<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/NCT03305055</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00089761</org_study_id>
    <secondary_id>NTI-NTRR15-13</secondary_id>
    <nct_id>NCT03305055</nct_id>
  </id_info>
  <brief_title>RCT: Fentanyl Plus Ketamine Versus Fentanyl Alone for Acute Burn Pain</brief_title>
  <official_title>Evaluating the Safety, Efficacy and Opiate Sparing Effects of Low-Dose, Slow Infusion Ketamine as a Battlefield Analgesic for Acute Pain in Burn Wounds.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United States Department of Defense</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Congressionally Directed Medical Research Programs</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</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 Ketamine for Acute Pain in Burns study is a randomized, double-blind, parallel group&#xD;
      trial (RCT) with active control (usual care) contrasting the efficacy and safety of &quot;Ketamine&#xD;
      Plus Opiate-based usual care&quot; (O+K) with the safety and efficacy of the &quot;Current Standard of&#xD;
      Care&quot;. THe current standard of care is an opiate medication alone, Fentanyl (Usual&#xD;
      Care-Opiate (UC-O), dose/timing as per Burn Center protocol).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Department of Defense (DoD) and the U.S. Army Medical Research and Materiel Command (USAMRMC)&#xD;
      are funding this RCT for the following reasons:&#xD;
&#xD;
      Primary Aims:&#xD;
&#xD;
        1. To evaluate the safety and efficacy of fentanyl (usual care) + placebo versus fentanyl +&#xD;
           ketamine (low-dose, sub-anesthetic, slow-infusion) during twice daily burn wound care&#xD;
           across a 7-day study period and 30 day outcome period.&#xD;
&#xD;
        2. To evaluate the opiate sparing effect of fentanyl (usual care) + placebo versus fentanyl&#xD;
           + ketamine (low-dose, sub-anesthetic, slow-infusion) during the 7-day study period and&#xD;
           30 day outcome period.&#xD;
&#xD;
      and&#xD;
&#xD;
      Secondary Aims:&#xD;
&#xD;
        1. To determine the short and long term effect of the Ketamine Augmentation Condition&#xD;
           versus the Usual Care Condition on symptoms and syndromes of posttraumatic stress&#xD;
           disorder and of depression,&#xD;
&#xD;
        2. To evaluate several established and hypothesized moderators of the relationship between&#xD;
           the Ketamine Augmentation Condition versus the Usual Care Condition on: 1) pain severity&#xD;
           reported during wound care, 2) opiate use during wound care, 3) posttraumatic stress and&#xD;
           4) depression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Funding withdrawn - slow enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">December 16, 2017</start_date>
  <completion_date type="Actual">April 21, 2018</completion_date>
  <primary_completion_date type="Actual">March 28, 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>
    <intervention_model_description>Randomized, placebo-controlled, repeated exposure (twice daily, 7 days), safety and efficacy trial of Usual Care (fentanyl PLUS saline / placebo) versus Usual Care plus Study Drug Augmentation (fentanyl PLUS ketamine) in reducing acute pain severity assessed before, during and after wound care for acute burn injury in the Burn Center of an Academic Medical Center.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Pharmacy receives order from provider and then prepares the study drug in an unmarked, nondescript delivery system (&quot;bag&quot;) and the study drug information is entered from the bag into the pump so that delivery that is timed and volume controlled per study protocol. This is hung next to patient, connected and started. Masked personnel include provider (order study drug protocol), nurse (wound care), data assessor (Research Assistant), and consenting participant (patient with acute burn).</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Wound Care Pain</measure>
    <time_frame>Up to 40 days</time_frame>
    <description>Average Pain across 14 sessions between the 2 groups and related outcome measures up to 40 days following study enrollment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Trajectory of Mean Wound Care Session Pain Within Sessions</measure>
    <time_frame>7-days, within session</time_frame>
    <description>Trajectory of average pain within session</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Trajectory of Mean Wound Care Session Pain Across Sessions</measure>
    <time_frame>7-Days across sessions</time_frame>
    <description>Trajectory of average pain across 7 day study protocol</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Opiate Sparing Effect</measure>
    <time_frame>37 days</time_frame>
