<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/NCT03258879</url>
  </required_header>
  <id_info>
    <org_study_id>10017388</org_study_id>
    <nct_id>NCT03258879</nct_id>
  </id_info>
  <brief_title>Comparison of Labor Analgesia Between Modified Combined Spinal-Epidural and Dural Puncture Epidural Techniques</brief_title>
  <official_title>Comparing the Quality of Labor Analgesia Between Modified Combined Spinal-Epidural and Dural Puncture Epidural Techniques: A Randomized Double Blinded Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Western University, Canada</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Western University, Canada</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>
      Epidural, Combined Spinal-Epidural, and more recently dural puncture epidural are forms of&#xD;
      neuraxial anesthesia used to provide pain relief in laboring women . The investigators want&#xD;
      to assess the onset of pain relief with 2 different neuraxial techniques performed at our&#xD;
      center, but which have not yet been compared in the literature: (1) Modified CSE, with only&#xD;
      local anesthetic injected into the spinal fluid to reduce side effects of opioids that are&#xD;
      seen with the traditional CSE and (2) Dural Puncture Epidural (DPE), involving puncture of&#xD;
      the spinal membrane, but without injection of medication into the spinal space. The&#xD;
      investigators hypothesize that the onset of labor analgesia will be faster with modified CSE&#xD;
      compared to DPE.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Purpose of the research:&#xD;
&#xD;
        -  To determine the onset of effective analgesia (Numerical Rating Scale (NRS) for pain &lt;/=&#xD;
           1/10 in minutes with the modified CSE and DPE techniques, which is our primary outcome.&#xD;
&#xD;
        -  To assess block quality (time to T10 sensory block, motor block, asymmetric block,&#xD;
           inadequate block) between the 2 techniques.&#xD;
&#xD;
        -  To assess incidence of breakthrough pain as determined by number of physician&#xD;
           interventions.&#xD;
&#xD;
        -  To determine the incidence of side effects (maternal hypotension, pruritus, nausea, and&#xD;
           fetal bradycardia).&#xD;
&#xD;
        -  To assess delivery outcomes (vaginal vs. instrumental vs. CS).&#xD;
&#xD;
        -  To compare fetal Apgar scores.&#xD;
&#xD;
        -  To assess maternal satisfaction with pain relief using Likert scale at 24h.&#xD;
&#xD;
        -  To evaluate for potential complications (Post-dural puncture headache, back pain, leg&#xD;
           weakness, numbness and infection) related to the techniques at 24h.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      The investigators hypothesize that the onset of effective analgesia (NRS pain &lt;/= 1, in&#xD;
      minutes) will be faster with the modified CSE compared to DPE.&#xD;
&#xD;
      Methodology:&#xD;
&#xD;
      Study Design: Randomized Double Blinded Clinical Trial.&#xD;
&#xD;
      Study Implementation:&#xD;
&#xD;
      Once participants are consented for the study, usual care is established with IV cannula&#xD;
      insertion, fluid bolus and standard monitors will be applied. Participants will then be&#xD;
      randomly assigned into two groups by a computer-generated randomization sequence. Group&#xD;
      assignments will be concealed in opaque numbered envelopes and will be opened by the&#xD;
      anesthesiologist performing the block immediately before initiation of analgesia. Group 1&#xD;
      will receive a modified combined spinal-epidural (MCSE) and Group 2 will receive a dural&#xD;
      puncture epidural (DPE).&#xD;
&#xD;
      The epidural space will be located at the L2-3 or L3-4 interspace using a midline approach&#xD;
      with a 17-G, 9 cm Touhy epidural needle using a loss of resistance technique. A single dural&#xD;
      puncture with confirmation of free flow of CSF will be performed with a 25-G, 12 cm Whitacre&#xD;
      needle placed through the epidural needle. Subsequent intervention varies with the group&#xD;
      allocation.&#xD;
&#xD;
      MCSE group: 1 ml of 0.25% bupivacaine will be injected intrathecally DPE group: No medication&#xD;
      will be injected intrathecally. Both the groups will subsequently have the epidural catheter&#xD;
      placed 4-6 cm into the space and will be checked for a negative aspiration of blood/CSF. In&#xD;
      the DPE group, 15 ml of 0.125% bupivacaine will be given as 5ml fractionated boluses. Both&#xD;
      groups will have patient controlled epidural analgesia started after the study interventions&#xD;
      as follows: Bupivacaine 1.25 mg/mL with fentanyl 2 microgram/ml, background infusion at 8&#xD;
      mL/h, demand dose of 4 mL, lockout interval of 20 minutes.&#xD;
&#xD;
      The anesthesiologist and nurse will be asked not to reveal the group assignment to the&#xD;
      patient or study co-investigators so that the patients and the study investigators collecting&#xD;
      the data will be blinded to the techniques. The anesthesiologist performing the technique&#xD;
      will prepare the medications according to group allocation and will not be involved in any&#xD;
      data collection. Attending, fellow or resident anesthesiologists will perform all the&#xD;
      techniques.&#xD;
&#xD;
      After block completion, an independent blinded co-investigator will assess the numerical&#xD;
      rating scale (NRS) pain scores from 0-10 and other outcomes after the initial dosing, at the&#xD;
      2, 4, 6, 8, 10, 15, 20 and 30 minute marks. The time taken to achieve a NRS equal to or less&#xD;
      than 1 will be recorded for all the three groups. Sensory levels will be assessed using ice&#xD;
      starting caudad at the S2 dermatome and moving cephalad. Time taken to achieve a block of T10&#xD;
      will be recorded. Patients will be assessed for pruritus and nausea/vomiting every hour, by&#xD;
      grading the severity on a scale ranging from 0-3; 0 = none, 1 = mild, 2= moderate and 3 =&#xD;
      severe. Motor strength will be assessed hourly with a modified Bromage score (0 = full&#xD;
      flexion of knees and ankles, 1 = partial flexion of knees, full flexion of ankles, 2 =&#xD;
      inability to flex knees and partial flexion of ankles and 3 = inability to flex knees and&#xD;
      ankles). Presence of motor blockade will be defined as modified Bromage score of more than or&#xD;
      equal to 1. Following the first 30 minutes, assessments will continue at 60-minute intervals&#xD;
