<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/NCT04468568</url>
  </required_header>
  <id_info>
    <org_study_id>00607219.4.0030.0099</org_study_id>
    <nct_id>NCT04468568</nct_id>
  </id_info>
  <brief_title>In Utero Repair of Myelomeningocele: Atosiban Versus Terbutaline</brief_title>
  <official_title>Assessment of Maternal Blood Gas Changes When Using Atosiban and Terbutaline as Tocolytic Agents, During in Utero Repair of Myelomeningocele</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sao Paulo General Hospital</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>
      Myelomeningocele is a malformation with high incidence, and it consists in a neural tube&#xD;
      defect. Fetal intrauterine surgery is an alternative for correction, and it improves the&#xD;
      prognosis of the fetus, but has an increased risk of maternal complications and premature&#xD;
      labor, as it can occur due to uterine stimulation. It is therefore essential that tocolysis&#xD;
      is performed before, during and after surgery, and the most commonly used tocolytics are&#xD;
      terbutaline and atosiban. Terbutaline has no specificity and may have several adverse effects&#xD;
      such as maternal acidosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of the study was to evaluate maternal blood gas alterations among cases that&#xD;
      used atosiban tocolytic agent and cases with terbutaline in in utero repair of&#xD;
      myelomeningocele. It consists of a retrospective cohort study. It included 25 patients, who&#xD;
      were divided into two groups, depending on which agent they received as main tocolytic agent&#xD;
      during the intrauterine fetal myelomeningocele repair: terbutalineor atosiban. The primary&#xD;
      outcome was maternal arterial pH at the end of surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Actual">April 1, 2022</completion_date>
  <primary_completion_date type="Actual">January 31, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Maternal arterial blood pH at the start of surgery</measure>
    <time_frame>Right after intubation</time_frame>
    <description>Arterial blood pH</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maternal arterial blood pH at the end of surgery</measure>
    <time_frame>Before extubation</time_frame>
    <description>Arterial blood pH</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maternal arterial blood pH at 120 minutes after surgery</measure>
    <time_frame>Two hours after the end of surgery</time_frame>
    <description>Arterial blood pH</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Short-term fetal repercussions</measure>
    <time_frame>In the end of the surgery, before extubation</time_frame>
    <description>Fetal heart rate in the immediate postoperative period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-term fetal repercussions</measure>
    <time_frame>At the birth</time_frame>
    <description>Gestational age at birth</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">25</enrollment>
  <condition>Myelomeningocele</condition>
  <condition>Terbutaline Adverse Reaction</condition>
  <condition>Pregnancy; Malformation Central Nervous System</condition>
  <arm_group>
    <arm_group_label>Atosiban</arm_group_label>
    <description>Intravenous Atosiban as main tocolytic agent</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Terbutaline</arm_group_label>
    <description>Intravenous Terbutaline as main tocolytic agent</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atosiban</intervention_name>
    <description>Atosiban intravenous. Dose: attack of 6.75 mg, and maintenance of 300 mcg / min for 3 hours, and 100 mcg / min for 21 hours.</description>
    <arm_group_label>Atosiban</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Terbutaline</intervention_name>
    <description>Terbutaline intravenous. Dose: 2.5 mg in 500 mL saline, infusion rate of 30 mL / hr (150 mcg / h) during the surgery and for 24 hours.</description>
    <arm_group_label>Terbutaline</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who underwent intrauterine myelomeningocele surgical repair in a tertiary&#xD;
        obstetrical center (Hospital das Clínicas da Faculdade de Medicina da Universidade de São&#xD;
        Paulo), from November of 2017 to January of 2020.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pregnant women over 18 years&#xD;
&#xD;
          -  Single fetus pregnancy&#xD;
&#xD;
          -  Fetus with myelomeningocele&#xD;
&#xD;
          -  Gestational age from 19 to 26&#xD;
&#xD;
          -  Fetus with normal karyotype&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Multiple pregnancy&#xD;
&#xD;
          -  Fetal abnormality not related to myelomeningocele&#xD;
&#xD;
          -  Kyphosis greater than or equal to 30 degrees&#xD;
&#xD;
