<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/NCT03282669</url>
  </required_header>
  <id_info>
    <org_study_id>STU00203985</org_study_id>
    <nct_id>NCT03282669</nct_id>
  </id_info>
  <brief_title>TC02 Obese Women Using It Morphine vs PCA IV Hydromorphone for Post-Cesarean Analgesia</brief_title>
  <official_title>Randomized Controlled Trial Evaluating the Transcutaneous Carbon Dioxide Measurements in Obese Women Using Intrathecal Morphine Versus Patient-Controlled Intravenous Hydromorphone for Post-Cesarean Analgesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northwestern University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Northwestern University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cesarean deliveries are the most commonly performed surgery in the United States and account&#xD;
      for 32.9% of all births.8,9 The ASA recommends the use of neuraxial opioids of post-cesarean&#xD;
      analgesia partly because respiratory depression in the obstetric population, as measured by&#xD;
      intermittent respiratory rate and pulse oximetry, is reported to be low (0-1.2%).10,11&#xD;
      Respiratory depression lacks a standard definition,12 but the most sensitive means of&#xD;
      detecting respiratory depression is hypercapnia.1,3 Two recent studies using continuous&#xD;
      hypercapnia (&gt;50mmHg PaCO2) monitoring demonstrated higher rates of respiratory depression&#xD;
      (17.8-37%) in healthy, non-obese women receiving intrathecal opioids for post-cesarean&#xD;
      analgesia.13,14 In addition, supplemental opioids are required in the majority of women&#xD;
      receiving intrathecal morphine and may increase the risk of respiratory depression.11,14&#xD;
      Anesthesiologists debate whether neuraxial opioids or intravenous patient controlled opioid&#xD;
      analgesia (PCA) are the safest practice for postoperative analgesia in obese parturients&#xD;
      following cesarean delivery. The ASA recommendations to employ neuraxial analgesia&#xD;
      post-cesarean delivery does not differentiate between non-obese and obese women who now make&#xD;
      up 30.3% in US women of child-bearing age.2 Obesity has been described as a risk factor for&#xD;
      respiratory depression in those receiving opioids via any route of opioid&#xD;
      administration,11,15, 17 but whether obesity itself is the risk factor or associated&#xD;
      co-morbidities such as sleep apnea is debated.&#xD;
&#xD;
      Studies are conflicting whether intrathecal opioids or patient controlled intravenous opioids&#xD;
      cause more respiratory depression. Several studies have documented the incidence of&#xD;
      respiratory depression with IV PCA; the rates range from 0.19% to 5.2%, which are equivalent&#xD;
      or higher than those reported for intrathecal opioids. (Hagle 16). Dalchow et al.&#xD;
      demonstrated higher rates of hypercapnia in patients receiving intrathecal opioid compared&#xD;
      with those receiving intravenous opioid via patient controlled analgesia in nonobese women&#xD;
      following cesarean delivery. (Dalchow)&#xD;
&#xD;
      The Topological Oscillation Search with Kinematical Analysis (TOSCA) monitor allows a&#xD;
      noninvasive method to measure transcutaneous carbon dioxide levels, with relative accuracy&#xD;
      compared to arterial carbon dioxide monitoring.4-7 No studies have examined transcutaneous&#xD;
      carbon dioxide levels in obese women following cesarean delivery using any form of&#xD;
      postoperative analgesia. The investigators propose a randomized controlled trial using&#xD;
      continuous transcutaneous carbon dioxide monitoring to evaluate the degree of respiratory&#xD;
      depression in obese women receiving neuraxial opioid compared to intravenous opioid via PCA&#xD;
      for post-cesarean analgesia.&#xD;
&#xD;
      Two studies have demonstrated high rates of hypercapnia in non-obese women following&#xD;
      administration of intrathecal morphine for cesarean delivery in the postpartum period.&#xD;
      (Dalchow, Bauchat) Dalchow et al. demonstrated higher rates of hypercapnia in women receiving&#xD;
      intrathecal diamorphine than intravenous morphine delivered via patient controlled analgesia.&#xD;
      It is unclear whether intrathecal morphine causes more or less respiratory depression than&#xD;
      intravenous opioid delivered via patient-controlled analgesia in obese women.&#xD;
&#xD;
      This study will add to the understanding of respiratory function in the immediate postpartum&#xD;
      period in obese women using opioids via intrathecal or intravenous routes. This study will&#xD;
      better inform guidelines for the postpartum analgesic route of choice in the obese obstetric&#xD;
      population and allow the investigators to make recommendations for the detection and&#xD;
