<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/NCT03256487</url>
  </required_header>
  <id_info>
    <org_study_id>IRB17-04172B</org_study_id>
    <nct_id>NCT03256487</nct_id>
  </id_info>
  <brief_title>Intravenous Buprenorphine Versus Morphine for Severe Pain in the Emergency Department</brief_title>
  <official_title>Intravenous Buprenorphine Versus Morphine for Severe Pain in the Emergency Department</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alameda Health System</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alameda Health System</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>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates intravenous (IV) buprenorphine versus IV morphine for the management of&#xD;
      severe, acute pain among emergency department (ED) patients. ED patients with severe pain&#xD;
      will be randomized in equal proportion to receive IV buprenorphine or IV morphine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Buprenorphine is classified as a partial mu opioid agonist and a weak kappa antagonist. In&#xD;
      lower doses, buprenorphine has an analgesic potency 25 to 40 times more potent than similar&#xD;
      milligram dosages of morphine. Consistent with its partial agonist activity, an apparent&#xD;
      ceiling effect for opioid-induced ventilatory impairment has been demonstrated. These&#xD;
      properties would suggest that buprenorphine is an effective analgesic with a favorable safety&#xD;
      profile.&#xD;
&#xD;
      Objective: The objective of this study is to determine if there is a clinically significant&#xD;
      difference in reduction of pain scores, measured by the Numeric Rating Scale (NRS), between&#xD;
      intravenous (IV) buprenorphine and IV morphine for severe pain in patients presenting to the&#xD;
      Alameda Health System--Highland Hospital ED. The investigators are evaluating if IV&#xD;
      buprenorphine is non-inferior to IV morphing. The investigators hypothesize that&#xD;
      buprenorphine will provide equivalent analgesic effects as morphine at 60 minutes, with a&#xD;
      lower proportion of medication adverse effects.&#xD;
&#xD;
      Study Design: This is a double-blinded, randomized controlled non-inferiority trial comparing&#xD;
      the analgesic efficacy of intravenous buprenorphine versus intravenous morphine for ED&#xD;
      patients presenting with severe, acute pain.&#xD;
&#xD;
      Participants: ED patients aged ≥18 years old who present with severe (pain NRS ≥7), acute&#xD;
      pain warranting (according the treating provider's judgment) and able to receive IV opioid&#xD;
      analgesia. The investigators will exclude pregnant patients, patients deemed too critically&#xD;
      ill by the provider, patients with allergy to buprenorphine or morphine, patients in custody,&#xD;
      patients on methadone, patients who have taken/received short acting opioid medications in&#xD;
      the last 12 hours, and patients who have taken/received long acting opioid medication in the&#xD;
      past 24 hours.&#xD;
&#xD;
      Intervention: In arm A, patients will receive IV Buprenorphine 0.3mg diluted to a volume of&#xD;
      10mL with NS in a plastic syringe administered over 3-5 minute. In arm B, patients will&#xD;
      receive IV morphine 0.1mg/kg (max 10mg) over 3-5 minutes. In both arms, at 20 minutes the&#xD;
      patient will be asked &quot;would you like more pain medication?&quot; If he/she answers &quot;yes&quot;, then&#xD;
      he/she will receive a second dose of the same amount of medication they previously received&#xD;
      based on the randomized arm they were placed into. At the end of the study time, 60 minutes,&#xD;
      the patient's ongoing pain management will be left to the attending physician caring for the&#xD;
      patient in the ED.&#xD;
&#xD;
      Data Collection: For both arms, the patients' NRS pain scores and adverse effects will be&#xD;
      queried at times 0, 10min, 20 min, 30min, 40min, 50 min, and 60 min. Demographic and&#xD;
      comorbidity data points will be abstracted during or after the study's conclusion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 26, 2017</start_date>
  <completion_date type="Anticipated">July 1, 2018</completion_date>
  <primary_completion_date type="Anticipated">February 1, 2018</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The provider, nurse administering the medication, patient, and research assistant will be masked to the randomization and the drug provided. We will ensure masking by the following mechanisms: drugs will be prepared by the pharmacy staff in identical 10mL syringes; the medication will be diluted to a volume of 10mL with normal saline (NS); and both medications are clear so the syringes will appear identical. Both drugs will be administered over the same period of time, 3-5 minutes.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Pain score difference at 60 minutes</measure>
    <time_frame>60 minutes</time_frame>
    <description>The difference in pain scores (measured by NRS) between the two arms at 60 minutes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain score difference at 50 minutes</measure>
    <time_frame>50 minutes</time_frame>
    <description>The difference in pain scores (measured by NRS) between the two arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain score difference at 40 minutes</measure>
    <time_frame>40 minutes</time_frame>
    <description>The difference in pain scores (measured by NRS) between the two arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain score difference at 30 minutes</measure>
    <time_frame>30 minutes</time_frame>
