<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/NCT03017248</url>
  </required_header>
  <id_info>
    <org_study_id>FMSousse</org_study_id>
    <nct_id>NCT03017248</nct_id>
  </id_info>
  <brief_title>Low-dose Ketamine for Acute Pain in the Emergency Department</brief_title>
  <official_title>Benefit of the Association of Low Doses of Ketamine With Intravenous Morphine in the Treatment of Acute Severe Pain in Emergency Department</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Faculty of Medicine, Sousse</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Faculty of Medicine, Sousse</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to determine the efficacy and safety of low dose ketamine in association with&#xD;
      IV morphine in the management of acute moderate to severe pain in emergency department.&#xD;
&#xD;
      The investigators hypothesize that low dose ketamine will result in more effective pain&#xD;
      control than morphine alone and will not be associated with an increase in adverse events.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Management of pain in the Emergency Department is challenging. Treatment of pain is most&#xD;
      often accomplished by parenteral opioids analgesics. However, the use of opioids alone for&#xD;
      pain control is often associated with inadequate analgesia and increased adverse events.&#xD;
&#xD;
      Low-dose ketamine has been shown to improve pain perception and produce an opioid-sparing&#xD;
      effect when given perioperatively.&#xD;
&#xD;
      Its use in the ED may probably play a role in maximizing analgesia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>January 2016</start_date>
  <completion_date type="Anticipated">March 2017</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy of analgesia: To assess the primary outcome of pain relief, we used patient-reported pain scores. We consider the pain decreasing of at least 50% of pain score and the summed pain-intensity difference (SPID) over 2 hours</measure>
    <time_frame>Two hours after starting protocol</time_frame>
    <description>At baseline, to assess our primary aim, efficacy of pain control, we will use patient reported pain scores and amount of rescue analgesia (parenteral morphine) received. Trained residents will ask participants to report their pains scores using a numerical pain rating scale (NPRS). The NPRS used will be a 0 to 10 rating scale. Baseline NPRS will be measured after randomization, but just before administration of morphine. Change in reported pain score during the protocol will be analysed.&#xD;
The SPID was calculated using the pain-intensity difference (PID) at each of these study time points. The PID for a given time point is equal to the baseline NPRS minus the subsequent NPRS at each study time point. SPID is the summation of the PID at each of the study time points, weighted using the amount of time since the prior assessment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total patient-perceived pain relief</measure>
    <time_frame>Two hours after starting protocol</time_frame>
    <description>The total patient-perceived pain relief will be calculated using weighted sum of the pain relief scale performed at each study time point. This pain relief scale is a five-point scale that asks participants to rate pain relief as complete = 4, a lot = 3, some = 2, a little = 1, and none = 0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of rescue analgesia received</measure>
    <time_frame>Two hours after starting protocol</time_frame>
    <description>The amount of rescue analgesia received (in milligrams of morphine equivalents) will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to rescue analgesia</measure>
    <time_frame>Two hours after starting protocol</time_frame>
    <description>Time to rescue analgesia will be calculated as the time from administration of the last study medication (placebo or ketamine) to administration of an opioid analgesic.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The occurrence of adverse events</measure>
    <time_frame>Two hours after starting protocol</time_frame>
    <description>We will record participant-reported dizziness, nausea, vomiting, confusion, dysphoria, visual disturbances, or other complaints at baseline and each study time point. All patients will be monitored for the duration of the study period and vital signs will be recorded at each time point.&#xD;
The presence of tachycardia (heart rate &gt; 100 beats/min.), hypotension (systolic blood pressure [sBP] &lt; 100 mm Hg), hypertension (sBP &gt; 180 mm Hg or diastolic blood pressure [dBP] &gt; 100 mm Hg), and respiratory depression (respiratory rate &lt; 12 breaths/min, oxygen saturation &lt; 92%, or need for supplemental oxygen) will be noted.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The total dose of morphine administered</measure>