      prevention of respiratory depression after opioid administration in the obstetric population.&#xD;
&#xD;
      Objective is to examine the transcutaneous carbon dioxide levels in obese women using either&#xD;
      intrathecal morphine or intravenous patient-controlled hydromorphone for post-cesarean&#xD;
      analgesia.&#xD;
&#xD;
      The hypothesis is carbon dioxide levels will be significantly higher in obese women receiving&#xD;
      intrathecal morphine versus obese women receiving intravenous patient controlled intravenous&#xD;
      hydromorphone.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Change in institutional policy. Change in resources available.&#xD;
  </why_stopped>
  <start_date type="Anticipated">August 2019</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of hypercapnia</measure>
    <time_frame>24 hours post delivery</time_frame>
    <description>Incidence of hypercapnia (transcutaneous CO2 levels &gt;50mmHg) in the intrathecal morphine versus patient controlled intravenous morphine groups</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Opioid consumption</measure>
    <time_frame>24 hours post delivery</time_frame>
    <description>Amount of opioids used during the time from delivery to 24 hours post delivery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NSAID consumption</measure>
    <time_frame>24 hours post delivery</time_frame>
    <description>Amount of NSAID's used during the time from delivery to 24 hours post delivery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory rate</measure>
    <time_frame>24 hours post delivery</time_frame>
    <description>Hourly respiratory rates for the first 12 hours then every 2 hours for the next 12 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sedation scores</measure>
    <time_frame>delivery to 12 hours post delivery</time_frame>
    <description>Sedation scores as scored on the Richmond Agitation and Sedation Scale at 2 hours, 6 hour and 12 hours post delivery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Scores</measure>
    <time_frame>24 hours</time_frame>
    <description>Pain scores on a scale of 0 (low)-10 (high) will be documented every hour for the first 24 hours after delivery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulse oximetry</measure>
    <time_frame>24 hours post delivery</time_frame>
    <description>Pulse oximetry will be collected using the transcutaneous Co2 monitor for 24 hours after deliuvery.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Pain, Postoperative</condition>
  <condition>Obesity</condition>
  <condition>Respiratory Insufficiency</condition>
  <arm_group>
    <arm_group_label>Intrathecal Morphine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Administration of 100µg intrathecal morphine to be given in the operative area.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intravenous Hydromorphone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Administration of intravenous hydromorphone give IV pca in the post operative area.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intrathecal Morphine</intervention_name>
    <description>Intrathecal Morphine administered in the operating room.</description>
    <arm_group_label>Intrathecal Morphine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravenous hydromorphone</intervention_name>
    <description>Intravenous hydromorphone administered via IV in the post operative area.</description>
    <arm_group_label>Intravenous Hydromorphone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Term (≥37 week's gestation)&#xD;
&#xD;
          -  Healthy&#xD;
&#xD;
          -  ASA class 2-3&#xD;
&#xD;
          -  BMI ≥40kg/m2 scheduled for elective cesarean section whose anesthetic plan is for&#xD;
             neuraxial anesthesia (spinal or combined-spinal epidural technique)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women with ASA &gt;3,&#xD;
&#xD;
          -  BMI &lt;40 kg/m2&#xD;
&#xD;
          -  Allergy to any of the medications used for pain control&#xD;
&#xD;
          -  Contraindication to the spinal anesthetic technique&#xD;
&#xD;
          -  Known sleep apnea or other sleep disordered breathing&#xD;
&#xD;
          -  Regular use of other medications that cause respiratory depression (ie.&#xD;
             benzodiazepines).&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Feyce Peralta, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <results_reference>
    <citation>Lee LA, Caplan RA, Stephens LS, Posner KL, Terman GW, Voepel-Lewis T, Domino KB. Postoperative opioid-induced respiratory depression: a closed claims analysis. Anesthesiology. 2015 Mar;122(3):659-65. doi: 10.1097/ALN.0000000000000564.</citation>
    <PMID>25536092</PMID>
  </results_reference>
  <results_reference>
    <citation>Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014 Feb 26;311(8):806-14. doi: 10.1001/jama.2014.732.</citation>
