<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/NCT03792906</url>
  </required_header>
  <id_info>
    <org_study_id>N71-2018</org_study_id>
    <nct_id>NCT03792906</nct_id>
  </id_info>
  <brief_title>Comparison of Two Norepinephrine Bolus Doses for Management of Post-spinal Hypotension During Cesarean Delivery</brief_title>
  <official_title>Norepinephrine for Management of Post-spinal Anesthesia Hypotension During Cesarean Delivery: a Comparison of Two Bolus Doses</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cairo University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cairo University</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study the investigators will compare two doses of norepinephrine bolus (6 mcg and 10&#xD;
      mcg) in management of maternal hypotensive episode after subarachnoid block during Cesarean&#xD;
      delivery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Maternal hypotension after subarachnoid block is a frequent and deleterious complication&#xD;
      during cesarean delivery. Although prophylaxis against hypotension using vasopressors had&#xD;
      become a standard recommendation; the incidence of hypotension is still ∼ 20% . Thus;&#xD;
      management of maternal hypotension using vasopressor boluses is usually needed .&#xD;
&#xD;
      The commonly used vasopressors during cesarean delivery are ephedrine, phenylephrine, and&#xD;
      recently norepinephrine. The use of ephedrine is usually accompanied with maternal&#xD;
      tachycardia and fetal acidosis. Phenylephrine had been the first line for prevention and&#xD;
      management of maternal hypotension; however, its use might result in bradycardia and&#xD;
      decreased maternal cardiac output .&#xD;
&#xD;
      Norepinephrine is an alpha adrenergic agonist with weak beta adrenergic agonistic activity;&#xD;
      thus, it does not cause significant cardiac depression as phenylephrine does. Norepinephrine&#xD;
      was introduced for use during cesarean delivery with promising results . Few previous studies&#xD;
      investigated the efficacy of Norepinephrine infusion for prevention of maternal hypotension.&#xD;
      A dose-response study had investigated the best dose of Norepinephrine for prevention of&#xD;
      maternal hypotension. In the aforementioned dose-response study, a dose of 6 mcg was reported&#xD;
      as the best dose for prophylaxis against maternal hypotension.&#xD;
&#xD;
      No studies had investigated the best bolus dose of norepinephrine for management of a&#xD;
      maternal hypotensive episode. In this study the investigators will investigate the efficacy&#xD;
      and side effects of two doses of norepinephrine bolus doses (6 mcg and 10 mcg) in management&#xD;
      of maternal hypotensive episode after subarachnoid block during cesarean delivery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 18, 2019</start_date>
  <completion_date type="Actual">May 1, 2019</completion_date>
  <primary_completion_date type="Actual">April 25, 2019</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of successful management of maternal hypotension</measure>
    <time_frame>30 minutes after spinal anesthesia</time_frame>
    <description>number of patients with successful management of maternal hypotensive episode (defined as return of systolic blood pressure to be ≥ 80% of the baseline reading in the next reading 2 minutes after administration of norepinephrine bolus).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of successful management of severe maternal hypotension.</measure>
    <time_frame>30 minutes after spinal anesthesia</time_frame>
    <description>number of patients with successful management of maternal severe hypotensive episode (defined as systolic blood pressure lower than 60% of the baseline reading in the next reading 2 minutes after administration of norepinephrine bolus).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of reactive hypertension</measure>
    <time_frame>30 minutes after spinal anesthesia</time_frame>
    <description>number of patients with reactive hypertension (defined as systolic blood pressure ≥120% from the baseline reading after administration of norepinephrine bolus).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systolic blood pressure.</measure>
    <time_frame>2 hours after subarachnoid block</time_frame>
    <description>Systolic blood pressure measured in mmHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>2 hours after subarachnoid block</time_frame>
    <description>Number of heart beats per minute.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apgar score for evaluation of the activity of the fetus</measure>
    <time_frame>10 minutes</time_frame>
    <description>the Apgar score of the fetus which range from 0 to 10. Th minimum value is 0 and the maximum value is 10. The worst value is 0 and the best value is 10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Umbilical blood acidity</measure>
    <time_frame>10 minutes after delivery</time_frame>
    <description>the measure of acidity or alkalinity of any solution on a logarithmic scale on which 7 is neutral, lower values are more acid and higher values more alkaline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The frequency of vomiting.</measure>
