<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/NCT03302351</url>
  </required_header>
  <id_info>
    <org_study_id>AMMH</org_study_id>
    <nct_id>NCT03302351</nct_id>
  </id_info>
  <brief_title>Dexmedetomidine, Ketamine and Dexmetedomidine-Ketamine Combination for Control of Shivering During Regional Anaethesia</brief_title>
  <official_title>Comparing Dexmedetomidine, Ketamine and Dexmetedomidine-Ketamine Combination to Control Shivering During Regional Anaethesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Shivering is defined as an involuntary, repetitive activity of skeletal muscles. The&#xD;
      incidence of shivering has been found to be quite high, approximately 40-50% in different&#xD;
      studies. It can double or even triple oxygen consumption and carbon dioxide production.&#xD;
      Shivering also increase intraocular and intracranial pressure, and may contribute to&#xD;
      increased wound pain, delayed wound healing, and delayed discharge from post-anaesthetic&#xD;
      care. Apart from being an uncomfortable experience, its deleterious effects deserve primary&#xD;
      prevention and rapid control on occurence.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Shivering is a physiological response to core hypothermia in an attempt to raise the&#xD;
      metabolic heat production. The main causes of intra and postoperative shivering are heat&#xD;
      loss, increased sympathetic tone, pain, and systemic release of pyrogens. Spinal anaesthesia&#xD;
      significantly impairs the thermoregulation system by inhibiting tonic vasoconstriction, which&#xD;
      plays a significant role in temperature regulation. It also causes a redistribution of core&#xD;
      heat from the trunk (below the block level) to the peripheral tissues. These factors&#xD;
      predispose patients to hypothermia and shivering.&#xD;
&#xD;
      The treatment of shivering includes both pharmacological and non-pharmacological methods. The&#xD;
      non-pharmacological management is by external heating like the use of forced air warming,&#xD;
      warming blankets, warmed fluids etc.&#xD;
&#xD;
      According to the results of meta-analysis, the most frequently reported pharmacological&#xD;
      interventions include clonidine, pethidine, tramadol, nefopam, and ketamine. Unfortunately,&#xD;
      no gold standard treatment is known for shivering as the administration of all the available&#xD;
      drugs is associated with various adverse effects.&#xD;
&#xD;
      Dexmedetomidine, a congener of clonidine, is a highly selective adrenoceptor agonist. It has&#xD;
      been used as a sedative agent and is known to reduce the shivering threshold. Few studies&#xD;
      which have explored its anti-shivering potential have inferred that dexmedetomidine is an&#xD;
      effective drug without any major adverse effect and provides good haemodynamic stability.&#xD;
&#xD;
      Ketamine has been tried to prevent shivering during anaesthesia with good results. Ketamine a&#xD;
      competitive NMDA receptor antagonist has a role in thermoregulation at various levels. NMDA&#xD;
      receptor modulates non-adrenergic and serotoninergic neurons in locus coeruleus. It is used&#xD;
      as anti-shivering agent.&#xD;
&#xD;
      Shivering is a physiological response to core hypothermia in an attempt to raise the&#xD;
      metabolic heat production. The main causes of intra and postoperative shivering are heat&#xD;
      loss, increased sympathetic tone, pain, and systemic release of pyrogens. Spinal anaesthesia&#xD;
      significantly impairs the thermoregulation system by inhibiting tonic vasoconstriction, which&#xD;
      plays a significant role in temperature regulation. It also causes a redistribution of core&#xD;
      heat from the trunk (below the block level) to the peripheral tissues. These factors&#xD;
      predispose patients to hypothermia and shivering.&#xD;
&#xD;
      The treatment of shivering includes both pharmacological and non-pharmacological methods. The&#xD;
      non-pharmacological management is by external heating like the use of forced air warming,&#xD;
      warming blankets, warmed fluids etc.&#xD;
&#xD;
      According to the results of meta-analysis, the most frequently reported pharmacological&#xD;
      interventions include clonidine, pethidine, tramadol, nefopam, and ketamine. Unfortunately,&#xD;
      no gold standard treatment is known for shivering as the administration of all the available&#xD;
      drugs is associated with various adverse effects.&#xD;
&#xD;
      Dexmedetomidine, a congener of clonidine, is a highly selective adrenoceptor agonist. It has&#xD;
      been used as a sedative agent and is known to reduce the shivering threshold. Few studies&#xD;
      which have explored its anti-shivering potential have inferred that dexmedetomidine is an&#xD;
      effective drug without any major adverse effect and provides good haemodynamic stability.&#xD;
&#xD;
      Ketamine has been tried to prevent shivering during anaesthesia with good results. Ketamine a&#xD;