    <description>Pro Re Nata (PRN) pain management or adjunct expressed in opiate equivalents (e.g., anxiolytic) or premed (e.g., non-protocol medications for pain, anxiety, etc); post-session (1 and 6 hours post session , e.g., pain, anxiolytic, etc).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Post Traumatic Stress Disorder (PTSD) Symptoms as Assessed by Davidson Trauma Scale</measure>
    <time_frame>37 days</time_frame>
    <description>PTSD symptoms score as assessed by Davidson Trauma Scale consisting of 17 items (symptoms) with each item measured for severity and frequency. Each item is rated 0 - 4. Overall score ranges from 0 to 136, with higher scores indicating higher frequency and severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depression Symptoms as Assessed by the Patient Health Questionnaire</measure>
    <time_frame>37 days</time_frame>
    <description>Severity and trajectory of depression symptoms as assessed by the Patient Health Questionnaire (PHQ) 9. The questionnaire has 9 items with each rated from 0 to 3. Overall scores ranges from 0 to 27 with 1-4 being minimal depression, 5-9 being mild depression, 10-14 being moderate depression, 15-19 being moderately severe depression and 20-27 being severe depression.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Acute Pain</condition>
  <condition>Wound Care</condition>
  <condition>Posttraumatic Stress Disorder</condition>
  <arm_group>
    <arm_group_label>Fentanyl Plus Ketamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study drug group&#xD;
Ketamine Loading Dose (Low Dose, Slow Infusion) =&#xD;
• 0.3 mg/kg; Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, … Then,&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg. This is given to participants in both Group 1 and Group 2 initiated &lt; 1 minute prior to wound care.&#xD;
Ketamine (Study Drug, Infusion) = • 2.5 mcg/kg/min, Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
Fentanyl PRN dose* = 1 mcg / kg. Provided when participant requires additional pain medication.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fentanyl Plus Saline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Usual care group&#xD;
Saline Loading Dose (Low Dose, Slow Infusion) =&#xD;
• An identical volume of saline as that in 0.3 mg/kg of ketamine. Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, (i.e., same time/rate as STUDY DRUG GROUP receives ketamine loading dose), … Then, ...&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg: This is given to participants in both Group 1 and Group 2 initiated &lt;1 minute prior to wound care.&#xD;
Saline (Placebo, Infusion) = • Identical volume of fluid as that in 2.5 mcg/kg/min of ketamine; Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
FENTANYL PRN DOSE = 1 mcg / kg. Provided when participant requires additional pain medication.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ketamine</intervention_name>
    <description>Information included in arm descriptions</description>
    <arm_group_label>Fentanyl Plus Ketamine</arm_group_label>
    <other_name>STUDY DRUG GROUP (Fentanyl plus Ketamine)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl</intervention_name>
    <description>Information included in arm descriptions</description>
    <arm_group_label>Fentanyl Plus Ketamine</arm_group_label>
    <arm_group_label>Fentanyl Plus Saline</arm_group_label>
    <other_name>USUAL CARE GROUP (Fentanyl plus saline/placebo)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Total Body Surface Area (TBSA) greater than or equal to 2%; Less than or equal to 40%&#xD;
             TBSA&#xD;
&#xD;
          -  English speaking&#xD;
&#xD;
          -  pain in emergency room during initial wound evaluation (on admission) greater than 5&#xD;
             /10&#xD;
&#xD;
          -  estimated length of stay greater than or equal to 5 days&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  requiring endotracheal intubation and sedation,&#xD;
&#xD;
          -  severe hearing impairment,&#xD;
&#xD;
          -  cognitive impairment status - Mini-Mental State Examination (MMSE) &lt;/=20,&#xD;
&#xD;
          -  diminished capacity unable to provide informed consent;&#xD;
&#xD;
          -  Past Medical History (PMH): insensate (eg. spinal cord injury, peripheral neuropathy)&#xD;
&#xD;
          -  Safety: contraindication (e.g., potential drug interactions or medical comorbidities)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James A Fauerbach, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University SOM</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kevin Gerold, DOJD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University SOM</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Julie Caffrey, DO</last_name>
    <role>Study Director</role>
    <affiliation>Johns Hopkins University SOM</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Johns Hopkins Burn Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>June 12, 2017</study_first_submitted>
  <study_first_submitted_qc>October 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 9, 2017</study_first_posted>
