<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/NCT04496050</url>
  </required_header>
  <id_info>
    <org_study_id>KA-19044</org_study_id>
    <nct_id>NCT04496050</nct_id>
  </id_info>
  <brief_title>Effects of Prostaglandin E1 Treatment on Pyloric Wall in Newborns</brief_title>
  <acronym>EOPTOPWT</acronym>
  <official_title>Effect Of Prostaglandin E1 Treatment On Pyloric Wall Thickness in Newborns With Ductal Dependent Critical Congenital Heart Diseases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hacettepe University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hacettepe University</source>
  <oversight_info>
    <has_dmc>No</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>
      Prostaglandin E1 (PGE1) has been used in the medical treatment of ductal dependent critical&#xD;
      congenital heart disease in neonates. Apnea/ bradycardia, hypotension, hypokalemia, feeding&#xD;
      difficulties, fever, jitteriness are the most important side effects of PGE1. Also gastric&#xD;
      outlet has been reported.&#xD;
&#xD;
      We aimed to determine effect of PGE1 treatment on pyloric wall thickness in newborn period.&#xD;
      In this study, the side effect of increase of pylorus muscle wall thickness will be monitored&#xD;
      with weekly ultrasonography. No intervention in the treatment, medical decisions and&#xD;
      follow-up of these patients will be made. After reaching the sufficient number of cases (20&#xD;
      cases), increases in the pyloric wall thickness dimensions will be compared with statistical&#xD;
      analysis. The number of cases was determined in accordance with the rate of hospitalization&#xD;
      in our unit during the determined period (18 months).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intravenous prostaglandin E1 infusion is referred to as ductus dependent diseases, in&#xD;
      systemic (aortic blood flow) circulation (eg critical aortic coarctation, intermittent arcus&#xD;
      aorta, hypoplastic left heart, transposition of great artery), or lung blood flow through&#xD;
      patent ductus arteriosus ( For example, pulmonary valve atresia, tricuspid valve atresia,&#xD;
      hypoplastic right heart) is a life-saving drug used to ensure that the duct remains open&#xD;
      until a full, partial or temporary surgical correction or intervention is made. In the&#xD;
      antenatal period, the placenta is a good source of prostaglandins. However, with the&#xD;
      disappearance of the placental circulation after birth, many mechanisms ensure that the&#xD;
      patent ductus arteriosus closes first functional and then anatomically. Due to these&#xD;
      mechanisms occurring in the early days of life, babies who have ductus-dependent congenital&#xD;
      heart diseases show themselves with severe clinical signs and symptoms such as cyanosis and&#xD;
      circulatory disorders in this early neonatal period, when ductus begins to close when&#xD;
      diagnosis and treatment are not performed. Echocardiography should be performed by the&#xD;
      pediatric cardiology specialist as soon as possible after delivery to babies diagnosed in the&#xD;
      antenatal period, and if a ductus-dependent congenital heart disease diagnosis is confirmed,&#xD;
      PGE1 infusion should be started immediately, and the patient should be consulted with a&#xD;
      pediatric cardiovascular surgery specialist and a surgical intervention plan should be&#xD;
      provided as soon as possible.Due to these mechanisms occurring in the early days of life,&#xD;
      babies who have ductus-dependent congenital heart diseases show themselves with severe&#xD;
      clinical signs and symptoms such as cyanosis and circulatory disorders in this early neonatal&#xD;
      period, when ductus begins to close when diagnosis and treatment are not performed.&#xD;
      Echocardiography should be performed by the pediatric cardiology specialist as soon as&#xD;
      possible after delivery to babies diagnosed in the antenatal period, and if a&#xD;
      ductus-dependent congenital heart disease diagnosis is confirmed, PGE1 infusion should be&#xD;
      started immediately, and the patient should be consulted with a pediatric cardiovascular&#xD;
      surgery specialist and a surgical intervention plan should be provided as soon as possible.&#xD;
      Prostaglandin E1 infusion is given as a continuous intravenous infusion. PGE1 has some side&#xD;
      effects. The most common side effects are apnea, hyperthermia, and vasodilatation on the&#xD;
      skin, they occur around 10-14% and are usually dose-related side effects. In addition,&#xD;
      bradycardia, hypotension, convulsion, tachycardia, diarrhea, sepsis, necrotizing&#xD;
      enterocolitis, hypernatremia, hyponatremia, hypokalemia, respiratory depression, arrhythmia,&#xD;
      congestive heart failure, gastric regurgitation, bleeding, anuria, hematuria and&#xD;
      hypoglycaemia are more rare effects. The frequency and severity of these side effects usually&#xD;
      depend on the dose of the drug and the time used. Many of these side effects disappear or&#xD;
      decrease significantly when the medication is stopped or the dose is reduced. An important&#xD;
      complication that can be seen with long-term use is cortical hyperostosis in long bones.&#xD;
      Among the very rare side effects of the drug Prostaglandin E1 are hyperplasia of the gastric&#xD;
      mucosa and the development of pyloric stenosis.Hypertrophic pyloric stenosis develops as a&#xD;