    <description>The difference in pain scores (measured by NRS) between the two arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain score difference at 20 minutes</measure>
    <time_frame>20 minutes</time_frame>
    <description>The difference in pain scores (measured by NRS) between the two arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain score difference at 10 minutes</measure>
    <time_frame>10 minutes</time_frame>
    <description>The difference in pain scores (measured by NRS) between the two arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>10, 20, 30, 40, 50, and 60 minutes</time_frame>
    <description>Hypertension (SBP &gt; 180) from documented vital signs,hypotension (SBP &lt;90) from documented vital signs, hypoxia (oxygen saturation &lt; 90%), respiratory depression (RR&lt;8 or need for mechanical intervention), nausea, vomiting, symptoms of opiate withdrawal (diarrhea, abdominal pain, diaphoresis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain reduction</measure>
    <time_frame>10, 20, 30, 40, 50, and 60 minutes</time_frame>
    <description>Pain reduction at each time point. Measured by NRS (time 0) minus NRS (time x)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Successful analgesia</measure>
    <time_frame>60 minutes</time_frame>
    <description>Proportion of patients with NRS &lt; 3 at 60 minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Repeat dosing</measure>
    <time_frame>20 minutes</time_frame>
    <description>Proportion of patients requiring reducing of analgesia at 20 minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summed Pain Intensity difference</measure>
    <time_frame>60 minutes</time_frame>
    <description>Measurement combining relief magnitude and duration in a single score</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">122</enrollment>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Buprenorphine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive IV buprenorphine 0.3mg diluted to a volume of 10mL with NS in a plastic syringe administered over 3-5 minutes. At 20 minutes, the patient will be asked &quot;would you like more pain medication?&quot; If he/she answers &quot;yes&quot;, then he/she will receive a second dose of IV buprenorphine 0.3mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Morphine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive IV morphine 0.1mg/kg (max dose 8mg) diluted to a volume of 10mL with NS in a plastic syringe administered over 3-5 minutes. At 20 minutes, the patient will be asked &quot;would you like more pain medication?&quot; If he/she answers &quot;yes&quot;, then he/she will receive a second dose of IV morphine 0.1mg/kg (max dose 8mg).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Buprenorphine</intervention_name>
    <description>buprenorphine 0.3mg IV</description>
    <arm_group_label>Buprenorphine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine Sulfate</intervention_name>
    <description>morphine 0.1 mg/kg IV (max 8mg per dose)</description>
    <arm_group_label>Morphine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ED patients with acute pain NRS ≥7 warranting IV opioid analgesia (according to ED&#xD;
             provider)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient refusal&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
               -  level 1 trauma patients&#xD;
&#xD;
               -  patients deemed critically ill by provider&#xD;
&#xD;
               -  patients in custody&#xD;
&#xD;
               -  patients on methadone&#xD;
&#xD;
               -  Patients who have received or taken any short acting opioid medication in the&#xD;
                  past 12 hours.&#xD;
&#xD;
               -  Patients who have received or taken any long acting opioid medication in the past&#xD;
                  24 hours.&#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_contact>
    <last_name>David Duong, MD MS</last_name>
    <phone>510-437-4573</phone>
    <email>dduong@alamedahealthsystem.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Alameda Health System, Highland Hospital</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94602</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David K Duong, MD MS</last_name>
      <phone>617-412-5111</phone>
      <email>dduong@alamedahealthsystem.org</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>August 18, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>October 17, 2017</last_update_submitted>
  <last_update_submitted_qc>October 17, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Alameda Health System</investigator_affiliation>
    <investigator_full_name>David Duong</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Emergencies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Buprenorphine</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/NCT03256487
org study id: IRB17-04172B
nct id: NCT03256487
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study evaluates intravenous (IV) buprenorphine versus IV morphine for the management of
      severe, acute pain among emergency department (ED) patients. ED patients with severe pain
      will be randomized in equal proportion to receive IV buprenorphine or IV morphine.
Buprenorphine is classified as a partial mu opioid agonist and a weak kappa antagonist. In
      lower doses, buprenorphine has an analgesic potency 25 to 40 times more potent than similar
      milligram dosages of morphine. Consistent with its partial agonist activity, an apparent
      ceiling effect for opioid-induced ventilatory impairment has been demonstrated. These
      properties would suggest that buprenorphine is an effective analgesic with a favorable safety
      profile.

