<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/NCT03782610</url>
  </required_header>
  <id_info>
    <org_study_id>1800684</org_study_id>
    <secondary_id>1R01HL145032</secondary_id>
    <nct_id>NCT03782610</nct_id>
  </id_info>
  <brief_title>Early Prediction of Spontaneous Patent Ductus Arteriosus (PDA) Closure and PDA-Associated Outcomes</brief_title>
  <official_title>Early Prediction of Spontaneous Patent Ductus Arteriosus (PDA) Closure and PDA-Associated Outcomes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nationwide Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ohio State University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>OhioHealth</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mount Carmel Health System</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nationwide Children's Hospital</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>
      Patent ductus arteriosus (PDA), very common in preterm infants, is the delayed closure of a&#xD;
      fetal blood vessel that limits blood flow through the lungs. PDA is associated with mortality&#xD;
      and harmful long term outcomes including chronic lung disease and neurodevelopmental delay.&#xD;
      Although, treatments to close PDA likely benefit some infants, widespread routine treatment&#xD;
      of all preterm infants with PDA may not improve important outcomes. Left untreated, most PDAs&#xD;
      close spontaneously. Thus, PDA treatment is increasingly controversial and varies markedly&#xD;
      between hospitals and individual providers. The relevant and still unanswered clinical&#xD;
      question is not whether to treat all preterm infants with PDA, but whom to treat and when.&#xD;
      Treatment detriments may outweigh benefits, since all forms of deliberate PDA closure have&#xD;
      potential adverse effects, especially in infants destined for early, spontaneous PDA closure.&#xD;
      Unfortunately, clinicians cannot currently predict in the 1st month which infants are at&#xD;
      highest risk for persistent PDA, and which combination of clinical risk factors,&#xD;
      echocardiographic (echo) measurements, and serum biomarkers may best predict PDA-associated&#xD;
      harm. The American Academy of Pediatrics has acknowledged early identification of infants at&#xD;
      high-risk from PDA as a key research goal for informing future PDA-treatment effectiveness&#xD;
      trials.&#xD;
&#xD;
      Our objective is to use a prospective cohort of untreated infants with PDA to predict&#xD;
      spontaneous ductal closure timing and identify echo measurements and biomarkers that are&#xD;
      present in the 1st postnatal month and associated with long-term impairment. Our central&#xD;
      hypothesis is that these risk factors can be determined to inform appropriate clinical&#xD;
      treatments when necessary. Clinical, serum and urine biomarkers (BNP, NTpBNP, NGAL, H-FABP),&#xD;
      and echo variables sequentially collected during each of the first 4 postnatal weeks will be&#xD;
      examined. In addition myocardial deformation imaging (MDI) and tissue Doppler imaging (TDI),&#xD;
      innovative echo methods, will facilitate the quantitative evaluation of myocardial&#xD;
      performance. Aim 1 will estimate the probability of spontaneous PDA closure and predict the&#xD;
      timing of ductal closure using echo, biomarker, and clinical predictors. Aim 2 will specify&#xD;
      which echo predictors and biomarkers are associated with mortality and severity of&#xD;
      respiratory illness at 36-weeks PMA. Aim 3 will identify which echo predictors and biomarkers&#xD;
      are associated with 22- to 26-month neurodevelopment. All models will be validated in a&#xD;
      separate cohort. This project will significantly contribute to clinical outcomes and PDA&#xD;
      management by reducing unnecessary and harmful overtreatment of infants with a high&#xD;
      probability of early spontaneous PDA closure, and will permit the development of&#xD;
      outcomes-focused trials to examine the effectiveness of PDA closure in those &quot;high-risk&quot;&#xD;
      infants most likely to receive benefit.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2019</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>22 Months</target_duration>
  <primary_outcome>
