<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/NCT03232918</url>
  </required_header>
  <id_info>
    <org_study_id>201609722</org_study_id>
    <nct_id>NCT03232918</nct_id>
  </id_info>
  <brief_title>Oxytocin and Fetal Heart Rate Changes</brief_title>
  <official_title>A Randomized Controlled Trial Evaluating the Effect of the Oxytocin Infusion Rate on Fetal Heart Rate Changes and Maternal-Fetal Outcomes During the Initiation of Combined Spinal-Epidural Labor Analgesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Unyime Ituk</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Iowa</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The reported risk of nonreassuring fetal heart trace following neuraxial analgesia is 3-23%.&#xD;
      This variability may be due to fluid and oxytocin management prior to and during the&#xD;
      initiation of neuraxial analgesia. The study hypothesis is that decreasing the oxytocin&#xD;
      infusion rate by 50 % prior to initiation of combined spinal epidural analgesia will cause a&#xD;
      reduction in the incidence of adverse fetal heart rate changes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Oxytocin is used in labor and delivery to increase the frequency of contractions and augment&#xD;
      uterine contractile strength, thereby establishing a regular pattern of labor. However, the&#xD;
      administration of exogenous oxytocin in the presence of an uncoordinated labor pattern&#xD;
      confers a risk for an increase in uterine contraction frequency, resulting in inadequate&#xD;
      relaxation periods. This leads to an increase in the basal tone of the uterus, which may lead&#xD;
      to a tetanic contraction with the risk of decreased uteroplacental blood flow and fetal&#xD;
      hypoxemia. Previous studies investigating low- versus high-dose oxytocin for induction or&#xD;
      augmentation of labor have had conflicting results on the effect on fetal heart rate&#xD;
      abnormalities. One of the limitations of these studies is that the labor analgesia was not&#xD;
      standardized. The combination of low-dose combined spinal epidural analgesia and the high/low&#xD;
      dose oxytocin have not been evaluated. One of the proposed mechanisms for nonreassuring fetal&#xD;
      heart a tracing after initiation of analgesia is that the pain relief from neuraxial&#xD;
      analgesia causes a decrease in catecholamine release by the sympathetic nervous system. The&#xD;
      subsequent decrease in the circulating epinephrine concentration contributes to an increase&#xD;
      in uterine tone, as epinephrine is a potent tocolytic agent. The increased tone, in turn,&#xD;
      leads to a decrease in placental blood flow, and eventually fetal bradycardia. The primary&#xD;
      outcome of this study is the incidence of non-reassuring fetal heart rate tracings within the&#xD;
      first 60 minutes after the placement of combined spinal epidural analgesia&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 20, 2019</start_date>
  <completion_date type="Anticipated">April 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2024</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>The labor room nurse will be aware of the patient group assignment and will adjust the dose of the drug based on group assignment. The Investigator, Physician Provider and Outcome Assessor will be blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of non-reassuring fetal heart rate tracings</measure>
    <time_frame>1.5 hours</time_frame>
    <description>Fetal heart rate tracings will be examined for 30 minutes before and 60 minutes after the initiation of combined spinal epidural analgesia</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of oxytocin dose on duration of 1st and 2nd stage of labor</measure>
    <time_frame>24 hours</time_frame>
    <description>The effect of the intervention on the duration of labor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mode of delivery</measure>
    <time_frame>24 hours</time_frame>
    <description>The effect of the intervention on the rate of spontaneous vaginal delivery, instrumental vaginal delivery and cesarean delivery</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">730</enrollment>
  <condition>Fetal Bradycardia Complicating Labor and Delivery</condition>
  <condition>Fetal Bradycardia During Labor</condition>
  <condition>Fetal Heart Rate or Rhythm Abnormality Affecting Fetus</condition>
  <arm_group>
    <arm_group_label>Standard Dose Oxytocin</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients randomized to the standard dose oxytocin will have their oxytocin infusion maintained at the standard of care protocol prior to placement of a combined spinal epidural for labor analgesia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Half Dose Oxytocin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to the half dose oxytocin will have their oxytocin infusion reduced by 50 % prior to placement of a combined spinal epidural for labor analgesia.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Half dose Oxytocin</intervention_name>