      until delivery.&#xD;
&#xD;
      The participant will be monitored for hypotension and fetal bradycardia during this period&#xD;
      and up to 1 hour after the procedure. Hypotension is defined as a 20% reduction in the&#xD;
      systolic blood pressure from the admission blood pressure in the absence of uterine&#xD;
      contraction and will be treated with vasopressors as per the standard of care. Fetal&#xD;
      bradycardia is defined as a fetal heart rate of less than 100 beats per minute, persisting&#xD;
      for more than 1 minute.&#xD;
&#xD;
      In the event of inadequate analgesia and a unilateral block defined by a difference of more&#xD;
      than 2 dermatomal levels between the 2 sides, the participant will be placed on the less&#xD;
      blocked side and a supplemental epidural dose will be administered. If the unilateral block&#xD;
      persists, the catheter will be withdrawn 1 cm and an additional supplemental epidural dose of&#xD;
      5 ml 2% lidocaine will be given over 2 min. In the event of inadequate analgesia and the&#xD;
      presence of inadequate sensory level bilaterally, supplemental epidural dose will be&#xD;
      administered. If improvement of analgesia is not observed, the epidural catheter will be&#xD;
      replaced.&#xD;
&#xD;
      Mode of delivery and fetal Agar scores will be recorded for all the patients. All the study&#xD;
      subjects will be visited on postpartum day 1 and will be assessed for satisfaction with labor&#xD;
      analgesia using a Likert scale and any potential complications such as headache, back pain,&#xD;
      leg weakness or numbness and paresthesia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 2018</start_date>
  <completion_date type="Anticipated">August 2018</completion_date>
  <primary_completion_date type="Anticipated">August 2018</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison of the onset of effective analgesia between the study techniques</measure>
    <time_frame>1 year</time_frame>
    <description>Numerical Rating Scale (NRS) for pain &lt;/= 1/10 in minutes</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of block quality between the study techniques</measure>
    <time_frame>1 year</time_frame>
    <description>Time to T10 sensory block in minutes will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of the incidence of pruritus between the study techniques</measure>
    <time_frame>1 year</time_frame>
    <description>Participants will be assessed for pruritus every hour, by grading the severity on a scale ranging from 0-3; 0 = none, 1 = mild, 2= moderate and 3 = severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of the incidence of fetal bradycardia between the study techniques</measure>
    <time_frame>1 year</time_frame>
    <description>Fetal bradycardia is defined as a fetal heart rate of less than 100 beats per minute, persisting for more than 1 minute.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>To Determine the Onset of Analgesia (Numerical Rating Scale for Pain = 1) in Minutes</condition>
  <arm_group>
    <arm_group_label>Modified CSE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MCSE group: 1 ml of 0.25% bupivacaine will be injected intrathecally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dural puncture epidural</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dural puncture performed with a spinal needle, but no medication will be injected intrathecally.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Modified CSE</intervention_name>
    <description>MCSE group: 1 ml of 0.25% bupivacaine will be injected intrathecally</description>
    <arm_group_label>Modified CSE</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Dural puncture epidural</intervention_name>
    <description>DPE group: Dural puncture performed, but no medication will be injected intrathecally.</description>
    <arm_group_label>Dural puncture epidural</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ASA II healthy adult parturients, at 37-40 weeks gestation with singleton pregnancy&#xD;
             and vertex presentation.&#xD;
&#xD;
          -  Parturients in early labor with cervical dilatation less than 6 cm requesting epidural&#xD;
             analgesia&#xD;
&#xD;
          -  Parturients able to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient refusal to participate in the study.&#xD;
&#xD;
          -  Presence of clinically significant disease&#xD;
&#xD;
          -  Contraindications to neuraxial analgesia.&#xD;
&#xD;
          -  Presence of conditions associated with an increased risk of a cesarean delivery like&#xD;
             history of uterine anomaly or surgery, morbid obesity and known fetal anomalies or&#xD;
             non-reassuring fetal heart rate.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Pregnant patients</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Indu Singh, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Western University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yamini Subramani, MD</last_name>
    <phone>519-902-4715</phone>
    <email>yaminisrs@rediffmail.com</email>
  </overall_contact>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>July 12, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>November 9, 2017</last_update_submitted>
  <last_update_submitted_qc>November 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Combined spinal epidural analgesia, dural puncture epidural</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Agnosia</mesh_term>
  </condition_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/NCT03258879
org study id: 10017388
nct id: NCT03258879
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Epidural, Combined Spinal-Epidural, and more recently dural puncture epidural are forms of
      neuraxial anesthesia used to provide pain relief in laboring women . The investigators want
      to assess the onset of pain relief with 2 different neuraxial techniques performed at our
      center, but which have not yet been compared in the literature: (1) Modified CSE, with only
      local anesthetic injected into the spinal fluid to reduce side effects of opioids that are
      seen with the traditional CSE and (2) Dural Puncture Epidural (DPE), involving puncture of
      the spinal membrane, but without injection of medication into the spinal space. The
      investigators hypothesize that the onset of labor analgesia will be faster with modified CSE
      compared to DPE.
Purpose of the research:

        -  To determine the onset of effective analgesia (Numerical Rating Scale (NRS) for pain </=
           1/10 in minutes with the modified CSE and DPE techniques, which is our primary outcome.

        -  To assess block quality (time to T10 sensory block, motor block, asymmetric block,
           inadequate block) between the 2 techniques.

        -  To assess incidence of breakthrough pain as determined by number of physician
           interventions.

        -  To determine the incidence of side effects (maternal hypotension, pruritus, nausea, and
           fetal bradycardia).

        -  To assess delivery outcomes (vaginal vs. instrumental vs. CS).

        -  To compare fetal Apgar scores.

        -  To assess maternal satisfaction with pain relief using Likert scale at 24h.

        -  To evaluate for potential complications (Post-dural puncture headache, back pain, leg
           weakness, numbness and infection) related to the techniques at 24h.

      Hypothesis:

      The investigators hypothesize that the onset of effective analgesia (NRS pain </= 1, in
      minutes) will be faster with the modified CSE compared to DPE.

      Methodology:

      Study Design: Randomized Double Blinded Clinical Trial.

      Study Implementation:

      Once participants are consented for the study, usual care is established with IV cannula
      insertion, fluid bolus and standard monitors will be applied. Participants will then be
      randomly assigned into two groups by a computer-generated randomization sequence. Group
      assignments will be concealed in opaque numbered envelopes and will be opened by the
      anesthesiologist performing the block immediately before initiation of analgesia. Group 1
      will receive a modified combined spinal-epidural (MCSE) and Group 2 will receive a dural
      puncture epidural (DPE).

      The epidural space will be located at the L2-3 or L3-4 interspace using a midline approach
      with a 17-G, 9 cm Touhy epidural needle using a loss of resistance technique. A single dural
      puncture with confirmation of free flow of CSF will be performed with a 25-G, 12 cm Whitacre
      needle placed through the epidural needle. Subsequent intervention varies with the group
      allocation.

      MCSE group: 1 ml of 0.25% bupivacaine will be injected intrathecally DPE group: No medication
      will be injected intrathecally. Both the groups will subsequently have the epidural catheter
      placed 4-6 cm into the space and will be checked for a negative aspiration of blood/CSF. In
      the DPE group, 15 ml of 0.125% bupivacaine will be given as 5ml fractionated boluses. Both
      groups will have patient controlled epidural analgesia started after the study interventions
      as follows: Bupivacaine 1.25 mg/mL with fentanyl 2 microgram/ml, background infusion at 8
      mL/h, demand dose of 4 mL, lockout interval of 20 minutes.