      result of hypertrophy of circular pyloric muscles in the newborn period. Ultrasonography&#xD;
      (USG) is the primary diagnosis and imaging method, because it does not contain radiation, it&#xD;
      has replaced contrast studies. In ultrasonography, the thickness of the pyloric muscle from&#xD;
      the mucosa to the serosa is more than 2-3 mm and the length of the pyloric canal is over 16&#xD;
      mm. In the literature, there is no study on the effect of PGE1 increasing the pyloric wall&#xD;
      thickness in newborns, there is a case report from our hospital in this regard. In this&#xD;
      study, we aimed to evaluate the effects of the drug on pyloric wall thickness prospectively&#xD;
      with weekly ultrasonography measurements in infants given PGE1 infusion due to congenital&#xD;
      heart disease. Ultrasonography measurements will be made at the bedside (with the&#xD;
      ultrasonography device of our unit) by an experienced pediatric radiologist in pediatric&#xD;
      cases. No intervention in the treatment, medical decisions and follow-up of patients will be&#xD;
      made. Neonatal babies who were born in Hacettepe University Faculty of Medicine Ihsan&#xD;
      Dogramaci Children's Hospital Neonatal Intensive Care Unit and who were receiving&#xD;
      prostaglandin E1 infusion due to PDA-dependent congenital heart disease will be included in&#xD;
      the study. Infants who do not have consent to participate, babies with chromosomal disease&#xD;
      and hereditary metabolic disease will not be included in the study. In addition, babies who&#xD;
      have an exitus in the first week of life and whose ultrasonography measurements cannot be&#xD;
      obtained, and babies whose prostaglandin E1 infusion is discontinued by taking the second&#xD;
      ultrasonographic measurement in the first week of life will be excluded from the study.&#xD;
&#xD;
      Study Design:&#xD;
&#xD;
        -  Patients who have to receive Prostaglandin E1 treatment due to congenital heart disease&#xD;
           followed in the neonatal department of our hospital will be included in the study after&#xD;
           their consent and approval with their families without recording their identity&#xD;
           information.&#xD;
&#xD;
        -  Pyloric thicknesses will be measured by a pediatric radiologist once a week (at least&#xD;
           twice) during the period when patients use PGE1.&#xD;
&#xD;
        -  After reaching the sufficient number of cases (20 cases), increases in the pyloric wall&#xD;
           thickness dimensions will be compared with statistical analysis. The number of cases was&#xD;
           determined in accordance with the rate of hospitalization in our unit during the&#xD;
           determined period (18 months). In this way, since the studies are in the form of a case&#xD;
           report and the original article cannot be found in the literature, the observed power of&#xD;
           the study will be calculated after the study is completed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">May 6, 2019</start_date>
  <completion_date type="Anticipated">November 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2020</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>7 Days</target_duration>
  <primary_outcome>
    <measure>Effect of prostaglandin E1 treatment on pyloric wall thickness in newborn period</measure>
    <time_frame>18 months</time_frame>
    <description>It is aimed to evaluate whether there is a possible increase in pyloric wall thickness in newborn babies given Prostaglandin E1 due to any congenital heart disease.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measurement of pyloric wall thickness after discontinuation of prostaglandin E1 infusion</measure>
    <time_frame>18 months</time_frame>
    <description>The side effect of PGE1, which is increased pyloric wall thickness, is temporary. We aimed that after discontinuation of the drug, babies pyloric wall thickness will normal.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Pyloric Stenosis;Acquired</condition>
  <condition>Congenital Heart Disease</condition>
  <arm_group>
    <arm_group_label>one</arm_group_label>
    <description>there is only one patient group. This group of patients, given the same dose and at the same time, is examined by ultrasonography to determine the thickness of the pyloric muscle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prostaglandin E1</intervention_name>
    <description>The same drug will be used. In this study the same patients will be evaluated after the same dose of medication.</description>
    <arm_group_label>one</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Newborn babies between 0- 28 days.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newborn babies who are hospitalized in Hacettepe University Faculty of Medicine İhsan&#xD;
             Doğramacı Children's Hospital Neonatal Intensive Care Unit and who are receiving&#xD;
             prostaglandin E1 infusion due to PDA-dependent congenital heart disease.&#xD;
&#xD;
          -  Newborns who have the above criteria and whose consent form has been enlightened by&#xD;
             their parents has been read and accepted to participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Babies whose consent to participate in the study cannot be obtained.&#xD;
&#xD;
          -  Babies with chromosomal disease or hereditary metabolic disease&#xD;
&#xD;