    <time_frame>Two hours after starting protocol</time_frame>
    <description>The amount of rescue analgesia will be recorded at each time point and the total dose calculated</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">125</enrollment>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Morphine and Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Morphine IV, Dose: 0.1 mg/Kg followed 10 minutes later by an injection of Placebos (0.9% normal saline 0.05ml/kg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Morphine and Ketamine 0.15</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Morphine IV, Dose: 0.1 mg/Kg followed 10 minutes later by an IV bolus of Ketamine at the dose of 0.15mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Morphine and Ketamine 0.3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Morphine IV, Dose: 0.1 mg/Kg followed 10 minutes later by an IV bolus of Ketamine at the dose of 0.3mg/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>ketamine</description>
    <arm_group_label>Morphine and Ketamine 0.15</arm_group_label>
    <arm_group_label>Morphine and Ketamine 0.3</arm_group_label>
    <other_name>Ketalar, 50 Mg/mL Injectable Solution</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>0.9% normal saline</description>
    <arm_group_label>Morphine and Placebo</arm_group_label>
    <other_name>Normal Saline Flush, 0.9% Injectable Solution</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <description>Morphine</description>
    <arm_group_label>Morphine and Ketamine 0.15</arm_group_label>
    <arm_group_label>Morphine and Ketamine 0.3</arm_group_label>
    <arm_group_label>Morphine and Placebo</arm_group_label>
    <other_name>Morphine Sulfate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to understand and give informed consent&#xD;
&#xD;
          -  Comfortable with the experimental protocol as outlined to them by the research team&#xD;
&#xD;
          -  Severe pain, pain score of at least 50/100 on Visual Analogue Scale (VAS) or 5/10&#xD;
             numerical ratings score&#xD;
&#xD;
          -  Acute pain, pain duration &lt; 7days&#xD;
&#xD;
          -  Deemed by treating ED attending physician to require IV opioid analgesia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Neurologic, respiratory, or hemodynamic compromise&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Known or suspected allergy to ketamine or morphine&#xD;
&#xD;
          -  Known Renal (Cr&gt;2.0) or Liver Failure&#xD;
&#xD;
          -  Unstable psychiatric disease (as per treating physician)&#xD;
&#xD;
          -  History of stroke&#xD;
&#xD;
          -  History of cardiac disease or coronary artery disease&#xD;
&#xD;
          -  History of chronic respiratory disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hajer KRAIEM, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Faculty of medicine of Sousse</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Faculty of medicine of Sousse</name>
      <address>
        <city>Sousse</city>
        <zip>4002</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Tunisia</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>January 29, 2017</last_update_submitted>
  <last_update_submitted_qc>January 29, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 31, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Faculty of Medicine, Sousse</investigator_affiliation>
    <investigator_full_name>HAJER KRAIEM</investigator_full_name>
    <investigator_title>M.D</investigator_title>
  </responsible_party>
  <keyword>pain</keyword>
  <keyword>ketamine</keyword>
  <keyword>morphine</keyword>
  <keyword>analgesia</keyword>
  <keyword>emergency</keyword>
  <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>Ketamine</mesh_term>
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Pharmaceutical Solutions</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03017248
org study id: FMSousse
nct id: NCT03017248
lead sponsor: 
has dmc: Yes
This study aims to determine the efficacy and safety of low dose ketamine in association with
      IV morphine in the management of acute moderate to severe pain in emergency department.

      The investigators hypothesize that low dose ketamine will result in more effective pain
      control than morphine alone and will not be associated with an increase in adverse events.
Management of pain in the Emergency Department is challenging. Treatment of pain is most
      often accomplished by parenteral opioids analgesics. However, the use of opioids alone for
      pain control is often associated with inadequate analgesia and increased adverse events.

      Low-dose ketamine has been shown to improve pain perception and produce an opioid-sparing
      effect when given perioperatively.