    <measure>Patent ductus arteriosus (PDA) closure documented via echocardiogram by 36-weeks postmenstrual age (PMA) (binary)</measure>
    <time_frame>Outcome will be documented between &lt;72-hour screening echo and 36-weeks PMA.</time_frame>
    <description>Documented closure of PDA on echocardiogram. Echocardiograms to document the primary outcome will be conducted weekly for the first four postnatal weeks and every other week thereafter, between study entry and 36-weeks PMA until PDA-closure is documented</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mortality or supplemental oxygen or positive-pressure respiratory support at 36-weeks PMA (binary)</measure>
    <time_frame>Outcome will be documented between &lt;72-hour screening echo and 36-weeks PMA</time_frame>
    <description>Death occurring between study entry at &lt;72-hours postnatal and 36-weeks PMA OR an oxygen or positive-pressure ventilation requirement at 36-weeks gestational age (=moderate bronchopulmonary dysplasia [BPD] or severe BPD)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Composite Bayley III Motor Score at 22-26 months corrected age (continuous)</measure>
    <time_frame>Bayley III Score Testing will occur at 22 to 26 months corrected age (CA) (age since birth - number of weeks born before 40-weeks gestation)</time_frame>
    <description>Composite motor score at 22 to 26-months postnatal as measured by Bayley Scales of Infant and Toddler Development- 3rd Edition (Bayley III)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality by 36-weeks PMA (binary)</measure>
    <time_frame>Death occuring between 72-hours postnatal and 36-weeks PMA</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bayley III Gross Motor Development Scaled Standard Score at 22-26 months corrected age (continuous)</measure>
    <time_frame>Recorded at 22-26 months corrected age</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bayley III Fine Motor Development Scaled Standard Score postnatal age at 22-26 months corrected age (continuous)</measure>
    <time_frame>Recorded at 22-26 months corrected age</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bayley III Cognitive Composite Score at 22-26 months corrected age (continuous)</measure>
    <time_frame>Recorded at 22-26 months corrected age</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bayley III Language Composite Score at 22-26 months corrected age (continuous)</measure>
    <time_frame>Recorded at 22-26 months corrected age</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Normal cardiac function at 36-weeks PMA (binary)</measure>
    <time_frame>Recorded at 36-weeks PMA or discharge if prior to 36-weeks</time_frame>
    <description>No functional abnormalities identified on the 36-week echocardiogram, as read by the study cardiologist</description>
  </other_outcome>
  <other_outcome>
    <measure>Quantitative myocardial deformation imaging (MDI) at 36-weeks PMA (continuous)</measure>
    <time_frame>Recorded at 36-weeks PMA or discharge if prior to 36-weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Quantitative tissue Doppler imaging (TDI) at 36-weeks PMA (continuous)</measure>
    <time_frame>Recorded at 36-weeks PMA or discharge if prior to 36-weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Pulmonary Hypertension at 36-weeks PMA (binary)</measure>
    <time_frame>Recorded at 36-weeks PMA or discharge if prior to 36-weeks</time_frame>
    <description>Pulmonary hypertension noted on the 36-week echocardiogram, as read by the study cardiologist</description>
  </other_outcome>
  <other_outcome>
    <measure>Normal left atrial size at 36-weeks PMA (binary)</measure>
    <time_frame>Recorded at 36-weeks PMA or discharge if prior to 36-weeks</time_frame>
    <description>No left atrial enlargement identified on the 36-week echocardiogram, as read by the study cardiologist</description>
  </other_outcome>
  <other_outcome>
    <measure>Normal left ventricular size at 36-weeks PMA (binary)</measure>
    <time_frame>Recorded at 36-weeks PMA or discharge if prior to 36-weeks</time_frame>
    <description>No left ventricular enlargement identified on the 36-week echocardiogram, as read by the study cardiologist</description>
  </other_outcome>
  <other_outcome>
    <measure>Normal right ventricular size at 36-weeks PMA (binary)</measure>