    <PMID>24570244</PMID>
  </results_reference>
  <results_reference>
    <citation>Practice Guidelines for the Prevention, Detection, and Management of Respiratory Depression Associated with Neuraxial Opioid Administration: An Updated Report by the American Society of Anesthesiologists Task Force on Neuraxial Opioids and the American Society of Regional Anesthesia and Pain Medicine. Anesthesiology. 2016 Mar;124(3):535-52. doi: 10.1097/ALN.0000000000000975. No abstract available.</citation>
    <PMID>26655725</PMID>
  </results_reference>
  <results_reference>
    <citation>McCormack JG, Kelly KP, Wedgwood J, Lyon R. The effects of different analgesic regimens on transcutaneous CO2 after major surgery. Anaesthesia. 2008 Aug;63(8):814-21. doi: 10.1111/j.1365-2044.2008.05487.x.</citation>
    <PMID>18699897</PMID>
  </results_reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>May 5, 2022</last_update_submitted>
  <last_update_submitted_qc>May 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Northwestern University</investigator_affiliation>
    <investigator_full_name>Feyce M. Peralta, MD, MS</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Pregnancy</keyword>
  <keyword>Transcutaneous Carbon Dioxide Monitoring</keyword>
  <keyword>Pulse Oximetry</keyword>
  <keyword>Cesarean Section</keyword>
  <keyword>Postoperative pain control</keyword>
  <keyword>High BMI</keyword>
  <keyword>Hypercarbia</keyword>
  <keyword>Hypoxemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Hydromorphone</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/NCT03282669
org study id: STU00203985
nct id: NCT03282669
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Cesarean deliveries are the most commonly performed surgery in the United States and account
      for 32.9% of all births.8,9 The ASA recommends the use of neuraxial opioids of post-cesarean
      analgesia partly because respiratory depression in the obstetric population, as measured by
      intermittent respiratory rate and pulse oximetry, is reported to be low (0-1.2%).10,11
      Respiratory depression lacks a standard definition,12 but the most sensitive means of
      detecting respiratory depression is hypercapnia.1,3 Two recent studies using continuous
      hypercapnia (>50mmHg PaCO2) monitoring demonstrated higher rates of respiratory depression
      (17.8-37%) in healthy, non-obese women receiving intrathecal opioids for post-cesarean
      analgesia.13,14 In addition, supplemental opioids are required in the majority of women
      receiving intrathecal morphine and may increase the risk of respiratory depression.11,14
      Anesthesiologists debate whether neuraxial opioids or intravenous patient controlled opioid
      analgesia (PCA) are the safest practice for postoperative analgesia in obese parturients
      following cesarean delivery. The ASA recommendations to employ neuraxial analgesia
      post-cesarean delivery does not differentiate between non-obese and obese women who now make
      up 30.3% in US women of child-bearing age.2 Obesity has been described as a risk factor for
      respiratory depression in those receiving opioids via any route of opioid
      administration,11,15, 17 but whether obesity itself is the risk factor or associated
      co-morbidities such as sleep apnea is debated.

      Studies are conflicting whether intrathecal opioids or patient controlled intravenous opioids
      cause more respiratory depression. Several studies have documented the incidence of
      respiratory depression with IV PCA; the rates range from 0.19% to 5.2%, which are equivalent
      or higher than those reported for intrathecal opioids. (Hagle 16). Dalchow et al.
      demonstrated higher rates of hypercapnia in patients receiving intrathecal opioid compared
      with those receiving intravenous opioid via patient controlled analgesia in nonobese women
      following cesarean delivery. (Dalchow)

      The Topological Oscillation Search with Kinematical Analysis (TOSCA) monitor allows a
      noninvasive method to measure transcutaneous carbon dioxide levels, with relative accuracy
      compared to arterial carbon dioxide monitoring.4-7 No studies have examined transcutaneous
      carbon dioxide levels in obese women following cesarean delivery using any form of
      postoperative analgesia. The investigators propose a randomized controlled trial using
      continuous transcutaneous carbon dioxide monitoring to evaluate the degree of respiratory
      depression in obese women receiving neuraxial opioid compared to intravenous opioid via PCA
      for post-cesarean analgesia.

      Two studies have demonstrated high rates of hypercapnia in non-obese women following
      administration of intrathecal morphine for cesarean delivery in the postpartum period.