    <time_frame>2 hours after subarachnoid block</time_frame>
    <description>The number of patients with vomiting.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of bradycardia</measure>
    <time_frame>2 hours after subarachnoid block</time_frame>
    <description>number of patients with bradycardia (defined as heart rate less than 55 beat per minute after administration of norepinephrine bolus).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">110</enrollment>
  <condition>Cesarean Section Complications</condition>
  <condition>Spinal Anesthetic Toxicity</condition>
  <arm_group>
    <arm_group_label>Norepinephrine 6 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mothers in this group will receive a bolus of Norepinephrine 6 mcg for management of hypotensive episode after spinal anesthesia using Bupivacaine hydrochloride under prophylactic Norepinephrine infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Norepinephrine 10 mcg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Mothers in this group will receive a bolus of Norepinephrine 10 mcg for management of hypotensive episode after spinal anesthesia using Bupivacaine hydrochloride under prophylactic Norepinephrine infusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Norepinephrine 6 mcg</intervention_name>
    <description>An intravenous bolus of norepinephrine 6 mcg will be administered for management of maternal hypotension.</description>
    <arm_group_label>Norepinephrine 6 mcg</arm_group_label>
    <other_name>Levophed</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Norepinephrine 10 mcg</intervention_name>
    <description>An intravenous bolus of norepinephrine 10 mcg will be administered for management of maternal hypotension.</description>
    <arm_group_label>Norepinephrine 10 mcg</arm_group_label>
    <other_name>Levophed</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Norepinephrine infusion</intervention_name>
    <description>Prophylactic norepinephrine infusion will be started after subarachnoid block.</description>
    <arm_group_label>Norepinephrine 10 mcg</arm_group_label>
    <arm_group_label>Norepinephrine 6 mcg</arm_group_label>
    <other_name>Levophed</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bupivacaine hydrochloride</intervention_name>
    <description>Subarachnoid block will be performed using Bupivacaine hydrochloride (2.2 mL) in addition to fentanyl 25 mcg.</description>
    <arm_group_label>Norepinephrine 10 mcg</arm_group_label>
    <arm_group_label>Norepinephrine 6 mcg</arm_group_label>
    <other_name>marcaine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Scheduled for cesarean delivery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with severe cardiac dysfunction&#xD;
&#xD;
          -  Patients with low blood pressure&#xD;
&#xD;
          -  Patients with ante-partum bleeding&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ahmed M Hasanin, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistant professor of anesthesia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ahmed Mohamed Hasanin</name>
      <address>
        <city>Cairo</city>
        <zip>11432</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 2, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 4, 2019</study_first_posted>
  <last_update_submitted>September 22, 2021</last_update_submitted>
  <last_update_submitted_qc>September 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 24, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cairo University</investigator_affiliation>
    <investigator_full_name>Ahmed Hasanin</investigator_full_name>
    <investigator_title>Assistant professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypotension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Norepinephrine</mesh_term>
    <mesh_term>Bupivacaine</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/NCT03792906
org study id: N71-2018
nct id: NCT03792906
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In this study the investigators will compare two doses of norepinephrine bolus (6 mcg and 10
      mcg) in management of maternal hypotensive episode after subarachnoid block during Cesarean
      delivery.
Maternal hypotension after subarachnoid block is a frequent and deleterious complication
      during cesarean delivery. Although prophylaxis against hypotension using vasopressors had
      become a standard recommendation; the incidence of hypotension is still ∼ 20% . Thus;
      management of maternal hypotension using vasopressor boluses is usually needed .

      The commonly used vasopressors during cesarean delivery are ephedrine, phenylephrine, and
      recently norepinephrine. The use of ephedrine is usually accompanied with maternal
      tachycardia and fetal acidosis. Phenylephrine had been the first line for prevention and
      management of maternal hypotension; however, its use might result in bradycardia and
      decreased maternal cardiac output .

      Norepinephrine is an alpha adrenergic agonist with weak beta adrenergic agonistic activity;
      thus, it does not cause significant cardiac depression as phenylephrine does. Norepinephrine
      was introduced for use during cesarean delivery with promising results . Few previous studies
      investigated the efficacy of Norepinephrine infusion for prevention of maternal hypotension.