    <time_frame>Recorded at 36-weeks PMA or discharge if prior to 36-weeks</time_frame>
    <description>No right ventricular enlargement identified on the 36-week echocardiogram, as read by the study cardiologist</description>
  </other_outcome>
  <other_outcome>
    <measure>Oxygen Dependency (Moderate BPD) (binary)</measure>
    <time_frame>Recorded at 36-weeks PMA</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Positive-Pressure Dependency (Severe BPD) (binary)</measure>
    <time_frame>Recorded at 36-weeks PMA</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Length at 36-weeks PMA</measure>
    <time_frame>Recorded at 36-weeks PMA or discharge if prior to 36-weeks</time_frame>
    <description>Length in centimeters</description>
  </other_outcome>
  <other_outcome>
    <measure>General Movements Assessment (GMA) at 36-weeks corrected age</measure>
    <time_frame>Recorded at 36-weeks PMA</time_frame>
    <description>Prechtl's method for the qualitative assessment of general movements dysfunction</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to enteral feed initiation</measure>
    <time_frame>72 hours postnatal to 36-weeks PMA</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Time to a full enteral feed diet</measure>
    <time_frame>72 hours postnatal to 36-weeks PMA</time_frame>
    <description>Infant is weaned from intravenous fluids to a full enteral feed diet (delivery of feeds may be via an enteric tube)</description>
  </other_outcome>
  <other_outcome>
    <measure>Oral feeding status (binary)</measure>
    <time_frame>Recorded at 36-weeks PMA</time_frame>
    <description>Infant is taking all feeds by mouth (PO feeds) by 36-weeks PMA</description>
  </other_outcome>
  <other_outcome>
    <measure>Weight at 36-weeks PMA</measure>
    <time_frame>Recorded at 36-weeks PMA or discharge if prior to 36-weeks</time_frame>
    <description>Weight in grams</description>
  </other_outcome>
  <other_outcome>
    <measure>Occipitofrontal circumference (OFC) at 36-weeks PMA</measure>
    <time_frame>Recorded at 36-weeks PMA or discharge if prior to 36-weeks</time_frame>
    <description>OFC in centimeters</description>
  </other_outcome>
  <other_outcome>
    <measure>Body Mass Index (BMI) at 36-weeks PMA</measure>
    <time_frame>Recorded at 36-weeks PMA or discharge if prior to 36-weeks</time_frame>
    <description>BMI calculated by (BMI= weight in kg/length in meters squared)</description>
  </other_outcome>
  <other_outcome>
    <measure>Supplemental oxygen or positive-pressure respiratory support at 40-weeks PMA (binary)</measure>
    <time_frame>Recorded at 40-weeks PMA</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Mortality by 22-26 months corrected age</measure>
    <time_frame>Death occuring between 72-hours postnatal and 22-26 months corrected age</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Duration of ductal patency from 72-hours postnatal until 22 to 26-months corrected age follow-up</measure>
    <time_frame>72 hours postnatal until 22-26 months follow-up visit</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Supplemental oxygen support (binary) at 22-26 months corrected age</measure>
    <time_frame>Recorded at 22-26 months study follow-up visit</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Supplemental positive-pressure ventilation support (binary) at 22-26 months corrected age</measure>
    <time_frame>Recorded at 22-26 months study follow-up visit</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Weight at 22-26 months corrected age</measure>
    <time_frame>Recorded at 22-26 months study follow-up visit</time_frame>
    <description>Weight in kilograms</description>
  </other_outcome>
  <other_outcome>
    <measure>Length at 22-26 months corrected age</measure>
    <time_frame>Recorded at 22-26 months study follow-up visit</time_frame>
    <description>Length in centimeters</description>
  </other_outcome>
  <other_outcome>
    <measure>Body Mass Index (BMI) at 22-26 months corrected age</measure>
    <time_frame>Recorded at 22-26 months study follow-up visit</time_frame>
    <description>BMI calculated by (BMI= weight in kg/length in meters squared)</description>
  </other_outcome>
  <other_outcome>
    <measure>Feeding status via full oral feeding or gastric-tube (binary) at 22-26 months corrected age</measure>