  <results_first_submitted>February 18, 2019</results_first_submitted>
  <results_first_submitted_qc>February 18, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">March 12, 2019</results_first_posted>
  <last_update_submitted>February 18, 2019</last_update_submitted>
  <last_update_submitted_qc>February 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>opioid</keyword>
  <keyword>ketamine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Pain</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Plan not operationalized as yet.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data will become available by 1 year after final data publication and remain available for indefinitely.</ipd_time_frame>
    <ipd_access_criteria>Written request from faculty investigator to PI or Study Director specifying planned safety &amp; monitoring plan and data analytic aims and hypotheses</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 17, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT03305055/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Fentanyl Plus Ketamine</title>
          <description>Study drug group&#xD;
Ketamine Loading Dose (Low Dose, Slow Infusion) =&#xD;
• 0.3 mg/kg; Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, … Then,&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg. This is given to participants in both Group 1 and Group 2 initiated &lt; 1 minute prior to wound care.&#xD;
Ketamine (Study Drug, Infusion) = • 2.5 mcg/kg/min, Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
Fentanyl PRN dose* = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
ketamine: Information included in arm descriptions&#xD;
Fentanyl: Information included in arm descriptions</description>
        </group>
        <group group_id="P2">
          <title>Fentanyl Plus Saline</title>
          <description>Usual care group&#xD;
Saline Loading Dose (Low Dose, Slow Infusion) =&#xD;
• An identical volume of saline as that in 0.3 mg/kg of ketamine. Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, (i.e., same time/rate as STUDY DRUG GROUP receives ketamine loading dose), … Then, ...&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg: This is given to participants in both Group 1 and Group 2 initiated &lt;1 minute prior to wound care.&#xD;
Saline (Placebo, Infusion) = • Identical volume of fluid as that in 2.5 mcg/kg/min of ketamine; Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
FENTANYL PRN DOSE = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
Fentanyl: Information included in arm descriptions</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Fentanyl Plus Ketamine</title>
          <description>Study drug group&#xD;
Ketamine Loading Dose (Low Dose, Slow Infusion) =&#xD;
• 0.3 mg/kg; Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, … Then,&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg. This is given to participants in both Group 1 and Group 2 initiated &lt; 1 minute prior to wound care.&#xD;
Ketamine (Study Drug, Infusion) = • 2.5 mcg/kg/min, Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
Fentanyl PRN dose* = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
ketamine: Information included in arm descriptions&#xD;
Fentanyl: Information included in arm descriptions</description>
        </group>
        <group group_id="B2">
          <title>Fentanyl Plus Saline</title>
          <description>Usual care group&#xD;
Saline Loading Dose (Low Dose, Slow Infusion) =&#xD;
• An identical volume of saline as that in 0.3 mg/kg of ketamine. Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, (i.e., same time/rate as STUDY DRUG GROUP receives ketamine loading dose), … Then, ...&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg: This is given to participants in both Group 1 and Group 2 initiated &lt;1 minute prior to wound care.&#xD;
Saline (Placebo, Infusion) = • Identical volume of fluid as that in 2.5 mcg/kg/min of ketamine; Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
FENTANYL PRN DOSE = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
Fentanyl: Information included in arm descriptions</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2"/>
            <count group_id="B2" value="2"/>
            <count group_id="B3" value="4"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44" spread="35.4"/>
                    <measurement group_id="B2" value="37" spread="15.6"/>
                    <measurement group_id="B3" value="40.5" spread="22.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Wound Care Pain</title>
        <description>Average Pain across 14 sessions between the 2 groups and related outcome measures up to 40 days following study enrollment.</description>
        <time_frame>Up to 40 days</time_frame>
        <population>Data was not collected for the minimum threshold [per the statistical analysis plan] of 6-11 consecutive wound care sessions to assess this outcome measure</population>
        <group_list>
          <group group_id="O1">
            <title>Fentanyl Plus Ketamine</title>