      Its use in the ED may probably play a role in maximizing analgesia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Efficacy of analgesia: To assess the primary outcome of pain relief, we used patient-reported pain scores. We consider the pain decreasing of at least 50% of pain score and the summed pain-intensity difference (SPID) over 2 hours
time frame: Two hours after starting protocol
description: At baseline, to assess our primary aim, efficacy of pain control, we will use patient reported pain scores and amount of rescue analgesia (parenteral morphine) received. Trained residents will ask participants to report their pains scores using a numerical pain rating scale (NPRS). The NPRS used will be a 0 to 10 rating scale. Baseline NPRS will be measured after randomization, but just before administration of morphine. Change in reported pain score during the protocol will be analysed.
The SPID was calculated using the pain-intensity difference (PID) at each of these study time points. The PID for a given time point is equal to the baseline NPRS minus the subsequent NPRS at each study time point. SPID is the summation of the PID at each of the study time points, weighted using the amount of time since the prior assessment
measure: Total patient-perceived pain relief
time frame: Two hours after starting protocol
description: The total patient-perceived pain relief will be calculated using weighted sum of the pain relief scale performed at each study time point. This pain relief scale is a five-point scale that asks participants to rate pain relief as complete = 4, a lot = 3, some = 2, a little = 1, and none = 0
measure: Amount of rescue analgesia received
time frame: Two hours after starting protocol
description: The amount of rescue analgesia received (in milligrams of morphine equivalents) will be recorded.
measure: Time to rescue analgesia
time frame: Two hours after starting protocol
description: Time to rescue analgesia will be calculated as the time from administration of the last study medication (placebo or ketamine) to administration of an opioid analgesic.
measure: The occurrence of adverse events
time frame: Two hours after starting protocol
description: We will record participant-reported dizziness, nausea, vomiting, confusion, dysphoria, visual disturbances, or other complaints at baseline and each study time point. All patients will be monitored for the duration of the study period and vital signs will be recorded at each time point.
The presence of tachycardia (heart rate > 100 beats/min.), hypotension (systolic blood pressure [sBP] < 100 mm Hg), hypertension (sBP > 180 mm Hg or diastolic blood pressure [dBP] > 100 mm Hg), and respiratory depression (respiratory rate < 12 breaths/min, oxygen saturation < 92%, or need for supplemental oxygen) will be noted.
measure: The total dose of morphine administered
time frame: Two hours after starting protocol
description: The amount of rescue analgesia will be recorded at each time point and the total dose calculated
arm group label: Morphine and Placebo
arm group type: Active Comparator
description: Morphine IV, Dose: 0.1 mg/Kg followed 10 minutes later by an injection of Placebos (0.9% normal saline 0.05ml/kg)
arm group label: Morphine and Ketamine 0.15
arm group type: Experimental
description: Morphine IV, Dose: 0.1 mg/Kg followed 10 minutes later by an IV bolus of Ketamine at the dose of 0.15mg/kg
arm group label: Morphine and Ketamine 0.3
arm group type: Experimental
description: Morphine IV, Dose: 0.1 mg/Kg followed 10 minutes later by an IV bolus of Ketamine at the dose of 0.3mg/kg
intervention type: Drug
intervention name: Ketamine
description: ketamine
arm group label: Morphine and Ketamine 0.15
arm group label: Morphine and Ketamine 0.3
other name: Ketalar, 50 Mg/mL Injectable Solution
intervention type: Drug
intervention name: Placebos
description: 0.9% normal saline
arm group label: Morphine and Placebo
other name: Normal Saline Flush, 0.9% Injectable Solution
intervention type: Drug
intervention name: Morphine
description: Morphine
arm group label: Morphine and Ketamine 0.15
arm group label: Morphine and Ketamine 0.3
arm group label: Morphine and Placebo
other name: Morphine Sulfate
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Hajer KRAIEM, MD
role: Principal Investigator
affiliation: Faculty of medicine of Sousse
facility: 
country: Tunisia
responsible party type: Principal Investigator
investigator affiliation: Faculty of Medicine, Sousse
investigator full name: HAJER KRAIEM
investigator title: M.D
mesh term: Emergencies
mesh term: Ketamine
mesh term: Morphine
mesh term: Pharmaceutical Solutions
sharing ipd: Undecided