    <time_frame>Recorded at 22-26 months study follow-up visit</time_frame>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">675</enrollment>
  <condition>Patent Ductus Arteriosus</condition>
  <condition>Preterm Infant</condition>
  <condition>Bronchopulmonary Dysplasia</condition>
  <condition>Neurodevelopmental Abnormality</condition>
  <arm_group>
    <arm_group_label>Primary Study Cohort</arm_group_label>
    <description>450 Infants</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Validation Cohort</arm_group_label>
    <description>225 Infants. Will allow subsequent validation of models derived from the Primary Study Cohort.</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum biomarkers: beta-natriuretic peptide (BNP); N-terminal pro-B-type natriuretic peptide&#xD;
      (NTpBNP)&#xD;
&#xD;
      Urine biomarkers: neutrophil gelatinase-associated lipocalin (NGAL); heart-fatty acid-binding&#xD;
      protein (H-FABP)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        A cohort of consecutively enrolled preterm infants born between 23- and 30-weeks gestation&#xD;
        with patent ductus arteriosus (PDA) documented on echocardiogram within 72-hours postnatal.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Born between 23-weeks + 0 days (23_0/7 wks) and 29-weeks + 6 days (29_6/7 wks)&#xD;
             gestation, inclusive&#xD;
&#xD;
          -  Admitted to a study neonatal intensive care unit (NICU) within 72-hours of birth&#xD;
&#xD;
          -  PDA noted on initial screening echo at &lt;72 postnatal hours&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Life-threatening congenital abnormalities, including congenital heart disease (other&#xD;
             than PDA or small atrial septal defects/patent foramen ovale/muscular VSD)&#xD;
&#xD;
          -  Parents have chosen to allow natural death (placed a do not resuscitate order)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>72 Hours</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jonathan L Slaughter, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nationwide Children's Hospital/The Ohio State University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Carl H Backes, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nationwide Children's Hospital/The Ohio State University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jonathan L Slaughter, MD, MPH</last_name>
    <phone>1-614-355-6643</phone>
    <email>Jonathan.Slaughter@nationwidechildrens.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Carl H Backes, MD</last_name>
    <phone>1-614-355-6729</phone>
    <email>Carl.Backes@nationwidechildrens.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Nationwide Children's Hospital Main Campus Neonatal Intensive Care Unit</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jonathan L Slaughter, MD, MPH</last_name>
      <phone>614-355-6643</phone>
      <email>jonathan.slaughter@nationwidechildrens.org</email>
    </contact>
    <contact_backup>
      <last_name>Carl H Backes, MD</last_name>
      <phone>614-355-6729</phone>
      <email>Carl.Backes@nationwidechildrens.org</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Nationwide Children's Neonatal Intensive Care Unit at The Ohio State University Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jonathan L Slaughter, MD, MPH</last_name>
      <phone>614-355-6643</phone>
      <email>jonathan.slaughter@nationwidechildrens.org</email>
    </contact>
    <contact_backup>
      <last_name>Carl H Backes, MD</last_name>
      <phone>6143556729</phone>
      <email>Carl.Backes@nationwidechildrens.org</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Nationwide Children's Neonatal Intensive Care Unit at OhioHealth Riverside Methodist Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43214</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Benjamin McDonald, MD</last_name>
      <phone>614-566-4731</phone>
      <email>Benjamin_Mcdonald@mednax.com</email>
    </contact>
    <contact_backup>
      <last_name>Carl H Backes, MD</last_name>
      <phone>6143556729</phone>
      <email>Carl.Backes@nationwidechildrens.org</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Nationwide Children's Hospital Neonatal Intensive Care Unit at OhioHealth Grant Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Apurwa Naik, MD</last_name>
      <phone>614-566-9035</phone>