          -  Babies who died during the first week of life and whose ultrasonography measurements&#xD;
             could not be obtained.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>28 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hasan T Celik, Ass Prof.</last_name>
    <role>Study Chair</role>
    <affiliation>Hacettepe University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hacettepe University</name>
      <address>
        <city>Ankara</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633330/</url>
    <description>Case report</description>
  </link>
  <link>
    <url>https://pubmed.ncbi.nlm.nih.gov/26813395/</url>
    <description>Complications of Long-Term Prostaglandin E1 Use in Newborns With Ductal-Dependent Critical Congenital Heart Disease</description>
  </link>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2020</study_first_posted>
  <last_update_submitted>July 30, 2020</last_update_submitted>
  <last_update_submitted_qc>July 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hacettepe University</investigator_affiliation>
    <investigator_full_name>H. Tolga Çelik</investigator_full_name>
    <investigator_title>associate professor</investigator_title>
  </responsible_party>
  <keyword>Congenital Heart Disease</keyword>
  <keyword>Prostaglandine E1 treatment</keyword>
  <keyword>Prostaglandine E1 Side Effects</keyword>
  <keyword>pyloric wall thickness</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pyloric Stenosis</mesh_term>
    <mesh_term>Gastric Outlet Obstruction</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Heart Defects, Congenital</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alprostadil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>At the end of the study, the results of the study will be written as an article and shared with the researchers.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 6, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT04496050/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04496050
org study id: KA-19044
nct id: NCT04496050
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Prostaglandin E1 (PGE1) has been used in the medical treatment of ductal dependent critical
      congenital heart disease in neonates. Apnea/ bradycardia, hypotension, hypokalemia, feeding
      difficulties, fever, jitteriness are the most important side effects of PGE1. Also gastric
      outlet has been reported.

      We aimed to determine effect of PGE1 treatment on pyloric wall thickness in newborn period.
      In this study, the side effect of increase of pylorus muscle wall thickness will be monitored
      with weekly ultrasonography. No intervention in the treatment, medical decisions and
      follow-up of these patients will be made. After reaching the sufficient number of cases (20
      cases), increases in the pyloric wall thickness dimensions will be compared with statistical
      analysis. The number of cases was determined in accordance with the rate of hospitalization
      in our unit during the determined period (18 months).
Intravenous prostaglandin E1 infusion is referred to as ductus dependent diseases, in
      systemic (aortic blood flow) circulation (eg critical aortic coarctation, intermittent arcus
      aorta, hypoplastic left heart, transposition of great artery), or lung blood flow through
      patent ductus arteriosus ( For example, pulmonary valve atresia, tricuspid valve atresia,
      hypoplastic right heart) is a life-saving drug used to ensure that the duct remains open
      until a full, partial or temporary surgical correction or intervention is made. In the
      antenatal period, the placenta is a good source of prostaglandins. However, with the
      disappearance of the placental circulation after birth, many mechanisms ensure that the
      patent ductus arteriosus closes first functional and then anatomically. Due to these
      mechanisms occurring in the early days of life, babies who have ductus-dependent congenital
      heart diseases show themselves with severe clinical signs and symptoms such as cyanosis and
      circulatory disorders in this early neonatal period, when ductus begins to close when
      diagnosis and treatment are not performed. Echocardiography should be performed by the
      pediatric cardiology specialist as soon as possible after delivery to babies diagnosed in the
      antenatal period, and if a ductus-dependent congenital heart disease diagnosis is confirmed,
      PGE1 infusion should be started immediately, and the patient should be consulted with a
      pediatric cardiovascular surgery specialist and a surgical intervention plan should be
      provided as soon as possible.Due to these mechanisms occurring in the early days of life,
      babies who have ductus-dependent congenital heart diseases show themselves with severe
      clinical signs and symptoms such as cyanosis and circulatory disorders in this early neonatal
      period, when ductus begins to close when diagnosis and treatment are not performed.
      Echocardiography should be performed by the pediatric cardiology specialist as soon as
      possible after delivery to babies diagnosed in the antenatal period, and if a
      ductus-dependent congenital heart disease diagnosis is confirmed, PGE1 infusion should be
      started immediately, and the patient should be consulted with a pediatric cardiovascular
      surgery specialist and a surgical intervention plan should be provided as soon as possible.
