<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/NCT03233035</url>
  </required_header>
  <id_info>
    <org_study_id>Ket-Int-Nas-TR</org_study_id>
    <nct_id>NCT03233035</nct_id>
  </id_info>
  <brief_title>Low Dose Ketamine Intra Nasal Traumatology</brief_title>
  <acronym>Ket</acronym>
  <official_title>Intranasal Ketamine for Treatment of Acute Pain in the Emergency Department : A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Monastir</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Monastir</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the efficacy and safety of early administration of low-dose intranasal ketamine&#xD;
      analgesic agents in patients with moderate to severe pain in the ED in reducing the need for&#xD;
      opioid or non opioids analgesic agents.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intranasal ketamine for treatment of acute pain in the emergency department : A randomized&#xD;
      controlled trial&#xD;
&#xD;
      Introduction :&#xD;
&#xD;
      Pain is the most common complaint for emergency department (ED) visits [1].The provision of&#xD;
      adequate, safe, and timely analgesia is a core component of patient care in the emergency&#xD;
      department (ED). Ketamine is a noncompetitive Nmethyl- D-aspartate and glutamate receptor&#xD;
      antagonist that decreases central sensitization, &quot;wind-up&quot; phenomena, and pain memory [2,3].&#xD;
&#xD;
      At subdissociative doses (0.1 to 0.6 mg/kg; most commonly 0.3 mg/kg) maintains potent&#xD;
      analgesic and amnestic effects that are accompanied by preservation of protective airway&#xD;
      reflexes, spontaneous respiration, and cardiopulmonary stability [4-6].&#xD;
&#xD;
      Intranasal route ….&#xD;
&#xD;
      Objective of the study :&#xD;
&#xD;
      To evaluate the efficacy and safety of early administration of low-dose intranasal ketamine&#xD;
      analgesic agents in patients with moderate to severe pain in the ED in reducing the need for&#xD;
      opioid or class III analgesic agents.&#xD;
&#xD;
      Materials and Methods :&#xD;
&#xD;
      Study design :&#xD;
&#xD;
      It is a ramdomized, prospective, double blind, controlled, multicentric trial. The study is&#xD;
      registered with clinical.tria.gov (…….).&#xD;
&#xD;
      Study Setting and Selection of Participants :&#xD;
&#xD;
      The trial is conducted in three community teaching hospitals :&#xD;
&#xD;
        -  Emergency department, fattouma bourguiba university hospital, monastir, tunisia&#xD;
&#xD;
        -  Emergency department, sahloul university hospital, sousse, tunisia&#xD;
&#xD;
        -  Emergency department, farhat hached university hospital, sousse, tunisia&#xD;
&#xD;
      ED principal investigators maintain the randomization list, which is generated before the&#xD;
      start of the study, prepare the medication, and deliver it to the treating physician in a&#xD;
      blinded manner.&#xD;
&#xD;
      Inclusion criteria :&#xD;
&#xD;
      The study includes patients aged 18 to 80 years who presented to the ED with acute limb&#xD;
      trauma pain with a visual analogue scale (VAS) of 5 or more on a standard 11- point (0 to&#xD;
      10). An informed consent is necessary.&#xD;
&#xD;
      Exclusion criteria :&#xD;
&#xD;
        -  Pregnancy,&#xD;
&#xD;
        -  Breast-feeding,&#xD;
&#xD;
        -  Altered mental status,&#xD;
&#xD;
        -  Allergy to ketamine or morphine or&#xD;
&#xD;
        -  Weight less than 46 kg or greater than 115 kg,&#xD;
&#xD;
        -  Unstable vital signs (systolic blood pressure &lt;90 or &gt;180 mm Hg, pulse rate &lt;50 or &gt;150&#xD;
           beats/min, and respiration rate &lt;10 or &gt;30 breaths/min),&#xD;
&#xD;
        -  Medical history of acute head or eye injury, seizure, intracranial hypertension, chronic&#xD;
           pain, severre renal or hepatic insufficiency,&#xD;
&#xD;
        -  Alcohol or drug abuse,&#xD;
&#xD;
        -  Psychiatric illness,&#xD;
&#xD;
        -  Recent (4 hours before) analgesic agent use.&#xD;
&#xD;
      Protocol :&#xD;
&#xD;
      In the triage area, each patient having the inclusion criteria receives 25mg of ketamine in&#xD;
      0.5 ml of serum saline in one pulverisation per nostril or 0.5 mL of normal saline solution&#xD;
      in one pulverisation per nostril as a placebo according to the predetermined randomization&#xD;
      list. None of the treating physician or nurses is aware about the medication received. In all&#xD;
      patients included, the investigators collect vital signs ; demographic and clinical data.&#xD;
&#xD;
      Study investigators record VAS, and adverse effects at 15, 30, 60, 90, and 120 minutes.&#xD;
&#xD;
      At 30 minutes, if patients report a pain numeric rating scale score of 5 or greater and&#xD;
      request additional pain relief, titrated morphine is administered as a rescue analgesic with&#xD;
      a dose of 0.1 mg/Kg repeated every 3 to 5 minutes if the pain numeric rating scale score is&#xD;
      still greater or equal to 3.&#xD;
&#xD;
      All data recorded on data collection sheets, including sex, demographics, medical history,&#xD;
      and vital signs, were entered into SPSS (version 20.0; IBM Corp) by the research manager.&#xD;
&#xD;