      <email>Apurwa.Naik@nationwidechildrens.org</email>
    </contact>
    <contact_backup>
      <last_name>Carl H Backes, MD</last_name>
      <phone>6143556729</phone>
      <email>Carl.Backes@nationwidechildrens.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Benitz WE; Committee on Fetus and Newborn, American Academy of Pediatrics. Patent Ductus Arteriosus in Preterm Infants. Pediatrics. 2016 Jan;137(1). doi: 10.1542/peds.2015-3730. Epub 2015 Dec 15.</citation>
    <PMID>26672023</PMID>
  </reference>
  <reference>
    <citation>Slaughter JL, Reagan PB, Newman TB, Klebanoff MA. Comparative Effectiveness of Nonsteroidal Anti-inflammatory Drug Treatment vs No Treatment for Patent Ductus Arteriosus in Preterm Infants. JAMA Pediatr. 2017 Mar 6;171(3):e164354. doi: 10.1001/jamapediatrics.2016.4354. Epub 2017 Mar 6.</citation>
    <PMID>28046188</PMID>
  </reference>
  <reference>
    <citation>Pavlek LR, Slaughter JL, Berman DP, Backes CH. Catheter-based closure of the patent ductus arteriosus in lower weight infants. Semin Perinatol. 2018 Jun;42(4):262-268. doi: 10.1053/j.semperi.2018.05.009. Epub 2018 Jun 13.</citation>
    <PMID>29909074</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>September 21, 2022</last_update_submitted>
  <last_update_submitted_qc>September 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nationwide Children's Hospital</investigator_affiliation>
    <investigator_full_name>Jonathan Slaughter</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Patent Ductus Arteriosus</keyword>
  <keyword>Preterm Infant</keyword>
  <keyword>Echocardiogram</keyword>
  <keyword>Prospective Cohort</keyword>
  <keyword>Prediction Modeling</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchopulmonary Dysplasia</mesh_term>
    <mesh_term>Ductus Arteriosus, Patent</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>We welcome the opportunity to share data from our investigation. All patient identifiers will be removed from the final dataset. Following the completion and publication of our investigation, we will make the data available to other users under a data sharing agreement. We will ask under the agreement that other users will commit to using the data only for research purposes, that they will not identify individual study subjects, that they will securely store the data electronically using password protection or encryption, that they will delete or destroy the data after the completion of their investigation, and that they will acknowledge the contribution of the funding agency (NIH NHLBI) and our investigative team in collecting the original data.</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_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Data will become available after the completion of our planned investigation and publication of the results. We anticipate the completion of the investigation and publication will occur by December 2025</ipd_time_frame>
    <ipd_access_criteria>Email study co-PIs Jonathan Slaughter (Jonathan.Slaughter@nationwidechildrens.org) and Carl Backes (Carl.Backes@nationwidechildrens.org)</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 26, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/10/NCT03782610/ICF_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/NCT03782610
org study id: 1800684
secondary id: 1R01HL145032
nct id: NCT03782610
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patent ductus arteriosus (PDA), very common in preterm infants, is the delayed closure of a
      fetal blood vessel that limits blood flow through the lungs. PDA is associated with mortality
      and harmful long term outcomes including chronic lung disease and neurodevelopmental delay.
      Although, treatments to close PDA likely benefit some infants, widespread routine treatment
      of all preterm infants with PDA may not improve important outcomes. Left untreated, most PDAs
      close spontaneously. Thus, PDA treatment is increasingly controversial and varies markedly
      between hospitals and individual providers. The relevant and still unanswered clinical
      question is not whether to treat all preterm infants with PDA, but whom to treat and when.
      Treatment detriments may outweigh benefits, since all forms of deliberate PDA closure have
      potential adverse effects, especially in infants destined for early, spontaneous PDA closure.