      competitive NMDA receptor antagonist has a role in thermoregulation at various levels. NMDA&#xD;
      receptor modulates non-adrenergic and serotoninergic neurons in locus coeruleus. It is used&#xD;
      as anti-shivering agent.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Actual">April 1, 2018</completion_date>
  <primary_completion_date type="Actual">March 1, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>shivering score</measure>
    <time_frame>10 minutes</time_frame>
    <description>p1(frequency of number)</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">94</enrollment>
  <condition>Shivering</condition>
  <arm_group>
    <arm_group_label>Dexmedetomidine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1st group will include 30 patients will receive intravenous dexmedetomidine 1 mcg/kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ketamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2nd group will include 31 patients will receive intravenous ketamine 0.4 mg/kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dexmetedomidine-Ketamine combination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3rd group will include 33 patients will receive combination between intravenous dexmedetomidine 0.5mcg/kg and low dose ketamine 0.25mg/kg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexmedetomidine</intervention_name>
    <description>30 patients will receive intravenous dexmedetomidine 1 mcg/kg.</description>
    <arm_group_label>Dexmedetomidine</arm_group_label>
    <other_name>precedex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ketamine</intervention_name>
    <description>31 patients will receive intravenous ketamine 0.4 mg/kg.</description>
    <arm_group_label>Ketamine</arm_group_label>
    <other_name>katalar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexmetedomidine+Ketamine</intervention_name>
    <description>33 patients will receive combination between intravenous dexmedetomidine 0.5mcg/kg + low dose ketamine 0.25mg/kg.</description>
    <arm_group_label>Dexmetedomidine-Ketamine combination</arm_group_label>
    <other_name>precedex+katalar</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  This study will include adults between 18 and 60 years of age undergo elective lower&#xD;
             abdominal and lower limb surgery using spinal anaesthesia.&#xD;
&#xD;
          -  ASA grade I - II&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient refusal.&#xD;
&#xD;
          -  Patients who have temperature over 37.3 or below 36 celsius degree.&#xD;
&#xD;
          -  Known allergies to the study drugs.&#xD;
&#xD;
          -  Contraindication to spinal anaesthesia as coagulopathy,&#xD;
&#xD;
          -  patients with thyroid disease, Parkinson disease, dysautonomia, Raynaud syndrome, use&#xD;
             of sedative-hypnotic agent or vasodilators.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Ghada Mohammmad Aboalfadl</name>
      <address>
        <city>Assiut</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Nikolic K, Popovic R. Conductometric determination of periciazine. Acta Pol Pharm. 1978;35(2):195-9. No abstract available.</citation>
    <PMID>27062</PMID>
  </reference>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 26, 2017</study_first_submitted>
  <study_first_submitted_qc>September 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 5, 2017</study_first_posted>
  <last_update_submitted>July 1, 2018</last_update_submitted>
  <last_update_submitted_qc>July 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Ghada Mohammed AboelFadl</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexmedetomidine</mesh_term>
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03302351
org study id: AMMH
nct id: NCT03302351
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Shivering is defined as an involuntary, repetitive activity of skeletal muscles. The
      incidence of shivering has been found to be quite high, approximately 40-50% in different
      studies. It can double or even triple oxygen consumption and carbon dioxide production.
      Shivering also increase intraocular and intracranial pressure, and may contribute to
      increased wound pain, delayed wound healing, and delayed discharge from post-anaesthetic
      care. Apart from being an uncomfortable experience, its deleterious effects deserve primary
      prevention and rapid control on occurence.
Shivering is a physiological response to core hypothermia in an attempt to raise the
      metabolic heat production. The main causes of intra and postoperative shivering are heat
      loss, increased sympathetic tone, pain, and systemic release of pyrogens. Spinal anaesthesia
      significantly impairs the thermoregulation system by inhibiting tonic vasoconstriction, which
      plays a significant role in temperature regulation. It also causes a redistribution of core
      heat from the trunk (below the block level) to the peripheral tissues. These factors
      predispose patients to hypothermia and shivering.