          -  Placenta previa&#xD;
&#xD;
          -  Maternal disease that increases the risk of pregnancy (insulin-dependent DM,&#xD;
             hypertension poorly controlled)&#xD;
&#xD;
          -  History of incompetent cervix&#xD;
&#xD;
          -  Carrier of HIV, hepatitis B or hepatitis C&#xD;
&#xD;
          -  Maternal-fetal isoimmunization&#xD;
&#xD;
          -  Uterine Alteration&#xD;
&#xD;
          -  Obesity (IMC greater than 30)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elaine I Moura, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital das Clinicas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hermann S Fernandes, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital das Clinicas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Faculdade de Medicina da Universidade de São Paulo</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <results_reference>
    <citation>Ferschl M, Ball R, Lee H, Rollins MD. Anesthesia for in utero repair of myelomeningocele. Anesthesiology. 2013 May;118(5):1211-23. doi: 10.1097/ALN.0b013e31828ea597.</citation>
    <PMID>23508219</PMID>
  </results_reference>
  <results_reference>
    <citation>Boulet SL, Yang Q, Mai C, Kirby RS, Collins JS, Robbins JM, Meyer R, Canfield MA, Mulinare J; National Birth Defects Prevention Network. Trends in the postfortification prevalence of spina bifida and anencephaly in the United States. Birth Defects Res A Clin Mol Teratol. 2008 Jul;82(7):527-32. doi: 10.1002/bdra.20468.</citation>
    <PMID>18481813</PMID>
  </results_reference>
  <results_reference>
    <citation>Fichter MA, Dornseifer U, Henke J, Schneider KT, Kovacs L, Biemer E, Bruner J, Adzick NS, Harrison MR, Papadopulos NA. Fetal spina bifida repair--current trends and prospects of intrauterine neurosurgery. Fetal Diagn Ther. 2008;23(4):271-86. doi: 10.1159/000123614. Epub 2008 Apr 14.</citation>
    <PMID>18417993</PMID>
  </results_reference>
  <results_reference>
    <citation>Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D'Alton ME, Farmer DL; MOMS Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med. 2011 Mar 17;364(11):993-1004. doi: 10.1056/NEJMoa1014379. Epub 2011 Feb 9.</citation>
    <PMID>21306277</PMID>
  </results_reference>
  <results_reference>
    <citation>Fisk NM, Gitau R, Teixeira JM, Giannakoulopoulos X, Cameron AD, Glover VA. Effect of direct fetal opioid analgesia on fetal hormonal and hemodynamic stress response to intrauterine needling. Anesthesiology. 2001 Oct;95(4):828-35. doi: 10.1097/00000542-200110000-00008.</citation>
    <PMID>11605920</PMID>
  </results_reference>
  <results_reference>
    <citation>Cauldwell CB. Anesthesia for fetal surgery. Anesthesiol Clin North Am. 2002 Mar;20(1):211-26. doi: 10.1016/s0889-8537(03)00062-2.</citation>
    <PMID>11892506</PMID>
  </results_reference>
  <results_reference>
    <citation>Devoto JC, Alcalde JL, Otayza F, Sepulveda W. Anesthesia for myelomeningocele surgery in fetus. Childs Nerv Syst. 2017 Jul;33(7):1169-1175. doi: 10.1007/s00381-017-3437-7. Epub 2017 May 25.</citation>
    <PMID>28547209</PMID>
  </results_reference>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>March 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>June 2, 2022</last_update_submitted>
  <last_update_submitted_qc>June 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo General Hospital</investigator_affiliation>
    <investigator_full_name>Hermann dos Santos Fernandes</investigator_full_name>
    <investigator_title>Attending Anesthetist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meningomyelocele</mesh_term>
    <mesh_term>Spina Bifida Cystica</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Terbutaline</mesh_term>
    <mesh_term>Atosiban</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The IPD sharing plan includes informations about the demographic sample, the results of the study and the statistical analysis</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>From October/2017 until January/2021</ipd_time_frame>
    <ipd_access_criteria>Contact through email</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/NCT04468568
org study id: 00607219.4.0030.0099
nct id: NCT04468568
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Myelomeningocele is a malformation with high incidence, and it consists in a neural tube
      defect. Fetal intrauterine surgery is an alternative for correction, and it improves the
      prognosis of the fetus, but has an increased risk of maternal complications and premature
      labor, as it can occur due to uterine stimulation. It is therefore essential that tocolysis
      is performed before, during and after surgery, and the most commonly used tocolytics are
      terbutaline and atosiban. Terbutaline has no specificity and may have several adverse effects
      such as maternal acidosis.