      Objective: The objective of this study is to determine if there is a clinically significant
      difference in reduction of pain scores, measured by the Numeric Rating Scale (NRS), between
      intravenous (IV) buprenorphine and IV morphine for severe pain in patients presenting to the
      Alameda Health System--Highland Hospital ED. The investigators are evaluating if IV
      buprenorphine is non-inferior to IV morphing. The investigators hypothesize that
      buprenorphine will provide equivalent analgesic effects as morphine at 60 minutes, with a
      lower proportion of medication adverse effects.

      Study Design: This is a double-blinded, randomized controlled non-inferiority trial comparing
      the analgesic efficacy of intravenous buprenorphine versus intravenous morphine for ED
      patients presenting with severe, acute pain.

      Participants: ED patients aged ≥18 years old who present with severe (pain NRS ≥7), acute
      pain warranting (according the treating provider's judgment) and able to receive IV opioid
      analgesia. The investigators will exclude pregnant patients, patients deemed too critically
      ill by the provider, patients with allergy to buprenorphine or morphine, patients in custody,
      patients on methadone, patients who have taken/received short acting opioid medications in
      the last 12 hours, and patients who have taken/received long acting opioid medication in the
      past 24 hours.

      Intervention: In arm A, patients will receive IV Buprenorphine 0.3mg diluted to a volume of
      10mL with NS in a plastic syringe administered over 3-5 minute. In arm B, patients will
      receive IV morphine 0.1mg/kg (max 10mg) over 3-5 minutes. In both arms, at 20 minutes the
      patient will be asked "would you like more pain medication?" If he/she answers "yes", then
      he/she will receive a second dose of the same amount of medication they previously received
      based on the randomized arm they were placed into. At the end of the study time, 60 minutes,
      the patient's ongoing pain management will be left to the attending physician caring for the
      patient in the ED.

      Data Collection: For both arms, the patients' NRS pain scores and adverse effects will be
      queried at times 0, 10min, 20 min, 30min, 40min, 50 min, and 60 min. Demographic and
      comorbidity data points will be abstracted during or after the study's conclusion.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The provider, nurse administering the medication, patient, and research assistant will be masked to the randomization and the drug provided. We will ensure masking by the following mechanisms: drugs will be prepared by the pharmacy staff in identical 10mL syringes; the medication will be diluted to a volume of 10mL with normal saline (NS); and both medications are clear so the syringes will appear identical. Both drugs will be administered over the same period of time, 3-5 minutes.
measure: Pain score difference at 60 minutes
time frame: 60 minutes
description: The difference in pain scores (measured by NRS) between the two arms at 60 minutes.
measure: Pain score difference at 50 minutes
time frame: 50 minutes
description: The difference in pain scores (measured by NRS) between the two arms.
measure: Pain score difference at 40 minutes
time frame: 40 minutes
description: The difference in pain scores (measured by NRS) between the two arms.
measure: Pain score difference at 30 minutes
time frame: 30 minutes
description: The difference in pain scores (measured by NRS) between the two arms.
measure: Pain score difference at 20 minutes
time frame: 20 minutes
description: The difference in pain scores (measured by NRS) between the two arms.
measure: Pain score difference at 10 minutes
time frame: 10 minutes
description: The difference in pain scores (measured by NRS) between the two arms.
measure: Adverse events
time frame: 10, 20, 30, 40, 50, and 60 minutes
description: Hypertension (SBP > 180) from documented vital signs,hypotension (SBP <90) from documented vital signs, hypoxia (oxygen saturation < 90%), respiratory depression (RR<8 or need for mechanical intervention), nausea, vomiting, symptoms of opiate withdrawal (diarrhea, abdominal pain, diaphoresis)
measure: Pain reduction
time frame: 10, 20, 30, 40, 50, and 60 minutes
description: Pain reduction at each time point. Measured by NRS (time 0) minus NRS (time x)
measure: Successful analgesia
time frame: 60 minutes
description: Proportion of patients with NRS < 3 at 60 minutes
measure: Repeat dosing
time frame: 20 minutes
description: Proportion of patients requiring reducing of analgesia at 20 minutes
measure: Summed Pain Intensity difference
time frame: 60 minutes
description: Measurement combining relief magnitude and duration in a single score
arm group label: Buprenorphine
arm group type: Experimental
description: Patients will receive IV buprenorphine 0.3mg diluted to a volume of 10mL with NS in a plastic syringe administered over 3-5 minutes. At 20 minutes, the patient will be asked "would you like more pain medication?" If he/she answers "yes", then he/she will receive a second dose of IV buprenorphine 0.3mg.
arm group label: Morphine
arm group type: Active Comparator
description: Patients will receive IV morphine 0.1mg/kg (max dose 8mg) diluted to a volume of 10mL with NS in a plastic syringe administered over 3-5 minutes. At 20 minutes, the patient will be asked "would you like more pain medication?" If he/she answers "yes", then he/she will receive a second dose of IV morphine 0.1mg/kg (max dose 8mg).
intervention type: Drug
intervention name: Buprenorphine
description: buprenorphine 0.3mg IV
arm group label: Buprenorphine
intervention type: Drug
intervention name: Morphine Sulfate
description: morphine 0.1 mg/kg IV (max 8mg per dose)
arm group label: Morphine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Duong, MD MS
phone: 510-437-4573
email: dduong@alamedahealthsystem.org
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Alameda Health System
investigator full name: David Duong
investigator title: Principal Investigator
mesh term: Emergencies
mesh term: Morphine
mesh term: Buprenorphine
sharing ipd: No