            <description>Study drug group&#xD;
Ketamine Loading Dose (Low Dose, Slow Infusion) =&#xD;
• 0.3 mg/kg; Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, … Then,&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg. This is given to participants in both Group 1 and Group 2 initiated &lt; 1 minute prior to wound care.&#xD;
Ketamine (Study Drug, Infusion) = • 2.5 mcg/kg/min, Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
Fentanyl PRN dose* = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
ketamine: Information included in arm descriptions&#xD;
Fentanyl: Information included in arm descriptions</description>
          </group>
          <group group_id="O2">
            <title>Fentanyl Plus Saline</title>
            <description>Usual care group&#xD;
Saline Loading Dose (Low Dose, Slow Infusion) =&#xD;
• An identical volume of saline as that in 0.3 mg/kg of ketamine. Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, (i.e., same time/rate as STUDY DRUG GROUP receives ketamine loading dose), … Then, ...&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg: This is given to participants in both Group 1 and Group 2 initiated &lt;1 minute prior to wound care.&#xD;
Saline (Placebo, Infusion) = • Identical volume of fluid as that in 2.5 mcg/kg/min of ketamine; Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
FENTANYL PRN DOSE = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
Fentanyl: Information included in arm descriptions</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Wound Care Pain</title>
          <description>Average Pain across 14 sessions between the 2 groups and related outcome measures up to 40 days following study enrollment.</description>
          <population>Data was not collected for the minimum threshold [per the statistical analysis plan] of 6-11 consecutive wound care sessions to assess this outcome measure</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Trajectory of Mean Wound Care Session Pain Within Sessions</title>
        <description>Trajectory of average pain within session</description>
        <time_frame>7-days, within session</time_frame>
        <population>Data was not collected for the minimum threshold [per the statistical analysis plan] of 6-11 consecutive wound care sessions to assess this outcome measure</population>
        <group_list>
          <group group_id="O1">
            <title>Fentanyl Plus Ketamine</title>
            <description>Study drug group&#xD;
Ketamine Loading Dose (Low Dose, Slow Infusion) =&#xD;
• 0.3 mg/kg; Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, … Then,&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg. This is given to participants in both Group 1 and Group 2 initiated &lt; 1 minute prior to wound care.&#xD;
Ketamine (Study Drug, Infusion) = • 2.5 mcg/kg/min, Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
Fentanyl PRN dose* = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
ketamine: Information included in arm descriptions&#xD;
Fentanyl: Information included in arm descriptions</description>
          </group>
          <group group_id="O2">
            <title>Fentanyl Plus Saline</title>
            <description>Usual care group&#xD;
Saline Loading Dose (Low Dose, Slow Infusion) =&#xD;
• An identical volume of saline as that in 0.3 mg/kg of ketamine. Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, (i.e., same time/rate as STUDY DRUG GROUP receives ketamine loading dose), … Then, ...&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg: This is given to participants in both Group 1 and Group 2 initiated &lt;1 minute prior to wound care.&#xD;
Saline (Placebo, Infusion) = • Identical volume of fluid as that in 2.5 mcg/kg/min of ketamine; Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
FENTANYL PRN DOSE = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
Fentanyl: Information included in arm descriptions</description>
          </group>
        </group_list>
        <measure>
          <title>Trajectory of Mean Wound Care Session Pain Within Sessions</title>
          <description>Trajectory of average pain within session</description>
          <population>Data was not collected for the minimum threshold [per the statistical analysis plan] of 6-11 consecutive wound care sessions to assess this outcome measure</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Trajectory of Mean Wound Care Session Pain Across Sessions</title>
        <description>Trajectory of average pain across 7 day study protocol</description>
        <time_frame>7-Days across sessions</time_frame>
        <population>Data was not collected for the minimum threshold [per the statistical analysis plan] of 6-11 consecutive wound care sessions to assess this outcome measure</population>
        <group_list>
          <group group_id="O1">
            <title>Fentanyl Plus Ketamine</title>
            <description>Study drug group&#xD;
Ketamine Loading Dose (Low Dose, Slow Infusion) =&#xD;