      Prostaglandin E1 infusion is given as a continuous intravenous infusion. PGE1 has some side
      effects. The most common side effects are apnea, hyperthermia, and vasodilatation on the
      skin, they occur around 10-14% and are usually dose-related side effects. In addition,
      bradycardia, hypotension, convulsion, tachycardia, diarrhea, sepsis, necrotizing
      enterocolitis, hypernatremia, hyponatremia, hypokalemia, respiratory depression, arrhythmia,
      congestive heart failure, gastric regurgitation, bleeding, anuria, hematuria and
      hypoglycaemia are more rare effects. The frequency and severity of these side effects usually
      depend on the dose of the drug and the time used. Many of these side effects disappear or
      decrease significantly when the medication is stopped or the dose is reduced. An important
      complication that can be seen with long-term use is cortical hyperostosis in long bones.
      Among the very rare side effects of the drug Prostaglandin E1 are hyperplasia of the gastric
      mucosa and the development of pyloric stenosis.Hypertrophic pyloric stenosis develops as a
      result of hypertrophy of circular pyloric muscles in the newborn period. Ultrasonography
      (USG) is the primary diagnosis and imaging method, because it does not contain radiation, it
      has replaced contrast studies. In ultrasonography, the thickness of the pyloric muscle from
      the mucosa to the serosa is more than 2-3 mm and the length of the pyloric canal is over 16
      mm. In the literature, there is no study on the effect of PGE1 increasing the pyloric wall
      thickness in newborns, there is a case report from our hospital in this regard. In this
      study, we aimed to evaluate the effects of the drug on pyloric wall thickness prospectively
      with weekly ultrasonography measurements in infants given PGE1 infusion due to congenital
      heart disease. Ultrasonography measurements will be made at the bedside (with the
      ultrasonography device of our unit) by an experienced pediatric radiologist in pediatric
      cases. No intervention in the treatment, medical decisions and follow-up of patients will be
      made. Neonatal babies who were born in Hacettepe University Faculty of Medicine Ihsan
      Dogramaci Children's Hospital Neonatal Intensive Care Unit and who were receiving
      prostaglandin E1 infusion due to PDA-dependent congenital heart disease will be included in
      the study. Infants who do not have consent to participate, babies with chromosomal disease
      and hereditary metabolic disease will not be included in the study. In addition, babies who
      have an exitus in the first week of life and whose ultrasonography measurements cannot be
      obtained, and babies whose prostaglandin E1 infusion is discontinued by taking the second
      ultrasonographic measurement in the first week of life will be excluded from the study.

      Study Design:

        -  Patients who have to receive Prostaglandin E1 treatment due to congenital heart disease
           followed in the neonatal department of our hospital will be included in the study after
           their consent and approval with their families without recording their identity
           information.

        -  Pyloric thicknesses will be measured by a pediatric radiologist once a week (at least
           twice) during the period when patients use PGE1.

        -  After reaching the sufficient number of cases (20 cases), increases in the pyloric wall
           thickness dimensions will be compared with statistical analysis. The number of cases was
           determined in accordance with the rate of hospitalization in our unit during the
           determined period (18 months). In this way, since the studies are in the form of a case
           report and the original article cannot be found in the literature, the observed power of
           the study will be calculated after the study is completed.
observational model: Case-Only
time perspective: Prospective
measure: Effect of prostaglandin E1 treatment on pyloric wall thickness in newborn period
time frame: 18 months
description: It is aimed to evaluate whether there is a possible increase in pyloric wall thickness in newborn babies given Prostaglandin E1 due to any congenital heart disease.
measure: Measurement of pyloric wall thickness after discontinuation of prostaglandin E1 infusion
time frame: 18 months
description: The side effect of PGE1, which is increased pyloric wall thickness, is temporary. We aimed that after discontinuation of the drug, babies pyloric wall thickness will normal.
arm group label: one
description: there is only one patient group. This group of patients, given the same dose and at the same time, is examined by ultrasonography to determine the thickness of the pyloric muscle.
intervention type: Drug
intervention name: Prostaglandin E1
description: The same drug will be used. In this study the same patients will be evaluated after the same dose of medication.
arm group label: one
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 28 Days
healthy volunteers: No
last name: Hasan T Celik, Ass Prof.
role: Study Chair
affiliation: Hacettepe University
facility: 
country: Turkey
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633330/
description: Case report
url: https://pubmed.ncbi.nlm.nih.gov/26813395/
description: Complications of Long-Term Prostaglandin E1 Use in Newborns With Ductal-Dependent Critical Congenital Heart Disease
responsible party type: Principal Investigator
investigator affiliation: Hacettepe University
investigator full name: H. Tolga Çelik
investigator title: associate professor
mesh term: Pyloric Stenosis
mesh term: Gastric Outlet Obstruction
mesh term: Heart Diseases
mesh term: Heart Defects, Congenital
mesh term: Alprostadil
sharing ipd: Undecided
ipd description: At the end of the study, the results of the study will be written as an article and shared with the researchers.
provided document: 