      The treatment of shivering includes both pharmacological and non-pharmacological methods. The
      non-pharmacological management is by external heating like the use of forced air warming,
      warming blankets, warmed fluids etc.

      According to the results of meta-analysis, the most frequently reported pharmacological
      interventions include clonidine, pethidine, tramadol, nefopam, and ketamine. Unfortunately,
      no gold standard treatment is known for shivering as the administration of all the available
      drugs is associated with various adverse effects.

      Dexmedetomidine, a congener of clonidine, is a highly selective adrenoceptor agonist. It has
      been used as a sedative agent and is known to reduce the shivering threshold. Few studies
      which have explored its anti-shivering potential have inferred that dexmedetomidine is an
      effective drug without any major adverse effect and provides good haemodynamic stability.

      Ketamine has been tried to prevent shivering during anaesthesia with good results. Ketamine a
      competitive NMDA receptor antagonist has a role in thermoregulation at various levels. NMDA
      receptor modulates non-adrenergic and serotoninergic neurons in locus coeruleus. It is used
      as anti-shivering agent.

      Shivering is a physiological response to core hypothermia in an attempt to raise the
      metabolic heat production. The main causes of intra and postoperative shivering are heat
      loss, increased sympathetic tone, pain, and systemic release of pyrogens. Spinal anaesthesia
      significantly impairs the thermoregulation system by inhibiting tonic vasoconstriction, which
      plays a significant role in temperature regulation. It also causes a redistribution of core
      heat from the trunk (below the block level) to the peripheral tissues. These factors
      predispose patients to hypothermia and shivering.

      The treatment of shivering includes both pharmacological and non-pharmacological methods. The
      non-pharmacological management is by external heating like the use of forced air warming,
      warming blankets, warmed fluids etc.

      According to the results of meta-analysis, the most frequently reported pharmacological
      interventions include clonidine, pethidine, tramadol, nefopam, and ketamine. Unfortunately,
      no gold standard treatment is known for shivering as the administration of all the available
      drugs is associated with various adverse effects.

      Dexmedetomidine, a congener of clonidine, is a highly selective adrenoceptor agonist. It has
      been used as a sedative agent and is known to reduce the shivering threshold. Few studies
      which have explored its anti-shivering potential have inferred that dexmedetomidine is an
      effective drug without any major adverse effect and provides good haemodynamic stability.

      Ketamine has been tried to prevent shivering during anaesthesia with good results. Ketamine a
      competitive NMDA receptor antagonist has a role in thermoregulation at various levels. NMDA
      receptor modulates non-adrenergic and serotoninergic neurons in locus coeruleus. It is used
      as anti-shivering agent.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: shivering score
time frame: 10 minutes
description: p1(frequency of number)
arm group label: Dexmedetomidine
arm group type: Experimental
description: 1st group will include 30 patients will receive intravenous dexmedetomidine 1 mcg/kg.
arm group label: Ketamine
arm group type: Experimental
description: 2nd group will include 31 patients will receive intravenous ketamine 0.4 mg/kg.
arm group label: Dexmetedomidine-Ketamine combination
arm group type: Experimental
description: 3rd group will include 33 patients will receive combination between intravenous dexmedetomidine 0.5mcg/kg and low dose ketamine 0.25mg/kg.
intervention type: Drug
intervention name: Dexmedetomidine
description: 30 patients will receive intravenous dexmedetomidine 1 mcg/kg.
arm group label: Dexmedetomidine
other name: precedex
intervention type: Drug
intervention name: ketamine
description: 31 patients will receive intravenous ketamine 0.4 mg/kg.
arm group label: Ketamine
other name: katalar
intervention type: Drug
intervention name: Dexmetedomidine+Ketamine
description: 33 patients will receive combination between intravenous dexmedetomidine 0.5mcg/kg + low dose ketamine 0.25mg/kg.
arm group label: Dexmetedomidine-Ketamine combination
other name: precedex+katalar
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
facility: 
country: Egypt
citation: Nikolic K, Popovic R. Conductometric determination of periciazine. Acta Pol Pharm. 1978;35(2):195-9. No abstract available.
PMID: 27062
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Ghada Mohammed AboelFadl
investigator title: Principal Investigator
mesh term: Dexmedetomidine
mesh term: Ketamine