      Unfortunately, clinicians cannot currently predict in the 1st month which infants are at
      highest risk for persistent PDA, and which combination of clinical risk factors,
      echocardiographic (echo) measurements, and serum biomarkers may best predict PDA-associated
      harm. The American Academy of Pediatrics has acknowledged early identification of infants at
      high-risk from PDA as a key research goal for informing future PDA-treatment effectiveness
      trials.

      Our objective is to use a prospective cohort of untreated infants with PDA to predict
      spontaneous ductal closure timing and identify echo measurements and biomarkers that are
      present in the 1st postnatal month and associated with long-term impairment. Our central
      hypothesis is that these risk factors can be determined to inform appropriate clinical
      treatments when necessary. Clinical, serum and urine biomarkers (BNP, NTpBNP, NGAL, H-FABP),
      and echo variables sequentially collected during each of the first 4 postnatal weeks will be
      examined. In addition myocardial deformation imaging (MDI) and tissue Doppler imaging (TDI),
      innovative echo methods, will facilitate the quantitative evaluation of myocardial
      performance. Aim 1 will estimate the probability of spontaneous PDA closure and predict the
      timing of ductal closure using echo, biomarker, and clinical predictors. Aim 2 will specify
      which echo predictors and biomarkers are associated with mortality and severity of
      respiratory illness at 36-weeks PMA. Aim 3 will identify which echo predictors and biomarkers
      are associated with 22- to 26-month neurodevelopment. All models will be validated in a
      separate cohort. This project will significantly contribute to clinical outcomes and PDA
      management by reducing unnecessary and harmful overtreatment of infants with a high
      probability of early spontaneous PDA closure, and will permit the development of
      outcomes-focused trials to examine the effectiveness of PDA closure in those "high-risk"
      infants most likely to receive benefit.
observational model: Cohort
time perspective: Prospective
measure: Patent ductus arteriosus (PDA) closure documented via echocardiogram by 36-weeks postmenstrual age (PMA) (binary)
time frame: Outcome will be documented between <72-hour screening echo and 36-weeks PMA.
description: Documented closure of PDA on echocardiogram. Echocardiograms to document the primary outcome will be conducted weekly for the first four postnatal weeks and every other week thereafter, between study entry and 36-weeks PMA until PDA-closure is documented
measure: Mortality or supplemental oxygen or positive-pressure respiratory support at 36-weeks PMA (binary)
time frame: Outcome will be documented between <72-hour screening echo and 36-weeks PMA
description: Death occurring between study entry at <72-hours postnatal and 36-weeks PMA OR an oxygen or positive-pressure ventilation requirement at 36-weeks gestational age (=moderate bronchopulmonary dysplasia [BPD] or severe BPD)
measure: Composite Bayley III Motor Score at 22-26 months corrected age (continuous)
time frame: Bayley III Score Testing will occur at 22 to 26 months corrected age (CA) (age since birth - number of weeks born before 40-weeks gestation)
description: Composite motor score at 22 to 26-months postnatal as measured by Bayley Scales of Infant and Toddler Development- 3rd Edition (Bayley III)
measure: Mortality by 36-weeks PMA (binary)
time frame: Death occuring between 72-hours postnatal and 36-weeks PMA
measure: Bayley III Gross Motor Development Scaled Standard Score at 22-26 months corrected age (continuous)
time frame: Recorded at 22-26 months corrected age
measure: Bayley III Fine Motor Development Scaled Standard Score postnatal age at 22-26 months corrected age (continuous)
time frame: Recorded at 22-26 months corrected age
measure: Bayley III Cognitive Composite Score at 22-26 months corrected age (continuous)
time frame: Recorded at 22-26 months corrected age
measure: Bayley III Language Composite Score at 22-26 months corrected age (continuous)
time frame: Recorded at 22-26 months corrected age
measure: Normal cardiac function at 36-weeks PMA (binary)
time frame: Recorded at 36-weeks PMA or discharge if prior to 36-weeks