      A dose-response study had investigated the best dose of Norepinephrine for prevention of
      maternal hypotension. In the aforementioned dose-response study, a dose of 6 mcg was reported
      as the best dose for prophylaxis against maternal hypotension.

      No studies had investigated the best bolus dose of norepinephrine for management of a
      maternal hypotensive episode. In this study the investigators will investigate the efficacy
      and side effects of two doses of norepinephrine bolus doses (6 mcg and 10 mcg) in management
      of maternal hypotensive episode after subarachnoid block during cesarean delivery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Rate of successful management of maternal hypotension
time frame: 30 minutes after spinal anesthesia
description: number of patients with successful management of maternal hypotensive episode (defined as return of systolic blood pressure to be ≥ 80% of the baseline reading in the next reading 2 minutes after administration of norepinephrine bolus).
measure: Rate of successful management of severe maternal hypotension.
time frame: 30 minutes after spinal anesthesia
description: number of patients with successful management of maternal severe hypotensive episode (defined as systolic blood pressure lower than 60% of the baseline reading in the next reading 2 minutes after administration of norepinephrine bolus).
measure: Incidence of reactive hypertension
time frame: 30 minutes after spinal anesthesia
description: number of patients with reactive hypertension (defined as systolic blood pressure ≥120% from the baseline reading after administration of norepinephrine bolus).
measure: Systolic blood pressure.
time frame: 2 hours after subarachnoid block
description: Systolic blood pressure measured in mmHg.
measure: Heart rate
time frame: 2 hours after subarachnoid block
description: Number of heart beats per minute.
measure: Apgar score for evaluation of the activity of the fetus
time frame: 10 minutes
description: the Apgar score of the fetus which range from 0 to 10. Th minimum value is 0 and the maximum value is 10. The worst value is 0 and the best value is 10.
measure: Umbilical blood acidity
time frame: 10 minutes after delivery
description: the measure of acidity or alkalinity of any solution on a logarithmic scale on which 7 is neutral, lower values are more acid and higher values more alkaline.
measure: The frequency of vomiting.
time frame: 2 hours after subarachnoid block
description: The number of patients with vomiting.
measure: Incidence of bradycardia
time frame: 2 hours after subarachnoid block
description: number of patients with bradycardia (defined as heart rate less than 55 beat per minute after administration of norepinephrine bolus).
arm group label: Norepinephrine 6 mcg
arm group type: Experimental
description: Mothers in this group will receive a bolus of Norepinephrine 6 mcg for management of hypotensive episode after spinal anesthesia using Bupivacaine hydrochloride under prophylactic Norepinephrine infusion
arm group label: Norepinephrine 10 mcg
arm group type: Active Comparator
description: Mothers in this group will receive a bolus of Norepinephrine 10 mcg for management of hypotensive episode after spinal anesthesia using Bupivacaine hydrochloride under prophylactic Norepinephrine infusion.
intervention type: Drug
intervention name: Norepinephrine 6 mcg
description: An intravenous bolus of norepinephrine 6 mcg will be administered for management of maternal hypotension.
arm group label: Norepinephrine 6 mcg
other name: Levophed
intervention type: Drug
intervention name: Norepinephrine 10 mcg
description: An intravenous bolus of norepinephrine 10 mcg will be administered for management of maternal hypotension.
arm group label: Norepinephrine 10 mcg
other name: Levophed
intervention type: Drug
intervention name: Norepinephrine infusion
description: Prophylactic norepinephrine infusion will be started after subarachnoid block.
arm group label: Norepinephrine 10 mcg
arm group label: Norepinephrine 6 mcg
other name: Levophed
intervention type: Drug
intervention name: Bupivacaine hydrochloride
description: Subarachnoid block will be performed using Bupivacaine hydrochloride (2.2 mL) in addition to fentanyl 25 mcg.
arm group label: Norepinephrine 10 mcg
arm group label: Norepinephrine 6 mcg
other name: marcaine
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Ahmed M Hasanin, Professor
role: Principal Investigator
affiliation: Assistant professor of anesthesia
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Cairo University
investigator full name: Ahmed Hasanin
investigator title: Assistant professor
mesh term: Hypotension
mesh term: Norepinephrine
mesh term: Bupivacaine
sharing ipd: No