    <description>Patients randomized to the half dose oxytocin group will have the oxytocin infusion reduced to 50 % prior to placement of combined spinal epidural for labor analgesia</description>
    <arm_group_label>Half Dose Oxytocin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy nulliparous or multiparous women at term (37 &gt; weeks' gestation)&#xD;
&#xD;
          -  Singleton pregnancy&#xD;
&#xD;
          -  Request for neuraxial analgesia&#xD;
&#xD;
          -  Oxytocin used for induction of labor or augmentation of labor per institutional&#xD;
             protocols&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of chronic analgesic medications&#xD;
&#xD;
          -  Prior administration of systemic opioid labor analgesia&#xD;
&#xD;
          -  Non-vertex presentation&#xD;
&#xD;
          -  Contraindication to neuraxial analgesia&#xD;
&#xD;
          -  Category 3 fetal heart rate tracing prior to the initiation of combined spinal&#xD;
             epidural analgesia&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Unyime Ituk</last_name>
    <role>Study Director</role>
    <affiliation>University of Iowa</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Unyime Ituk</last_name>
    <phone>319-356-2633</phone>
    <email>unyime-ituk@uiowa.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Iowa Hospitals and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52245</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Unyime Ituk, MD</last_name>
      <phone>319-356-2633</phone>
      <email>unyime-ituk@uiowa.edu</email>
    </contact>
    <contact_backup>
      <last_name>Zita A Sibenaller, PhD</last_name>
      <phone>319-356-8878</phone>
      <email>zita-sibenaller@uiowa.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Meredith Albrecht, MD</last_name>
      <email>maaalbrecht@mcw.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
  </removed_countries>
  <reference>
    <citation>Mardirosoff C, Dumont L, Boulvain M, Tramer MR. Fetal bradycardia due to intrathecal opioids for labour analgesia: a systematic review. BJOG. 2002 Mar;109(3):274-81. doi: 10.1111/j.1471-0528.2002.01380.x.</citation>
    <PMID>11950182</PMID>
  </reference>
  <reference>
    <citation>Abrao KC, Francisco RPV, Miyadahira S, Cicarelli DD, Zugaib M. Elevation of uterine basal tone and fetal heart rate abnormalities after labor analgesia: a randomized controlled trial. Obstet Gynecol. 2009 Jan;113(1):41-47. doi: 10.1097/AOG.0b013e31818f5eb6.</citation>
    <PMID>19104358</PMID>
  </reference>
  <reference>
    <citation>Clarke VT, Smiley RM, Finster M. Uterine hyperactivity after intrathecal injection of fentanyl for analgesia during labor: a cause of fetal bradycardia? Anesthesiology. 1994 Oct;81(4):1083. doi: 10.1097/00000542-199410000-00041. No abstract available.</citation>
    <PMID>7943823</PMID>
  </reference>
  <reference>
    <citation>Satin AJ, Leveno KJ, Sherman ML, Brewster DS, Cunningham FG. High- versus low-dose oxytocin for labor stimulation. Obstet Gynecol. 1992 Jul;80(1):111-6.</citation>
    <PMID>1603479</PMID>
  </reference>
  <reference>
    <citation>Budden A, Chen LJ, Henry A. High-dose versus low-dose oxytocin infusion regimens for induction of labour at term. Cochrane Database Syst Rev. 2014 Oct 9;2014(10):CD009701. doi: 10.1002/14651858.CD009701.pub2.</citation>
    <PMID>25300173</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <last_update_submitted>May 11, 2023</last_update_submitted>
  <last_update_submitted_qc>May 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Iowa</investigator_affiliation>
    <investigator_full_name>Unyime Ituk</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bradycardia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxytocin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All of the individual participant data collected during the trial, after de-identification will be shared with researchers who provide a methodologically sound proposal, to achieve aims in the approved proposal. IPD will be available for sharing immediately after publication and ending 5 years following article publication.</ipd_description>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>IPD will be available for sharing immediately after publication and ending 5 years following article publication.</ipd_time_frame>
    <ipd_access_criteria>IPD will be accessible to researchers who provide a methodologically sound proposal, to achieve aims in the approved proposal</ipd_access_criteria>
  </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/NCT03232918
org study id: 201609722
nct id: NCT03232918
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The reported risk of nonreassuring fetal heart trace following neuraxial analgesia is 3-23%.
      This variability may be due to fluid and oxytocin management prior to and during the
      initiation of neuraxial analgesia. The study hypothesis is that decreasing the oxytocin
      infusion rate by 50 % prior to initiation of combined spinal epidural analgesia will cause a
      reduction in the incidence of adverse fetal heart rate changes.