      (Dalchow, Bauchat) Dalchow et al. demonstrated higher rates of hypercapnia in women receiving
      intrathecal diamorphine than intravenous morphine delivered via patient controlled analgesia.
      It is unclear whether intrathecal morphine causes more or less respiratory depression than
      intravenous opioid delivered via patient-controlled analgesia in obese women.

      This study will add to the understanding of respiratory function in the immediate postpartum
      period in obese women using opioids via intrathecal or intravenous routes. This study will
      better inform guidelines for the postpartum analgesic route of choice in the obese obstetric
      population and allow the investigators to make recommendations for the detection and
      prevention of respiratory depression after opioid administration in the obstetric population.

      Objective is to examine the transcutaneous carbon dioxide levels in obese women using either
      intrathecal morphine or intravenous patient-controlled hydromorphone for post-cesarean
      analgesia.

      The hypothesis is carbon dioxide levels will be significantly higher in obese women receiving
      intrathecal morphine versus obese women receiving intravenous patient controlled intravenous
      hydromorphone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of hypercapnia
time frame: 24 hours post delivery
description: Incidence of hypercapnia (transcutaneous CO2 levels >50mmHg) in the intrathecal morphine versus patient controlled intravenous morphine groups
measure: Opioid consumption
time frame: 24 hours post delivery
description: Amount of opioids used during the time from delivery to 24 hours post delivery
measure: NSAID consumption
time frame: 24 hours post delivery
description: Amount of NSAID's used during the time from delivery to 24 hours post delivery.
measure: Respiratory rate
time frame: 24 hours post delivery
description: Hourly respiratory rates for the first 12 hours then every 2 hours for the next 12 hours.
measure: Sedation scores
time frame: delivery to 12 hours post delivery
description: Sedation scores as scored on the Richmond Agitation and Sedation Scale at 2 hours, 6 hour and 12 hours post delivery.
measure: Pain Scores
time frame: 24 hours
description: Pain scores on a scale of 0 (low)-10 (high) will be documented every hour for the first 24 hours after delivery.
measure: Pulse oximetry
time frame: 24 hours post delivery
description: Pulse oximetry will be collected using the transcutaneous Co2 monitor for 24 hours after deliuvery.
arm group label: Intrathecal Morphine
arm group type: Active Comparator
description: Administration of 100µg intrathecal morphine to be given in the operative area.
arm group label: Intravenous Hydromorphone
arm group type: Active Comparator
description: Administration of intravenous hydromorphone give IV pca in the post operative area.
intervention type: Drug
intervention name: Intrathecal Morphine
description: Intrathecal Morphine administered in the operating room.
arm group label: Intrathecal Morphine
intervention type: Drug
intervention name: Intravenous hydromorphone
description: Intravenous hydromorphone administered via IV in the post operative area.
arm group label: Intravenous Hydromorphone
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Feyce Peralta, MD
role: Principal Investigator
affiliation: Northwestern University
country: United States
citation: Lee LA, Caplan RA, Stephens LS, Posner KL, Terman GW, Voepel-Lewis T, Domino KB. Postoperative opioid-induced respiratory depression: a closed claims analysis. Anesthesiology. 2015 Mar;122(3):659-65. doi: 10.1097/ALN.0000000000000564.
PMID: 25536092
citation: Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014 Feb 26;311(8):806-14. doi: 10.1001/jama.2014.732.
PMID: 24570244
citation: Practice Guidelines for the Prevention, Detection, and Management of Respiratory Depression Associated with Neuraxial Opioid Administration: An Updated Report by the American Society of Anesthesiologists Task Force on Neuraxial Opioids and the American Society of Regional Anesthesia and Pain Medicine. Anesthesiology. 2016 Mar;124(3):535-52. doi: 10.1097/ALN.0000000000000975. No abstract available.
PMID: 26655725
citation: McCormack JG, Kelly KP, Wedgwood J, Lyon R. The effects of different analgesic regimens on transcutaneous CO2 after major surgery. Anaesthesia. 2008 Aug;63(8):814-21. doi: 10.1111/j.1365-2044.2008.05487.x.
PMID: 18699897
responsible party type: Principal Investigator
investigator affiliation: Northwestern University
investigator full name: Feyce M. Peralta, MD, MS
investigator title: Principal Investigator
mesh term: Respiratory Insufficiency
mesh term: Pain, Postoperative
mesh term: Morphine
mesh term: Hydromorphone
sharing ipd: No