description: No functional abnormalities identified on the 36-week echocardiogram, as read by the study cardiologist
measure: Quantitative myocardial deformation imaging (MDI) at 36-weeks PMA (continuous)
time frame: Recorded at 36-weeks PMA or discharge if prior to 36-weeks
measure: Quantitative tissue Doppler imaging (TDI) at 36-weeks PMA (continuous)
time frame: Recorded at 36-weeks PMA or discharge if prior to 36-weeks
measure: Pulmonary Hypertension at 36-weeks PMA (binary)
time frame: Recorded at 36-weeks PMA or discharge if prior to 36-weeks
description: Pulmonary hypertension noted on the 36-week echocardiogram, as read by the study cardiologist
measure: Normal left atrial size at 36-weeks PMA (binary)
time frame: Recorded at 36-weeks PMA or discharge if prior to 36-weeks
description: No left atrial enlargement identified on the 36-week echocardiogram, as read by the study cardiologist
measure: Normal left ventricular size at 36-weeks PMA (binary)
time frame: Recorded at 36-weeks PMA or discharge if prior to 36-weeks
description: No left ventricular enlargement identified on the 36-week echocardiogram, as read by the study cardiologist
measure: Normal right ventricular size at 36-weeks PMA (binary)
time frame: Recorded at 36-weeks PMA or discharge if prior to 36-weeks
description: No right ventricular enlargement identified on the 36-week echocardiogram, as read by the study cardiologist
measure: Oxygen Dependency (Moderate BPD) (binary)
time frame: Recorded at 36-weeks PMA
measure: Positive-Pressure Dependency (Severe BPD) (binary)
time frame: Recorded at 36-weeks PMA
measure: Length at 36-weeks PMA
time frame: Recorded at 36-weeks PMA or discharge if prior to 36-weeks
description: Length in centimeters
measure: General Movements Assessment (GMA) at 36-weeks corrected age
time frame: Recorded at 36-weeks PMA
description: Prechtl's method for the qualitative assessment of general movements dysfunction
measure: Time to enteral feed initiation
time frame: 72 hours postnatal to 36-weeks PMA
measure: Time to a full enteral feed diet
time frame: 72 hours postnatal to 36-weeks PMA
description: Infant is weaned from intravenous fluids to a full enteral feed diet (delivery of feeds may be via an enteric tube)
measure: Oral feeding status (binary)
time frame: Recorded at 36-weeks PMA
description: Infant is taking all feeds by mouth (PO feeds) by 36-weeks PMA
measure: Weight at 36-weeks PMA
time frame: Recorded at 36-weeks PMA or discharge if prior to 36-weeks
description: Weight in grams
measure: Occipitofrontal circumference (OFC) at 36-weeks PMA
time frame: Recorded at 36-weeks PMA or discharge if prior to 36-weeks
description: OFC in centimeters
measure: Body Mass Index (BMI) at 36-weeks PMA
time frame: Recorded at 36-weeks PMA or discharge if prior to 36-weeks
description: BMI calculated by (BMI= weight in kg/length in meters squared)
measure: Supplemental oxygen or positive-pressure respiratory support at 40-weeks PMA (binary)
time frame: Recorded at 40-weeks PMA
measure: Mortality by 22-26 months corrected age
time frame: Death occuring between 72-hours postnatal and 22-26 months corrected age
measure: Duration of ductal patency from 72-hours postnatal until 22 to 26-months corrected age follow-up
time frame: 72 hours postnatal until 22-26 months follow-up visit
measure: Supplemental oxygen support (binary) at 22-26 months corrected age
time frame: Recorded at 22-26 months study follow-up visit
measure: Supplemental positive-pressure ventilation support (binary) at 22-26 months corrected age
time frame: Recorded at 22-26 months study follow-up visit
measure: Weight at 22-26 months corrected age
time frame: Recorded at 22-26 months study follow-up visit
description: Weight in kilograms
measure: Length at 22-26 months corrected age
time frame: Recorded at 22-26 months study follow-up visit
description: Length in centimeters
measure: Body Mass Index (BMI) at 22-26 months corrected age
time frame: Recorded at 22-26 months study follow-up visit
description: BMI calculated by (BMI= weight in kg/length in meters squared)
measure: Feeding status via full oral feeding or gastric-tube (binary) at 22-26 months corrected age
time frame: Recorded at 22-26 months study follow-up visit
arm group label: Primary Study Cohort
description: 450 Infants
arm group label: Validation Cohort
description: 225 Infants. Will allow subsequent validation of models derived from the Primary Study Cohort.