• 0.3 mg/kg; Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, … Then,&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg. This is given to participants in both Group 1 and Group 2 initiated &lt; 1 minute prior to wound care.&#xD;
Ketamine (Study Drug, Infusion) = • 2.5 mcg/kg/min, Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
Fentanyl PRN dose* = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
ketamine: Information included in arm descriptions&#xD;
Fentanyl: Information included in arm descriptions</description>
          </group>
          <group group_id="O2">
            <title>Fentanyl Plus Saline</title>
            <description>Usual care group&#xD;
Saline Loading Dose (Low Dose, Slow Infusion) =&#xD;
• An identical volume of saline as that in 0.3 mg/kg of ketamine. Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, (i.e., same time/rate as STUDY DRUG GROUP receives ketamine loading dose), … Then, ...&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg: This is given to participants in both Group 1 and Group 2 initiated &lt;1 minute prior to wound care.&#xD;
Saline (Placebo, Infusion) = • Identical volume of fluid as that in 2.5 mcg/kg/min of ketamine; Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
FENTANYL PRN DOSE = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
Fentanyl: Information included in arm descriptions</description>
          </group>
        </group_list>
        <measure>
          <title>Trajectory of Mean Wound Care Session Pain Across Sessions</title>
          <description>Trajectory of average pain across 7 day study protocol</description>
          <population>Data was not collected for the minimum threshold [per the statistical analysis plan] of 6-11 consecutive wound care sessions to assess this outcome measure</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Opiate Sparing Effect</title>
        <description>Pro Re Nata (PRN) pain management or adjunct expressed in opiate equivalents (e.g., anxiolytic) or premed (e.g., non-protocol medications for pain, anxiety, etc); post-session (1 and 6 hours post session , e.g., pain, anxiolytic, etc).</description>
        <time_frame>37 days</time_frame>
        <population>Data was not collected for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Fentanyl Plus Ketamine</title>
            <description>Study drug group&#xD;
Ketamine Loading Dose (Low Dose, Slow Infusion) =&#xD;
• 0.3 mg/kg; Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, … Then,&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg. This is given to participants in both Group 1 and Group 2 initiated &lt; 1 minute prior to wound care.&#xD;
Ketamine (Study Drug, Infusion) = • 2.5 mcg/kg/min, Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
Fentanyl PRN dose* = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
ketamine: Information included in arm descriptions&#xD;
Fentanyl: Information included in arm descriptions</description>
          </group>
          <group group_id="O2">
            <title>Fentanyl Plus Saline</title>
            <description>Usual care group&#xD;
Saline Loading Dose (Low Dose, Slow Infusion) =&#xD;
• An identical volume of saline as that in 0.3 mg/kg of ketamine. Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, (i.e., same time/rate as STUDY DRUG GROUP receives ketamine loading dose), … Then, ...&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg: This is given to participants in both Group 1 and Group 2 initiated &lt;1 minute prior to wound care.&#xD;
Saline (Placebo, Infusion) = • Identical volume of fluid as that in 2.5 mcg/kg/min of ketamine; Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
FENTANYL PRN DOSE = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
Fentanyl: Information included in arm descriptions</description>
          </group>
        </group_list>
        <measure>
          <title>Opiate Sparing Effect</title>
          <description>Pro Re Nata (PRN) pain management or adjunct expressed in opiate equivalents (e.g., anxiolytic) or premed (e.g., non-protocol medications for pain, anxiety, etc); post-session (1 and 6 hours post session , e.g., pain, anxiolytic, etc).</description>
          <population>Data was not collected for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Post Traumatic Stress Disorder (PTSD) Symptoms as Assessed by Davidson Trauma Scale</title>
        <description>PTSD symptoms score as assessed by Davidson Trauma Scale consisting of 17 items (symptoms) with each item measured for severity and frequency. Each item is rated 0 - 4. Overall score ranges from 0 to 136, with higher scores indicating higher frequency and severity.</description>
        <time_frame>37 days</time_frame>
        <population>Data was not collected for the minimum threshold [per the statistical analysis plan] of 6-11 consecutive wound care sessions to assess this outcome measure</population>
        <group_list>
          <group group_id="O1">
            <title>Fentanyl Plus Ketamine</title>