      Patients's informed consent is obtained. The ethic commitee of our institution approved the&#xD;
      study.&#xD;
&#xD;
      Endpoints :&#xD;
&#xD;
      Primary endpoints :&#xD;
&#xD;
      - Need for rescue opioids during ED stay&#xD;
&#xD;
      Secondary endpoints :&#xD;
&#xD;
        -  requirement of non-opioids analgesic agents.&#xD;
&#xD;
        -  percentage of patients discharged from the ED with VAS &lt;30.&#xD;
&#xD;
        -  Safety : adverse events&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Actual">December 1, 2018</completion_date>
  <primary_completion_date type="Actual">December 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>
    <intervention_model_description>Double Blind Study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Ketamine versus placebo as a double blind study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number and percentage of patients who need rescue opiods in the two groups</measure>
    <time_frame>30 minutes</time_frame>
    <description>the need for rescue opioids during ED stay</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intolerance to treatement and adverse events</measure>
    <time_frame>30 minutes and at 120 minutes</time_frame>
    <description>Noticing any sign of intolerance due to treatement : Dizziness , Vomiting..</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with VAS &lt;30 mm at discharge</measure>
    <time_frame>120 minutes</time_frame>
    <description>percentage of patients discharged from the ED with VAS &lt;30.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and percentage of patients who required non opiods analgesics</measure>
    <time_frame>30 minutes</time_frame>
    <description>Requirement of non-opioids analgesic agents</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1102</enrollment>
  <condition>Trauma</condition>
  <arm_group>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intranasal placebo pulverisation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ketamine group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intranasal ketamine pulverisation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>25mg of ketamine in 0.5 ml of serum saline in one pulverisation per nostril is received</description>
    <arm_group_label>Ketamine group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>0.5 mL of normal saline solution as a placebo in one pulverisation per nostril</description>
    <arm_group_label>placebo group</arm_group_label>
    <other_name>normal saline solution</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The study includes patients aged 18 to 80 years who presented to the ED with acute&#xD;
             limb trauma pain with a visual analgesic scale (VAS) of 5 or more on a standard 11-&#xD;
             point (0 to 10). An informed consent is necessary.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  - Pregnancy,&#xD;
&#xD;
          -  Breast-feeding,&#xD;
&#xD;
          -  Altered mental status,&#xD;
&#xD;
          -  Allergy to ketamine or morphine or&#xD;
&#xD;
          -  Weight less than 46 kg or greater than 115 kg,&#xD;
&#xD;
          -  Unstable vital signs (systolic blood pressure &lt;90 or &gt;180 mm Hg, pulse rate &lt;50 or&#xD;
             &gt;150 beats/min, and respiration rate &lt;10 or &gt;30 breaths/min),&#xD;
&#xD;
          -  Medical history of acute head or eye injury, seizure, intracranial hypertension,&#xD;
             chronic pain, severre renal or hepatic insufficiency,&#xD;
&#xD;
          -  Alcohol or drug abuse,&#xD;
&#xD;
          -  Psychiatric illness,&#xD;
&#xD;
          -  Recent (4 hours before) analgesic agent use.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nouira Semir, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>university Hospital of Monastir</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nouira Samir</name>
      <address>
        <city>Monastir</city>
        <state>Emergency Department Monastir, Tunisia 5000</state>
        <zip>5000</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emergency department of university hospital Fattouma Bourguiba of Monastir</name>
      <address>
        <city>Monastir</city>
        <zip>5000</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Tunisia</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>May 14, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <last_update_submitted>June 30, 2019</last_update_submitted>
  <last_update_submitted_qc>June 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Monastir</investigator_affiliation>
    <investigator_full_name>Pr. Semir Nouira</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Ketamine-Intranasal-Acute pain-Emergency departement</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</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/NCT03233035
org study id: Ket-Int-Nas-TR
nct id: NCT03233035
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
To evaluate the efficacy and safety of early administration of low-dose intranasal ketamine
      analgesic agents in patients with moderate to severe pain in the ED in reducing the need for
      opioid or non opioids analgesic agents.
Intranasal ketamine for treatment of acute pain in the emergency department : A randomized
      controlled trial

