<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/NCT03230474</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00009914</org_study_id>
    <nct_id>NCT03230474</nct_id>
  </id_info>
  <brief_title>a Small Dose of Naloxone,Minimize Intrathecal Morphine Side Effects</brief_title>
  <official_title>Ultra Small Dose of Intrathecal Naloxone to Minimize Morphine Induced Side- Effects in Patients Undergoing Minor Anal Surgery Under Spinal Anesthesia. A Randomized Double Blind Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      I.V naloxone decreases incidence and severity of the common morphine side effects (pruritis,&#xD;
      nausea/emesis, constipation, urinary retention, respiratory depression and undesirable&#xD;
      sedation) so using it as additive to intrathecal morphine in patients undergoing anal&#xD;
      surgeries under spinal anesthesia may be beneficail&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Bupivacaine hydrochloride is a commonly used local anesthetic in spinal anesthesia, however,&#xD;
      the duration of spinal analgesia by bupivacaine is limited to about 75-150 minutes,&#xD;
      therefore, various additives have been used along with bupivacaine for the prolongation of&#xD;
      its effect, to improve the quality of analgesia, and to minimize the requirement for&#xD;
      postoperative analgesics .&#xD;
&#xD;
      Opioids may be added to local anesthetic solutions to enhance surgical anesthesia and provide&#xD;
      postoperative analgesia . This effect is mediated at the dorsal horn of the spinal cord,&#xD;
      where opioids mimic the effect of endogenous enkephalins. The use of intrathecal (IT)&#xD;
      morphine (0.1 to 0.5 mg) can provide effective control of postoperative pain for roughly 24&#xD;
      hours . However, the use of IT morphine may result in serious side effects e.g. pruritus 53%,&#xD;
      nausea and vomiting 43%.urinary retention 43% and delayed respiratory depression . These side&#xD;
      effects may lead to patient discomfort and prolonged hospital stay thus limiting the&#xD;
      usefulness of IT morphine.&#xD;
&#xD;
      Naloxone has an extremely high affinity for μ-opioid receptors in the central nervous system&#xD;
      (CNS). Naloxone is a μ-opioid receptor (MOR) competitive antagonist, and its rapid blockade&#xD;
      of those receptors often produces rapid onset of withdrawal symptoms. Naloxone also has an&#xD;
      antagonist action, though with a lower affinity, at κ- (KOR) and δ-opioid receptors (DOR).&#xD;
      Unlike other opioid receptor antagonists, naloxone is essentially a pure antagonist with no&#xD;
      agonist properties.&#xD;
&#xD;
      I.V naloxone decreases incidence and severity of the common morphine side effects (pruritis,&#xD;
      nausea/emesis, constipation, urinary retention, respiratory depression and undesirable&#xD;
      sedation) The addition of naloxone to morphine decreases the opioid related side effects&#xD;
      without affection of postoperative analgesia. This combination can be used for the treatment&#xD;
      of severe refractory chronic low back pain.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2016</start_date>
  <completion_date type="Actual">April 2017</completion_date>
  <primary_completion_date type="Actual">February 2017</primary_completion_date>
  <phase>N/A</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, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>post operative vomiting</measure>
    <time_frame>24 hours</time_frame>
    <description>vomiting and nausea incidence</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>pain</measure>
    <time_frame>24 hour postoperatively</time_frame>
    <description>will be measured by VAS</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Post-Op Complication</condition>
  <arm_group>
    <arm_group_label>group 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>50 patients of this group will receive 5 mg of 0.5% hyperbaric bupivacaine with 0.2 mg morphine in 0.5 ml volume plus 0.5 ml as placebo (total volume 2 mL)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>group 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>50 patients of this group will receive 5 mg of 0.5% hyperbaric bupivacaine with 0.2 mg morphine in 0.5 ml volume plus 5ng\ kg naloxone in 0.5 ml volume (total volume 2mL).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <description>50 patients of this group will receive 5 mg of 0.5% hyperbaric bupivacaine with 0.2 mg morphine in 0.5 ml volume plus 0.5 ml as placebo (total volume 2 mL)</description>
    <arm_group_label>group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine-Naloxone</intervention_name>
    <description>50 patients of this group will receive 5 mg of 0.5% hyperbaric bupivacaine with 0.2 mg morphine in 0.5 ml volume plus 5ng\ kg naloxone in 0.5 ml volume (total volume 2mL).</description>
    <arm_group_label>group 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ASA physical status I - II&#xD;
&#xD;
          -  undergoing anal surgery with spinal anesthesia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Renal ,hepatic and cardiac patients -Infection at the site of injection.-&#xD;
&#xD;
          -  Coagulopathy or other bleeding diathesis. -Preexisting neurologic deficits.-&#xD;
&#xD;
          -  History of hypersensitivity to any of the given the drugs.&#xD;
&#xD;
          -  Inability to communicate with the investigator and the hospital staff.&#xD;
&#xD;
          -  History of chronic opioid use.&#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>Emad Zarief Kamel Said</name>
      <address>
        <city>Assiut</city>
        <zip>71111</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>July 23, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>October 2, 2017</last_update_submitted>
  <last_update_submitted_qc>October 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Emad Zarief , MD</investigator_full_name>
    <investigator_title>Lecturer of anesthesia and ICU</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Postoperative Complications</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Naloxone</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/NCT03230474
org study id: IRB00009914
nct id: NCT03230474
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
I.V naloxone decreases incidence and severity of the common morphine side effects (pruritis,
      nausea/emesis, constipation, urinary retention, respiratory depression and undesirable
      sedation) so using it as additive to intrathecal morphine in patients undergoing anal
      surgeries under spinal anesthesia may be beneficail
Bupivacaine hydrochloride is a commonly used local anesthetic in spinal anesthesia, however,
      the duration of spinal analgesia by bupivacaine is limited to about 75-150 minutes,
      therefore, various additives have been used along with bupivacaine for the prolongation of
      its effect, to improve the quality of analgesia, and to minimize the requirement for
      postoperative analgesics .