            <description>Study drug group&#xD;
Ketamine Loading Dose (Low Dose, Slow Infusion) =&#xD;
• 0.3 mg/kg; Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, … Then,&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg. This is given to participants in both Group 1 and Group 2 initiated &lt; 1 minute prior to wound care.&#xD;
Ketamine (Study Drug, Infusion) = • 2.5 mcg/kg/min, Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
Fentanyl PRN dose* = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
ketamine: Information included in arm descriptions&#xD;
Fentanyl: Information included in arm descriptions</description>
          </group>
          <group group_id="O2">
            <title>Fentanyl Plus Saline</title>
            <description>Usual care group&#xD;
Saline Loading Dose (Low Dose, Slow Infusion) =&#xD;
• An identical volume of saline as that in 0.3 mg/kg of ketamine. Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, (i.e., same time/rate as STUDY DRUG GROUP receives ketamine loading dose), … Then, ...&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg: This is given to participants in both Group 1 and Group 2 initiated &lt;1 minute prior to wound care.&#xD;
Saline (Placebo, Infusion) = • Identical volume of fluid as that in 2.5 mcg/kg/min of ketamine; Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
FENTANYL PRN DOSE = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
Fentanyl: Information included in arm descriptions</description>
          </group>
        </group_list>
        <measure>
          <title>Post Traumatic Stress Disorder (PTSD) Symptoms as Assessed by Davidson Trauma Scale</title>
          <description>PTSD symptoms score as assessed by Davidson Trauma Scale consisting of 17 items (symptoms) with each item measured for severity and frequency. Each item is rated 0 - 4. Overall score ranges from 0 to 136, with higher scores indicating higher frequency and severity.</description>
          <population>Data was not collected for the minimum threshold [per the statistical analysis plan] of 6-11 consecutive wound care sessions to assess this outcome measure</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Depression Symptoms as Assessed by the Patient Health Questionnaire</title>
        <description>Severity and trajectory of depression symptoms as assessed by the Patient Health Questionnaire (PHQ) 9. The questionnaire has 9 items with each rated from 0 to 3. Overall scores ranges from 0 to 27 with 1-4 being minimal depression, 5-9 being mild depression, 10-14 being moderate depression, 15-19 being moderately severe depression and 20-27 being severe depression.</description>
        <time_frame>37 days</time_frame>
        <population>Data was not collected for the minimum threshold [per the statistical analysis plan] of 6-11 consecutive wound care sessions to assess this outcome measure</population>
        <group_list>
          <group group_id="O1">
            <title>Fentanyl Plus Ketamine</title>
            <description>Study drug group&#xD;
Ketamine Loading Dose (Low Dose, Slow Infusion) =&#xD;
• 0.3 mg/kg; Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, … Then,&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg. This is given to participants in both Group 1 and Group 2 initiated &lt; 1 minute prior to wound care.&#xD;
Ketamine (Study Drug, Infusion) = • 2.5 mcg/kg/min, Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
Fentanyl PRN dose* = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
ketamine: Information included in arm descriptions&#xD;
Fentanyl: Information included in arm descriptions</description>
          </group>
          <group group_id="O2">
            <title>Fentanyl Plus Saline</title>
            <description>Usual care group&#xD;
Saline Loading Dose (Low Dose, Slow Infusion) =&#xD;
• An identical volume of saline as that in 0.3 mg/kg of ketamine. Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, (i.e., same time/rate as STUDY DRUG GROUP receives ketamine loading dose), … Then, ...&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg: This is given to participants in both Group 1 and Group 2 initiated &lt;1 minute prior to wound care.&#xD;
Saline (Placebo, Infusion) = • Identical volume of fluid as that in 2.5 mcg/kg/min of ketamine; Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
FENTANYL PRN DOSE = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
Fentanyl: Information included in arm descriptions</description>
          </group>
        </group_list>
        <measure>
          <title>Depression Symptoms as Assessed by the Patient Health Questionnaire</title>
          <description>Severity and trajectory of depression symptoms as assessed by the Patient Health Questionnaire (PHQ) 9. The questionnaire has 9 items with each rated from 0 to 3. Overall scores ranges from 0 to 27 with 1-4 being minimal depression, 5-9 being mild depression, 10-14 being moderate depression, 15-19 being moderately severe depression and 20-27 being severe depression.</description>