      The anesthesiologist and nurse will be asked not to reveal the group assignment to the
      patient or study co-investigators so that the patients and the study investigators collecting
      the data will be blinded to the techniques. The anesthesiologist performing the technique
      will prepare the medications according to group allocation and will not be involved in any
      data collection. Attending, fellow or resident anesthesiologists will perform all the
      techniques.

      After block completion, an independent blinded co-investigator will assess the numerical
      rating scale (NRS) pain scores from 0-10 and other outcomes after the initial dosing, at the
      2, 4, 6, 8, 10, 15, 20 and 30 minute marks. The time taken to achieve a NRS equal to or less
      than 1 will be recorded for all the three groups. Sensory levels will be assessed using ice
      starting caudad at the S2 dermatome and moving cephalad. Time taken to achieve a block of T10
      will be recorded. Patients will be assessed for pruritus and nausea/vomiting every hour, by
      grading the severity on a scale ranging from 0-3; 0 = none, 1 = mild, 2= moderate and 3 =
      severe. Motor strength will be assessed hourly with a modified Bromage score (0 = full
      flexion of knees and ankles, 1 = partial flexion of knees, full flexion of ankles, 2 =
      inability to flex knees and partial flexion of ankles and 3 = inability to flex knees and
      ankles). Presence of motor blockade will be defined as modified Bromage score of more than or
      equal to 1. Following the first 30 minutes, assessments will continue at 60-minute intervals
      until delivery.

      The participant will be monitored for hypotension and fetal bradycardia during this period
      and up to 1 hour after the procedure. Hypotension is defined as a 20% reduction in the
      systolic blood pressure from the admission blood pressure in the absence of uterine
      contraction and will be treated with vasopressors as per the standard of care. Fetal
      bradycardia is defined as a fetal heart rate of less than 100 beats per minute, persisting
      for more than 1 minute.

      In the event of inadequate analgesia and a unilateral block defined by a difference of more
      than 2 dermatomal levels between the 2 sides, the participant will be placed on the less
      blocked side and a supplemental epidural dose will be administered. If the unilateral block
      persists, the catheter will be withdrawn 1 cm and an additional supplemental epidural dose of
      5 ml 2% lidocaine will be given over 2 min. In the event of inadequate analgesia and the
      presence of inadequate sensory level bilaterally, supplemental epidural dose will be
      administered. If improvement of analgesia is not observed, the epidural catheter will be
      replaced.

      Mode of delivery and fetal Agar scores will be recorded for all the patients. All the study
      subjects will be visited on postpartum day 1 and will be assessed for satisfaction with labor
      analgesia using a Likert scale and any potential complications such as headache, back pain,
      leg weakness or numbness and paresthesia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Comparison of the onset of effective analgesia between the study techniques
time frame: 1 year
description: Numerical Rating Scale (NRS) for pain </= 1/10 in minutes
measure: Comparison of block quality between the study techniques
time frame: 1 year
description: Time to T10 sensory block in minutes will be measured
measure: Comparison of the incidence of pruritus between the study techniques
time frame: 1 year
description: Participants will be assessed for pruritus every hour, by grading the severity on a scale ranging from 0-3; 0 = none, 1 = mild, 2= moderate and 3 = severe
measure: Comparison of the incidence of fetal bradycardia between the study techniques
time frame: 1 year
description: Fetal bradycardia is defined as a fetal heart rate of less than 100 beats per minute, persisting for more than 1 minute.
arm group label: Modified CSE
arm group type: Experimental
description: MCSE group: 1 ml of 0.25% bupivacaine will be injected intrathecally
arm group label: Dural puncture epidural
arm group type: Active Comparator
description: Dural puncture performed with a spinal needle, but no medication will be injected intrathecally.
intervention type: Procedure
intervention name: Modified CSE
description: MCSE group: 1 ml of 0.25% bupivacaine will be injected intrathecally
arm group label: Modified CSE
intervention type: Procedure
intervention name: Dural puncture epidural
description: DPE group: Dural puncture performed, but no medication will be injected intrathecally.
arm group label: Dural puncture epidural
criteria: 
gender: Female
gender based: Yes
gender description: Pregnant patients
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Indu Singh, MD, FRCPC
role: Principal Investigator
affiliation: Western University
last name: Yamini Subramani, MD
phone: 519-902-4715
email: yaminisrs@rediffmail.com
responsible party type: Sponsor
mesh term: Agnosia
sharing ipd: No