<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/NCT04403724</url>
  </required_header>
  <id_info>
    <org_study_id>17300377 (sequential)</org_study_id>
    <nct_id>NCT04403724</nct_id>
  </id_info>
  <brief_title>Sequential and Mixture Injection of Opioids and Hyperbaric Bupivacaine</brief_title>
  <official_title>Comparison of Sequential and Mixture Injection of Opioids and Hyperbaric Bupivacaine for Subarachnoid Block for Elective Caesarean Section; a Randomised Controlled Study</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>
      Neuraxial anesthesia, especially the subarachnoid block, is the preferred method for LSCS.&#xD;
      The intrathecal spread of local anesthetic drugs is unpredictable. However, Baricity, which&#xD;
      is the relative density of local anesthetics to that of CSF, is a key determinant of the&#xD;
      local anesthetic spread within the subarachnoid space. Alterations in the baricity of a&#xD;
      solution to the extent of 0.0006 g/ml-1 can alter the spread of local anesthetic solution in&#xD;
      CSF. Patients features such as position, weight, height, and age, and local anaesthetic&#xD;
      characteristics such as density, PH, and temperature may play a role as well.&#xD;
&#xD;
      Bupivacaine is the main local anaesthetic used frequently for the subarachnoid block.&#xD;
      Hyperbaric bupivacaine has dextrose added at a concentration of 80 g/ml to increase its&#xD;
      density to 1.0262 which is higher than that of cerebrospinal fluid (CSF), leading to a more&#xD;
      predictable spread after intrathecal injection.&#xD;
&#xD;
      Opioids such as morphine and fentanyl are commonly injected as adjuvants to hyperbaric&#xD;
      bupivacaine. Their synergistic role leads to satisfactory block at smaller subtherapeutic&#xD;
      doses of bupivacaine which minimizes the associated side effects. The combination of fentanyl&#xD;
      which is lipophilic opioid and morphine which is hydrophilic opioid results in rapid onset&#xD;
      and prolonged course of perioperative analgesia. In an in vitro study, the mean densities of&#xD;
      fentanyl and morphine were found to be 0.9957 and 1.0013 respectively while the mean density&#xD;
      of CSF in term pregnant woman is 1.000306. Thus, opioids spread freely within the CSF&#xD;
      interacting on the spinal and supraspinal opioid receptors. They have a synergistic effect to&#xD;
      bupivacaine leading to adequate sensory blockade with lesser hemodynamic adverse effects.&#xD;
&#xD;
      Nevertheless, opioids are commonly mixed with hyperbaric bupivacaine in a single syringe&#xD;
      before intrathecal injection. This practice alters the density and PH of the mixture which&#xD;
      may impact the pharmacokinetics of each individual drug. Therefore, we hypothesize in this&#xD;
      study that separate injection of opioids and hyperbaric bupivacaine may improve their&#xD;
      intrathecal spread. This will not only improve the quality of anesthesia, but it will also&#xD;
      decrease the associated hemodynamic adverse events and the incidence of undesired high&#xD;
      sensory block levels, which all will increase the perioperative patient satisfaction.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 11, 2020</start_date>
  <completion_date type="Actual">March 17, 2021</completion_date>
  <primary_completion_date type="Actual">March 17, 2021</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, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>duration to the maximal sensory block to light touch</measure>
    <time_frame>intraoperative</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">126</enrollment>
  <condition>Bupivacaine Adverse Reaction</condition>
  <condition>Regional Anesthesia Morbidity</condition>
  <condition>Cesarean Section Complications</condition>
  <arm_group>
    <arm_group_label>premixed injection</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>will receive an intrathecal injection of 2.4 ml hyperbaric bupivacaine 0.5%, 20 µg fentanyl, and 100 µg preservative-free morphine mixed together.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sequential injections</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>will receive an intrathecal injection of 2,4 ml hyperbaric bupivacaine 0.5% followed immediately by the opioid mixture by two separate syringes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bupivacaine-fentanyl-Morphine.</intervention_name>
    <description>2.4 ml Bupivacaine 0.5%, 20 µg Fentanyl and, 100 µg preservative free morphine</description>
    <arm_group_label>premixed injection</arm_group_label>
    <arm_group_label>sequential injections</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  LSCS&#xD;
&#xD;
          -  ASA I or II&#xD;
&#xD;
          -  Single baby pregnancy of more than 32 weeks&#xD;
&#xD;
          -  Elective or semi-elective surgery (category 3 and 4 Caesarean sections)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Abnormal Placentation&#xD;
&#xD;
          -  PET&#xD;
&#xD;
          -  Disordered coagulation&#xD;
&#xD;
          -  Allergy to opioids or local anesthetic.&#xD;
&#xD;
          -  BMI &gt; 35&#xD;
&#xD;
          -  Spine surgery&#xD;
&#xD;
          -  Cardiac disease&#xD;
&#xD;
          -  Extremes of height; height more than 180 or less than 140&#xD;
&#xD;
          -  Multiple pregnancy or polyhydramnios&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Assiut University hospital</name>
      <address>
        <city>Assiut</city>
        <zip>11111</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>April 16, 2021</last_update_submitted>
  <last_update_submitted_qc>April 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Mostafa Samy Abbas</investigator_full_name>
    <investigator_title>associate professor of anesthesia</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Bupivacaine</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/NCT04403724
org study id: 17300377 (sequential)
nct id: NCT04403724
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Neuraxial anesthesia, especially the subarachnoid block, is the preferred method for LSCS.
      The intrathecal spread of local anesthetic drugs is unpredictable. However, Baricity, which
      is the relative density of local anesthetics to that of CSF, is a key determinant of the
      local anesthetic spread within the subarachnoid space. Alterations in the baricity of a
      solution to the extent of 0.0006 g/ml-1 can alter the spread of local anesthetic solution in
      CSF. Patients features such as position, weight, height, and age, and local anaesthetic
      characteristics such as density, PH, and temperature may play a role as well.