          <population>Data was not collected for the minimum threshold [per the statistical analysis plan] of 6-11 consecutive wound care sessions to assess this outcome measure</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>End of study (approximately 37 days)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Fentanyl Plus Ketamine</title>
          <description>Study drug group&#xD;
Ketamine Loading Dose (Low Dose, Slow Infusion) =&#xD;
• 0.3 mg/kg; Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, … Then,&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg. This is given to participants in both Group 1 and Group 2 initiated &lt; 1 minute prior to wound care.&#xD;
Ketamine (Study Drug, Infusion) = • 2.5 mcg/kg/min, Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
Fentanyl PRN dose* = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
ketamine: Information included in arm descriptions&#xD;
Fentanyl: Information included in arm descriptions</description>
        </group>
        <group group_id="E2">
          <title>Fentanyl Plus Saline</title>
          <description>Usual care group&#xD;
Saline Loading Dose (Low Dose, Slow Infusion) =&#xD;
• An identical volume of saline as that in 0.3 mg/kg of ketamine. Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, (i.e., same time/rate as STUDY DRUG GROUP receives ketamine loading dose), … Then, ...&#xD;
Fentanyl Loading Dose (UC, injection) =&#xD;
• 1 mcg / kg: This is given to participants in both Group 1 and Group 2 initiated &lt;1 minute prior to wound care.&#xD;
Saline (Placebo, Infusion) = • Identical volume of fluid as that in 2.5 mcg/kg/min of ketamine; Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.&#xD;
FENTANYL PRN DOSE = 1 mcg / kg. Provided when participant requires additional pain medication.&#xD;
Fentanyl: Information included in arm descriptions</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain at wound site</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>James A. Fauerbach</name_or_title>
      <organization>Johns Hopkins University</organization>
      <phone>410-550-0890</phone>
      <email>jfauerb1@jhmi.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03305055
org study id: IRB00089761
secondary id: NTI-NTRR15-13
nct id: NCT03305055
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The Ketamine for Acute Pain in Burns study is a randomized, double-blind, parallel group
      trial (RCT) with active control (usual care) contrasting the efficacy and safety of "Ketamine
      Plus Opiate-based usual care" (O+K) with the safety and efficacy of the "Current Standard of
      Care". THe current standard of care is an opiate medication alone, Fentanyl (Usual
      Care-Opiate (UC-O), dose/timing as per Burn Center protocol).
Department of Defense (DoD) and the U.S. Army Medical Research and Materiel Command (USAMRMC)
      are funding this RCT for the following reasons:

      Primary Aims:

        1. To evaluate the safety and efficacy of fentanyl (usual care) + placebo versus fentanyl +
           ketamine (low-dose, sub-anesthetic, slow-infusion) during twice daily burn wound care
           across a 7-day study period and 30 day outcome period.

        2. To evaluate the opiate sparing effect of fentanyl (usual care) + placebo versus fentanyl
           + ketamine (low-dose, sub-anesthetic, slow-infusion) during the 7-day study period and
           30 day outcome period.

      and

      Secondary Aims:

        1. To determine the short and long term effect of the Ketamine Augmentation Condition
           versus the Usual Care Condition on symptoms and syndromes of posttraumatic stress
           disorder and of depression,

        2. To evaluate several established and hypothesized moderators of the relationship between
           the Ketamine Augmentation Condition versus the Usual Care Condition on: 1) pain severity
           reported during wound care, 2) opiate use during wound care, 3) posttraumatic stress and
           4) depression.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, placebo-controlled, repeated exposure (twice daily, 7 days), safety and efficacy trial of Usual Care (fentanyl PLUS saline / placebo) versus Usual Care plus Study Drug Augmentation (fentanyl PLUS ketamine) in reducing acute pain severity assessed before, during and after wound care for acute burn injury in the Burn Center of an Academic Medical Center.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Pharmacy receives order from provider and then prepares the study drug in an unmarked, nondescript delivery system ("bag") and the study drug information is entered from the bag into the pump so that delivery that is timed and volume controlled per study protocol. This is hung next to patient, connected and started. Masked personnel include provider (order study drug protocol), nurse (wound care), data assessor (Research Assistant), and consenting participant (patient with acute burn).
