<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/NCT04447989</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00104901</org_study_id>
    <secondary_id>1R61HL147833-01</secondary_id>
    <nct_id>NCT04447989</nct_id>
  </id_info>
  <brief_title>Safety of Sildenafil in Premature Infants With Severe Bronchopulmonary Dysplasia</brief_title>
  <acronym>SILDI-SAFE</acronym>
  <official_title>Safety of Sildenafil in Premature Infants With Severe Bronchopulmonary Dysplasia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Christoph Hornik</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>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, randomized, placebo-controlled, sequential dose-escalating,&#xD;
      double-masked, safety study of sildenafil in premature infants (inpatient in Neonatal&#xD;
      Intensive Care Units (NICUs)) with severe bronchopulmonary dysplasia (BPD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Screening/Baseline&#xD;
&#xD;
      Research staff will document informed consent from the parent/guardian for all participants&#xD;
      who satisfy eligibility criteria. The following information will be recorded in the case&#xD;
      report form (eCRF) from the clinical medical record:&#xD;
&#xD;
        1. Participant demographics, including birth weight and gestational age at birth&#xD;
&#xD;
        2. Maternal race/ethnicity&#xD;
&#xD;
        3. Medical history&#xD;
&#xD;
        4. Physical examination, including actual weight&#xD;
&#xD;
        5. All mean arterial pressure (MAP) obtained in the 24 hours before the first dose&#xD;
&#xD;
        6. Concomitant medications (within 24 hours prior to start of study drug)&#xD;
&#xD;
        7. Respiratory assessment&#xD;
&#xD;
        8. Laboratory evaluations&#xD;
&#xD;
        9. Echocardiogram: If performed per local standard of care &lt; 14 days prior to start of&#xD;
           study drug, a study-specific echocardiogram need not be repeated. If not performed per&#xD;
           local standard of care &lt; 14 days prior to start of study drug, an echocardiogram will be&#xD;
           required to confirm eligibility.&#xD;
&#xD;
       10. Cardiac catheterization reports, if performed per local standard of care &lt; 14 days prior&#xD;
           to start of study drug.&#xD;
&#xD;
       11. Adverse events following initial study-specific procedure&#xD;
&#xD;
      Treatment Period&#xD;
&#xD;
      The treatment period will include Days 1-28 or last day of study drug if early withdrawal of&#xD;
      study drug. The following information will be collected and recorded while the participant is&#xD;
      on study drug:&#xD;
&#xD;
        1. Actual weight on study Days 7 (± 1 day), 14 (± 1 day), 21 (± 1 day), and 28 (± 1 day) of&#xD;
           study drug administration&#xD;
&#xD;
        2. Date, time, amount, and route of study drug dose&#xD;
&#xD;
        3. All concomitant medications&#xD;
&#xD;
        4. MAP&#xD;
&#xD;
           A. All MAP values obtained 24 hours after the first dose of study drug regardless of&#xD;
           administration route.&#xD;
&#xD;
           B. MAP values will be obtained at a minimum at the following time points i. Prior to the&#xD;
           first dose of study drug or dose escalation: 2 hours (± 5 minutes), 1 hour (± 5&#xD;
           minutes), and 15 minutes (± 5 minutes) ii. If administration route is IV:&#xD;
&#xD;
             1. During and following the first dose of study drug or dose escalation: MAP at start&#xD;
                of infusion, every 15 minutes (± 5 minutes) during infusion, at end of infusion&#xD;
                (inclusive of flush) (± 5 minutes), at 15 and 30 minutes (± 5 minutes) after end of&#xD;
                infusion, hourly (± 15 minutes) for 4 hours, and once in the remaining 2 hours&#xD;
                prior to the next dose.&#xD;
&#xD;
             2. For subsequent IV doses, the lowest valid MAP value should be recorded daily while&#xD;
                on study drug.&#xD;
&#xD;
           iii. If the administration route is enteral:&#xD;
&#xD;
             1. During and following the first dose of study drug or dose escalation: MAP at start&#xD;
                of enteral administration, then every 15 minutes (± 5 minutes) for 90 minutes (1.5&#xD;
                hours), then every 30 minutes (± 5 minutes) for 60 minutes (1 hour), then hourly (±&#xD;
                15 minutes) for 4 hours, then once in the remaining 2 hours prior to the next dose.&#xD;
&#xD;
             2. For subsequent enteral doses, the lowest valid MAP value should be recorded daily&#xD;
                while on study drug.&#xD;
&#xD;
        5. Respiratory assessment, weekly&#xD;
&#xD;
        6. Laboratory evaluations, at least every other week&#xD;
&#xD;
        7. Echocardiograms and cardiac catheterization reports, if performed per local standard of&#xD;
           care&#xD;
&#xD;
        8. Pharmacokinetic (PK) sampling (after Day 7)&#xD;
&#xD;
        9. Adverse events&#xD;
&#xD;
      Weaning Period (Cohorts 2 and 3)&#xD;
&#xD;
      The weaning period will begin following Day 28 of study drug or, following the last day of&#xD;
      study drug if participant was withdrawn from study drug prior to Day 28 and the dose&#xD;