      Bupivacaine is the main local anaesthetic used frequently for the subarachnoid block.
      Hyperbaric bupivacaine has dextrose added at a concentration of 80 g/ml to increase its
      density to 1.0262 which is higher than that of cerebrospinal fluid (CSF), leading to a more
      predictable spread after intrathecal injection.

      Opioids such as morphine and fentanyl are commonly injected as adjuvants to hyperbaric
      bupivacaine. Their synergistic role leads to satisfactory block at smaller subtherapeutic
      doses of bupivacaine which minimizes the associated side effects. The combination of fentanyl
      which is lipophilic opioid and morphine which is hydrophilic opioid results in rapid onset
      and prolonged course of perioperative analgesia. In an in vitro study, the mean densities of
      fentanyl and morphine were found to be 0.9957 and 1.0013 respectively while the mean density
      of CSF in term pregnant woman is 1.000306. Thus, opioids spread freely within the CSF
      interacting on the spinal and supraspinal opioid receptors. They have a synergistic effect to
      bupivacaine leading to adequate sensory blockade with lesser hemodynamic adverse effects.

      Nevertheless, opioids are commonly mixed with hyperbaric bupivacaine in a single syringe
      before intrathecal injection. This practice alters the density and PH of the mixture which
      may impact the pharmacokinetics of each individual drug. Therefore, we hypothesize in this
      study that separate injection of opioids and hyperbaric bupivacaine may improve their
      intrathecal spread. This will not only improve the quality of anesthesia, but it will also
      decrease the associated hemodynamic adverse events and the incidence of undesired high
      sensory block levels, which all will increase the perioperative patient satisfaction.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: duration to the maximal sensory block to light touch
time frame: intraoperative
arm group label: premixed injection
arm group type: Active Comparator
description: will receive an intrathecal injection of 2.4 ml hyperbaric bupivacaine 0.5%, 20 µg fentanyl, and 100 µg preservative-free morphine mixed together.
arm group label: sequential injections
arm group type: Active Comparator
description: will receive an intrathecal injection of 2,4 ml hyperbaric bupivacaine 0.5% followed immediately by the opioid mixture by two separate syringes.
intervention type: Drug
intervention name: Bupivacaine-fentanyl-Morphine.
description: 2.4 ml Bupivacaine 0.5%, 20 µg Fentanyl and, 100 µg preservative free morphine
arm group label: premixed injection
arm group label: sequential injections
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Mostafa Samy Abbas
investigator title: associate professor of anesthesia
mesh term: Fentanyl
mesh term: Morphine
mesh term: Bupivacaine