The objective of the study was to evaluate maternal blood gas alterations among cases that
      used atosiban tocolytic agent and cases with terbutaline in in utero repair of
      myelomeningocele. It consists of a retrospective cohort study. It included 25 patients, who
      were divided into two groups, depending on which agent they received as main tocolytic agent
      during the intrauterine fetal myelomeningocele repair: terbutalineor atosiban. The primary
      outcome was maternal arterial pH at the end of surgery.
observational model: Cohort
time perspective: Retrospective
measure: Maternal arterial blood pH at the start of surgery
time frame: Right after intubation
description: Arterial blood pH
measure: Maternal arterial blood pH at the end of surgery
time frame: Before extubation
description: Arterial blood pH
measure: Maternal arterial blood pH at 120 minutes after surgery
time frame: Two hours after the end of surgery
description: Arterial blood pH
measure: Short-term fetal repercussions
time frame: In the end of the surgery, before extubation
description: Fetal heart rate in the immediate postoperative period
measure: Long-term fetal repercussions
time frame: At the birth
description: Gestational age at birth
arm group label: Atosiban
description: Intravenous Atosiban as main tocolytic agent
arm group label: Terbutaline
description: Intravenous Terbutaline as main tocolytic agent
intervention type: Drug
intervention name: Atosiban
description: Atosiban intravenous. Dose: attack of 6.75 mg, and maintenance of 300 mcg / min for 3 hours, and 100 mcg / min for 21 hours.
arm group label: Atosiban
intervention type: Drug
intervention name: Terbutaline
description: Terbutaline intravenous. Dose: 2.5 mg in 500 mL saline, infusion rate of 30 mL / hr (150 mcg / h) during the surgery and for 24 hours.
arm group label: Terbutaline
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Elaine I Moura, MD
role: Principal Investigator
affiliation: Hospital das Clinicas
last name: Hermann S Fernandes, PhD
role: Principal Investigator
affiliation: Hospital das Clinicas
facility: 
country: Brazil
citation: Ferschl M, Ball R, Lee H, Rollins MD. Anesthesia for in utero repair of myelomeningocele. Anesthesiology. 2013 May;118(5):1211-23. doi: 10.1097/ALN.0b013e31828ea597.
PMID: 23508219
citation: Boulet SL, Yang Q, Mai C, Kirby RS, Collins JS, Robbins JM, Meyer R, Canfield MA, Mulinare J; National Birth Defects Prevention Network. Trends in the postfortification prevalence of spina bifida and anencephaly in the United States. Birth Defects Res A Clin Mol Teratol. 2008 Jul;82(7):527-32. doi: 10.1002/bdra.20468.
PMID: 18481813
citation: Fichter MA, Dornseifer U, Henke J, Schneider KT, Kovacs L, Biemer E, Bruner J, Adzick NS, Harrison MR, Papadopulos NA. Fetal spina bifida repair--current trends and prospects of intrauterine neurosurgery. Fetal Diagn Ther. 2008;23(4):271-86. doi: 10.1159/000123614. Epub 2008 Apr 14.
PMID: 18417993
citation: Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D'Alton ME, Farmer DL; MOMS Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med. 2011 Mar 17;364(11):993-1004. doi: 10.1056/NEJMoa1014379. Epub 2011 Feb 9.
PMID: 21306277
citation: Fisk NM, Gitau R, Teixeira JM, Giannakoulopoulos X, Cameron AD, Glover VA. Effect of direct fetal opioid analgesia on fetal hormonal and hemodynamic stress response to intrauterine needling. Anesthesiology. 2001 Oct;95(4):828-35. doi: 10.1097/00000542-200110000-00008.
PMID: 11605920
citation: Cauldwell CB. Anesthesia for fetal surgery. Anesthesiol Clin North Am. 2002 Mar;20(1):211-26. doi: 10.1016/s0889-8537(03)00062-2.
PMID: 11892506
citation: Devoto JC, Alcalde JL, Otayza F, Sepulveda W. Anesthesia for myelomeningocele surgery in fetus. Childs Nerv Syst. 2017 Jul;33(7):1169-1175. doi: 10.1007/s00381-017-3437-7. Epub 2017 May 25.
PMID: 28547209
responsible party type: Principal Investigator
investigator affiliation: University of Sao Paulo General Hospital
investigator full name: Hermann dos Santos Fernandes
investigator title: Attending Anesthetist
mesh term: Meningomyelocele
mesh term: Spina Bifida Cystica
mesh term: Terbutaline
mesh term: Atosiban
sharing ipd: Yes
ipd description: The IPD sharing plan includes informations about the demographic sample, the results of the study and the statistical analysis
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: From October/2017 until January/2021
ipd access criteria: Contact through email