Serum biomarkers: beta-natriuretic peptide (BNP); N-terminal pro-B-type natriuretic peptide
      (NTpBNP)

      Urine biomarkers: neutrophil gelatinase-associated lipocalin (NGAL); heart-fatty acid-binding
      protein (H-FABP)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 72 Hours
healthy volunteers: No
last name: Jonathan L Slaughter, MD, MPH
role: Principal Investigator
affiliation: Nationwide Children's Hospital/The Ohio State University
last name: Carl H Backes, MD
role: Principal Investigator
affiliation: Nationwide Children's Hospital/The Ohio State University
last name: Jonathan L Slaughter, MD, MPH
phone: 1-614-355-6643
email: Jonathan.Slaughter@nationwidechildrens.org
last name: Carl H Backes, MD
phone: 1-614-355-6729
email: Carl.Backes@nationwidechildrens.org
facility: 
status: Recruiting
contact: 
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status: Recruiting
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status: Recruiting
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country: United States
citation: Benitz WE; Committee on Fetus and Newborn, American Academy of Pediatrics. Patent Ductus Arteriosus in Preterm Infants. Pediatrics. 2016 Jan;137(1). doi: 10.1542/peds.2015-3730. Epub 2015 Dec 15.
PMID: 26672023
citation: Slaughter JL, Reagan PB, Newman TB, Klebanoff MA. Comparative Effectiveness of Nonsteroidal Anti-inflammatory Drug Treatment vs No Treatment for Patent Ductus Arteriosus in Preterm Infants. JAMA Pediatr. 2017 Mar 6;171(3):e164354. doi: 10.1001/jamapediatrics.2016.4354. Epub 2017 Mar 6.
PMID: 28046188
citation: Pavlek LR, Slaughter JL, Berman DP, Backes CH. Catheter-based closure of the patent ductus arteriosus in lower weight infants. Semin Perinatol. 2018 Jun;42(4):262-268. doi: 10.1053/j.semperi.2018.05.009. Epub 2018 Jun 13.
PMID: 29909074
responsible party type: Principal Investigator
investigator affiliation: Nationwide Children's Hospital
investigator full name: Jonathan Slaughter
investigator title: Principal Investigator
mesh term: Bronchopulmonary Dysplasia
mesh term: Ductus Arteriosus, Patent
sharing ipd: Yes
ipd description: We welcome the opportunity to share data from our investigation. All patient identifiers will be removed from the final dataset. Following the completion and publication of our investigation, we will make the data available to other users under a data sharing agreement. We will ask under the agreement that other users will commit to using the data only for research purposes, that they will not identify individual study subjects, that they will securely store the data electronically using password protection or encryption, that they will delete or destroy the data after the completion of their investigation, and that they will acknowledge the contribution of the funding agency (NIH NHLBI) and our investigative team in collecting the original data.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: Data will become available after the completion of our planned investigation and publication of the results. We anticipate the completion of the investigation and publication will occur by December 2025
ipd access criteria: Email study co-PIs Jonathan Slaughter (Jonathan.Slaughter@nationwidechildrens.org) and Carl Backes (Carl.Backes@nationwidechildrens.org)
provided document: 