: pre-OP Day -1, post-OP Day 2 and Day 6
description: Pain intensity and interference of Brief Pain Inventory (BPI)
measure: Patient satisfaction
time frame: On discharge Day, between post-OP Day 7 and Day 14
description: Patient satisfaction on a 5-point rating.
measure: Length of postoperative hospital stay
time frame: From post-OP to Discharge Day, about 1 to 2 weeks
description: Length of postoperative hospital stay.
measure: Adverse event
time frame: From post-OP Day 1 to Discharge Day, about 1 to 2 weeks
description: Incidence of treatment-emergent adverse event (TEAE)
measure: other abnormalities
time frame: From Screening Day to Discharge Day, about 1 to 2 weeks
description: Percentage of abnormal from baseline to final visit in vital signs, laboratory tests and injection site evaluations.
arm group label: Nalbuphine Sebacate
arm group type: Experimental
description: receive single dose of NALDEBAIN (150 mg Nalbuphine Sebacate, 75 mg/ml, 2 ml/vial) intramuscularly 24±12 hours before surgery.
arm group label: Fentanyl Citrate
arm group type: Active Comparator
description: receive intravenous patient-controlled analgesia with fentanyl through 48 hours after surgery.
intervention type: Drug
intervention name: Nalbuphine Sebacate
description: intramuscular single dose of NALDEBAIN 24±12 hours before surgery.
arm group label: Nalbuphine Sebacate
other name: NALDEBAIN
intervention type: Drug
intervention name: Fentanyl Citrate
description: Intravenous patient-controlled analgesia with fentanyl through 48 hours after surgery.
arm group label: Fentanyl Citrate
other name: PCA with fentanyl
criteria: 
gender: All
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: No
last name: Jaw-Yuan Wang, PhD
role: Study Chair
affiliation: Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: Kaohsiung Medical University Chung-Ho Memorial Hospital
investigator full name: Jaw-Yuan Wang, MD, PhD
investigator title: Professor
mesh term: Pain, Postoperative
mesh term: Fentanyl
mesh term: Nalbuphine
sharing ipd: No