      Introduction :

      Pain is the most common complaint for emergency department (ED) visits [1].The provision of
      adequate, safe, and timely analgesia is a core component of patient care in the emergency
      department (ED). Ketamine is a noncompetitive Nmethyl- D-aspartate and glutamate receptor
      antagonist that decreases central sensitization, "wind-up" phenomena, and pain memory [2,3].

      At subdissociative doses (0.1 to 0.6 mg/kg; most commonly 0.3 mg/kg) maintains potent
      analgesic and amnestic effects that are accompanied by preservation of protective airway
      reflexes, spontaneous respiration, and cardiopulmonary stability [4-6].

      Intranasal route ….

      Objective of the study :

      To evaluate the efficacy and safety of early administration of low-dose intranasal ketamine
      analgesic agents in patients with moderate to severe pain in the ED in reducing the need for
      opioid or class III analgesic agents.

      Materials and Methods :

      Study design :

      It is a ramdomized, prospective, double blind, controlled, multicentric trial. The study is
      registered with clinical.tria.gov (…….).

      Study Setting and Selection of Participants :

      The trial is conducted in three community teaching hospitals :

        -  Emergency department, fattouma bourguiba university hospital, monastir, tunisia

        -  Emergency department, sahloul university hospital, sousse, tunisia

        -  Emergency department, farhat hached university hospital, sousse, tunisia

      ED principal investigators maintain the randomization list, which is generated before the
      start of the study, prepare the medication, and deliver it to the treating physician in a
      blinded manner.

      Inclusion criteria :

      The study includes patients aged 18 to 80 years who presented to the ED with acute limb
      trauma pain with a visual analogue scale (VAS) of 5 or more on a standard 11- point (0 to
      10). An informed consent is necessary.

      Exclusion criteria :

        -  Pregnancy,

        -  Breast-feeding,

        -  Altered mental status,

        -  Allergy to ketamine or morphine or

        -  Weight less than 46 kg or greater than 115 kg,

        -  Unstable vital signs (systolic blood pressure <90 or >180 mm Hg, pulse rate <50 or >150
           beats/min, and respiration rate <10 or >30 breaths/min),

        -  Medical history of acute head or eye injury, seizure, intracranial hypertension, chronic
           pain, severre renal or hepatic insufficiency,

        -  Alcohol or drug abuse,

        -  Psychiatric illness,

        -  Recent (4 hours before) analgesic agent use.

      Protocol :

      In the triage area, each patient having the inclusion criteria receives 25mg of ketamine in
      0.5 ml of serum saline in one pulverisation per nostril or 0.5 mL of normal saline solution
      in one pulverisation per nostril as a placebo according to the predetermined randomization
      list. None of the treating physician or nurses is aware about the medication received. In all
      patients included, the investigators collect vital signs ; demographic and clinical data.

      Study investigators record VAS, and adverse effects at 15, 30, 60, 90, and 120 minutes.

      At 30 minutes, if patients report a pain numeric rating scale score of 5 or greater and
      request additional pain relief, titrated morphine is administered as a rescue analgesic with
      a dose of 0.1 mg/Kg repeated every 3 to 5 minutes if the pain numeric rating scale score is
      still greater or equal to 3.

      All data recorded on data collection sheets, including sex, demographics, medical history,
      and vital signs, were entered into SPSS (version 20.0; IBM Corp) by the research manager.

      Patients's informed consent is obtained. The ethic commitee of our institution approved the
      study.

      Endpoints :

      Primary endpoints :

      - Need for rescue opioids during ED stay

      Secondary endpoints :

        -  requirement of non-opioids analgesic agents.

        -  percentage of patients discharged from the ED with VAS <30.

        -  Safety : adverse events
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Double Blind Study
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Ketamine versus placebo as a double blind study
measure: Number and percentage of patients who need rescue opiods in the two groups
time frame: 30 minutes
description: the need for rescue opioids during ED stay
measure: Intolerance to treatement and adverse events
time frame: 30 minutes and at 120 minutes
description: Noticing any sign of intolerance due to treatement : Dizziness , Vomiting..
measure: Percentage of patients with VAS <30 mm at discharge
time frame: 120 minutes
description: percentage of patients discharged from the ED with VAS <30.
measure: Number and percentage of patients who required non opiods analgesics
time frame: 30 minutes
description: Requirement of non-opioids analgesic agents
arm group label: placebo group
arm group type: Placebo Comparator
description: Intranasal placebo pulverisation
arm group label: Ketamine group
arm group type: Active Comparator
description: Intranasal ketamine pulverisation
intervention type: Drug
intervention name: Ketamine
description: 25mg of ketamine in 0.5 ml of serum saline in one pulverisation per nostril is received
arm group label: Ketamine group
intervention type: Drug
intervention name: Placebo
description: 0.5 mL of normal saline solution as a placebo in one pulverisation per nostril
arm group label: placebo group
other name: normal saline solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Nouira Semir, Professor
role: Principal Investigator
affiliation: university Hospital of Monastir
facility: 
facility: 
country: Tunisia
responsible party type: Principal Investigator
investigator affiliation: University of Monastir
investigator full name: Pr. Semir Nouira
investigator title: Professor
mesh term: Acute Pain
mesh term: Ketamine
sharing ipd: No