measure: Mean Wound Care Pain
time frame: Up to 40 days
description: Average Pain across 14 sessions between the 2 groups and related outcome measures up to 40 days following study enrollment.
measure: Trajectory of Mean Wound Care Session Pain Within Sessions
time frame: 7-days, within session
description: Trajectory of average pain within session
measure: Trajectory of Mean Wound Care Session Pain Across Sessions
time frame: 7-Days across sessions
description: Trajectory of average pain across 7 day study protocol
measure: Opiate Sparing Effect
time frame: 37 days
description: Pro Re Nata (PRN) pain management or adjunct expressed in opiate equivalents (e.g., anxiolytic) or premed (e.g., non-protocol medications for pain, anxiety, etc); post-session (1 and 6 hours post session , e.g., pain, anxiolytic, etc).
measure: Post Traumatic Stress Disorder (PTSD) Symptoms as Assessed by Davidson Trauma Scale
time frame: 37 days
description: PTSD symptoms score as assessed by Davidson Trauma Scale consisting of 17 items (symptoms) with each item measured for severity and frequency. Each item is rated 0 - 4. Overall score ranges from 0 to 136, with higher scores indicating higher frequency and severity.
measure: Depression Symptoms as Assessed by the Patient Health Questionnaire
time frame: 37 days
description: Severity and trajectory of depression symptoms as assessed by the Patient Health Questionnaire (PHQ) 9. The questionnaire has 9 items with each rated from 0 to 3. Overall scores ranges from 0 to 27 with 1-4 being minimal depression, 5-9 being mild depression, 10-14 being moderate depression, 15-19 being moderately severe depression and 20-27 being severe depression.
arm group label: Fentanyl Plus Ketamine
arm group type: Experimental
description: Study drug group
Ketamine Loading Dose (Low Dose, Slow Infusion) =
• 0.3 mg/kg; Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, … Then,
Fentanyl Loading Dose (UC, injection) =
• 1 mcg / kg. This is given to participants in both Group 1 and Group 2 initiated < 1 minute prior to wound care.
Ketamine (Study Drug, Infusion) = • 2.5 mcg/kg/min, Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.
Fentanyl PRN dose* = 1 mcg / kg. Provided when participant requires additional pain medication.
arm group label: Fentanyl Plus Saline
arm group type: Active Comparator
description: Usual care group
Saline Loading Dose (Low Dose, Slow Infusion) =
• An identical volume of saline as that in 0.3 mg/kg of ketamine. Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, (i.e., same time/rate as STUDY DRUG GROUP receives ketamine loading dose), … Then, ...
Fentanyl Loading Dose (UC, injection) =
• 1 mcg / kg: This is given to participants in both Group 1 and Group 2 initiated <1 minute prior to wound care.
Saline (Placebo, Infusion) = • Identical volume of fluid as that in 2.5 mcg/kg/min of ketamine; Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion.
FENTANYL PRN DOSE = 1 mcg / kg. Provided when participant requires additional pain medication.
intervention type: Drug
intervention name: ketamine
description: Information included in arm descriptions
arm group label: Fentanyl Plus Ketamine
other name: STUDY DRUG GROUP (Fentanyl plus Ketamine)
intervention type: Drug
intervention name: Fentanyl
description: Information included in arm descriptions
arm group label: Fentanyl Plus Ketamine
arm group label: Fentanyl Plus Saline
other name: USUAL CARE GROUP (Fentanyl plus saline/placebo)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: James A Fauerbach, PhD
role: Principal Investigator
affiliation: Johns Hopkins University SOM
last name: Kevin Gerold, DOJD
role: Principal Investigator
affiliation: Johns Hopkins University SOM
last name: Julie Caffrey, DO
role: Study Director
affiliation: Johns Hopkins University SOM
facility: 
country: United States
responsible party type: Sponsor
mesh term: Acute Pain
mesh term: Stress Disorders, Post-Traumatic
mesh term: Fentanyl
mesh term: Ketamine
sharing ipd: Yes
ipd description: Plan not operationalized as yet.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data will become available by 1 year after final data publication and remain available for indefinitely.
ipd access criteria: Written request from faculty investigator to PI or Study Director specifying planned safety & monitoring plan and data analytic aims and hypotheses
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 