      Opioids may be added to local anesthetic solutions to enhance surgical anesthesia and provide
      postoperative analgesia . This effect is mediated at the dorsal horn of the spinal cord,
      where opioids mimic the effect of endogenous enkephalins. The use of intrathecal (IT)
      morphine (0.1 to 0.5 mg) can provide effective control of postoperative pain for roughly 24
      hours . However, the use of IT morphine may result in serious side effects e.g. pruritus 53%,
      nausea and vomiting 43%.urinary retention 43% and delayed respiratory depression . These side
      effects may lead to patient discomfort and prolonged hospital stay thus limiting the
      usefulness of IT morphine.

      Naloxone has an extremely high affinity for μ-opioid receptors in the central nervous system
      (CNS). Naloxone is a μ-opioid receptor (MOR) competitive antagonist, and its rapid blockade
      of those receptors often produces rapid onset of withdrawal symptoms. Naloxone also has an
      antagonist action, though with a lower affinity, at κ- (KOR) and δ-opioid receptors (DOR).
      Unlike other opioid receptor antagonists, naloxone is essentially a pure antagonist with no
      agonist properties.

      I.V naloxone decreases incidence and severity of the common morphine side effects (pruritis,
      nausea/emesis, constipation, urinary retention, respiratory depression and undesirable
      sedation) The addition of naloxone to morphine decreases the opioid related side effects
      without affection of postoperative analgesia. This combination can be used for the treatment
      of severe refractory chronic low back pain.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: post operative vomiting
time frame: 24 hours
description: vomiting and nausea incidence
measure: pain
time frame: 24 hour postoperatively
description: will be measured by VAS
arm group label: group 1
arm group type: Active Comparator
description: 50 patients of this group will receive 5 mg of 0.5% hyperbaric bupivacaine with 0.2 mg morphine in 0.5 ml volume plus 0.5 ml as placebo (total volume 2 mL)
arm group label: group 2
arm group type: Active Comparator
description: 50 patients of this group will receive 5 mg of 0.5% hyperbaric bupivacaine with 0.2 mg morphine in 0.5 ml volume plus 5ng\ kg naloxone in 0.5 ml volume (total volume 2mL).
intervention type: Drug
intervention name: Morphine
description: 50 patients of this group will receive 5 mg of 0.5% hyperbaric bupivacaine with 0.2 mg morphine in 0.5 ml volume plus 0.5 ml as placebo (total volume 2 mL)
arm group label: group 1
intervention type: Drug
intervention name: Morphine-Naloxone
description: 50 patients of this group will receive 5 mg of 0.5% hyperbaric bupivacaine with 0.2 mg morphine in 0.5 ml volume plus 5ng\ kg naloxone in 0.5 ml volume (total volume 2mL).
arm group label: group 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Emad Zarief , MD
investigator title: Lecturer of anesthesia and ICU
mesh term: Postoperative Complications
mesh term: Morphine
mesh term: Naloxone