Oxytocin is used in labor and delivery to increase the frequency of contractions and augment
      uterine contractile strength, thereby establishing a regular pattern of labor. However, the
      administration of exogenous oxytocin in the presence of an uncoordinated labor pattern
      confers a risk for an increase in uterine contraction frequency, resulting in inadequate
      relaxation periods. This leads to an increase in the basal tone of the uterus, which may lead
      to a tetanic contraction with the risk of decreased uteroplacental blood flow and fetal
      hypoxemia. Previous studies investigating low- versus high-dose oxytocin for induction or
      augmentation of labor have had conflicting results on the effect on fetal heart rate
      abnormalities. One of the limitations of these studies is that the labor analgesia was not
      standardized. The combination of low-dose combined spinal epidural analgesia and the high/low
      dose oxytocin have not been evaluated. One of the proposed mechanisms for nonreassuring fetal
      heart a tracing after initiation of analgesia is that the pain relief from neuraxial
      analgesia causes a decrease in catecholamine release by the sympathetic nervous system. The
      subsequent decrease in the circulating epinephrine concentration contributes to an increase
      in uterine tone, as epinephrine is a potent tocolytic agent. The increased tone, in turn,
      leads to a decrease in placental blood flow, and eventually fetal bradycardia. The primary
      outcome of this study is the incidence of non-reassuring fetal heart rate tracings within the
      first 60 minutes after the placement of combined spinal epidural analgesia
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: The labor room nurse will be aware of the patient group assignment and will adjust the dose of the drug based on group assignment. The Investigator, Physician Provider and Outcome Assessor will be blinded.
measure: Incidence of non-reassuring fetal heart rate tracings
time frame: 1.5 hours
description: Fetal heart rate tracings will be examined for 30 minutes before and 60 minutes after the initiation of combined spinal epidural analgesia
measure: Effect of oxytocin dose on duration of 1st and 2nd stage of labor
time frame: 24 hours
description: The effect of the intervention on the duration of labor
measure: Mode of delivery
time frame: 24 hours
description: The effect of the intervention on the rate of spontaneous vaginal delivery, instrumental vaginal delivery and cesarean delivery
arm group label: Standard Dose Oxytocin
arm group type: No Intervention
description: Patients randomized to the standard dose oxytocin will have their oxytocin infusion maintained at the standard of care protocol prior to placement of a combined spinal epidural for labor analgesia
arm group label: Half Dose Oxytocin
arm group type: Experimental
description: Patients randomized to the half dose oxytocin will have their oxytocin infusion reduced by 50 % prior to placement of a combined spinal epidural for labor analgesia.
intervention type: Drug
intervention name: Half dose Oxytocin
description: Patients randomized to the half dose oxytocin group will have the oxytocin infusion reduced to 50 % prior to placement of combined spinal epidural for labor analgesia
arm group label: Half Dose Oxytocin
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Unyime Ituk
role: Study Director
affiliation: University of Iowa
last name: Unyime Ituk
phone: 319-356-2633
email: unyime-ituk@uiowa.edu
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Not yet recruiting
contact: 
country: United States
country: Canada
citation: Mardirosoff C, Dumont L, Boulvain M, Tramer MR. Fetal bradycardia due to intrathecal opioids for labour analgesia: a systematic review. BJOG. 2002 Mar;109(3):274-81. doi: 10.1111/j.1471-0528.2002.01380.x.
PMID: 11950182
citation: Abrao KC, Francisco RPV, Miyadahira S, Cicarelli DD, Zugaib M. Elevation of uterine basal tone and fetal heart rate abnormalities after labor analgesia: a randomized controlled trial. Obstet Gynecol. 2009 Jan;113(1):41-47. doi: 10.1097/AOG.0b013e31818f5eb6.
PMID: 19104358
citation: Clarke VT, Smiley RM, Finster M. Uterine hyperactivity after intrathecal injection of fentanyl for analgesia during labor: a cause of fetal bradycardia? Anesthesiology. 1994 Oct;81(4):1083. doi: 10.1097/00000542-199410000-00041. No abstract available.
PMID: 7943823
citation: Satin AJ, Leveno KJ, Sherman ML, Brewster DS, Cunningham FG. High- versus low-dose oxytocin for labor stimulation. Obstet Gynecol. 1992 Jul;80(1):111-6.
PMID: 1603479
citation: Budden A, Chen LJ, Henry A. High-dose versus low-dose oxytocin infusion regimens for induction of labour at term. Cochrane Database Syst Rev. 2014 Oct 9;2014(10):CD009701. doi: 10.1002/14651858.CD009701.pub2.
PMID: 25300173
responsible party type: Sponsor-Investigator
investigator affiliation: University of Iowa
investigator full name: Unyime Ituk
investigator title: Associate Professor
mesh term: Bradycardia
mesh term: Oxytocin
sharing ipd: Yes
ipd description: All of the individual participant data collected during the trial, after de-identification will be shared with researchers who provide a methodologically sound proposal, to achieve aims in the approved proposal. IPD will be available for sharing immediately after publication and ending 5 years following article publication.
ipd info type: Clinical Study Report (CSR)
ipd time frame: IPD will be available for sharing immediately after publication and ending 5 years following article publication.
ipd access criteria: IPD will be accessible to researchers who provide a methodologically sound proposal, to achieve aims in the approved proposal