      escalated to ≥ 0.5 mg/kg IV or ≥ 1 mg/kg enteral.&#xD;
&#xD;
      The following information will be collected and recorded while the participant is weaning&#xD;
      from study drug:&#xD;
&#xD;
        1. Date, time, amount and route of study drug dose&#xD;
&#xD;
        2. MAP (the lowest MAP value on last day of wean should be recorded).&#xD;
&#xD;
        3. Respiratory assessment on last day of wean&#xD;
&#xD;
        4. Echocardiogram and cardiac catheterization reports, if performed per local standard of&#xD;
           care&#xD;
&#xD;
        5. Adverse events&#xD;
&#xD;
      Follow-up Period&#xD;
&#xD;
      The follow-up period will include Days 1-28 after the last study drug dose; last study drug&#xD;
      dose may occur prior to Day 28 for those participants who withdraw from study drug early; on&#xD;
      Day 28 for those participants who complete the full treatment period; or after last weaning&#xD;
      dose for those participants who require weaning. The following information will be reported&#xD;
      in electronic data capture system (EDC) at Day 1 (+ 2 days) and 14 (± 2days) of the follow-up&#xD;
      period (or days closest to and after Day 1 and 14, if &gt;1 assessment is available), except for&#xD;
      MAP, adverse events (AEs), and serious adverse events (SAEs) (which will be reported from&#xD;
      Days 1-28 post last study drug dose) and standard of care echocardiograms or cardiac&#xD;
      catheterization reports:&#xD;
&#xD;
        1. Physical examination, including actual weight&#xD;
&#xD;
        2. MAP (the lowest valid MAP value on follow-up Day 1, 14, 21, and 28 should be recorded).&#xD;
&#xD;
        3. Respiratory assessment&#xD;
&#xD;
        4. Laboratory evaluations&#xD;
&#xD;
        5. Echocardiogram on follow-up Day 1 (+2 days). If performed per local standard of care, a&#xD;
           study-specific echocardiogram need not be repeated. If not performed per local standard&#xD;
           of care on Day 1 (+2 days) of the follow-up period, an echocardiogram will need to be&#xD;
           performed.&#xD;
&#xD;
        6. Echocardiograms and cardiac catheterization reports, if performed per local standard of&#xD;
           care (during follow-up Days 1-28)&#xD;
&#xD;
        7. Adverse events and SAEs (during follow-up Days 1-28)&#xD;
&#xD;
      Final Study Assessment&#xD;
&#xD;
      Final study assessment will occur at the time of discharge or transfer. The following&#xD;
      information will be collected:&#xD;
&#xD;
        1. Physical examination, including actual weight&#xD;
&#xD;
        2. Respiratory assessment&#xD;
&#xD;
        3. Echocardiogram and cardiac catheterization reports, if performed per local standard of&#xD;
           care on the day of discharge or transfer or up to 2 days prior.&#xD;
&#xD;
        4. Global rank&#xD;
&#xD;
        5. Discharge information A. Discharge or transfer B. Death C. Duration of hospitalization&#xD;
&#xD;
        6. Record if treatment for retinopathy of prematurity (ROP) was required&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 27, 2021</start_date>
  <completion_date type="Anticipated">October 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2024</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Premature infants with severe BPD (inpatient in neonatal intensive care units) will be randomized in a dose escalating approach 3:1 (sildenafil: placebo) sequentially, into each of 3 cohorts. There will be approximately 40 randomized and dosed participants in each cohort for a total of up to 120 participants.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Study drug (sildenafil or placebo) will be prepared in the pharmacy by the unblinded pharmacist. Treatment cohort will be randomly assigned electronically and communicated to the pharmacist via the study portal. All other study staff and the patients/parents will be blinded to the treatment assignment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Safety based upon incidence of hypotension</measure>
    <time_frame>Through 28 days post last dose of study drug</time_frame>
    <description>Safety as determined by incidence of hypotension experienced by the participants through 28 days post last dose of study drug.&#xD;
Hypotension will be defined as any clinically significant low blood pressure event deemed by the treating physician to require intervention with a fluid bolus or the initiation or escalation of inotropic, vasopressor, or systemic steroid therapy with the specific intent to raise blood pressure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution</measure>
    <time_frame>Blood samples will be collected after any dose following the completion of 7 days (168 hours) of study drug administration.</time_frame>
    <description>Volume of distribution [Time Frame: 8 hr. dosing: time frame: 0-15 min, 30-60 min, 1-2 hr, 2-3 hr, 3-4 hr, 4-5 hr, within 15 min prior to next dose, and 16-24 hrs. after last dose.]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance</measure>
    <time_frame>Blood samples will be collected after any dose following the completion of 7 days (168 hours) of study drug administration.</time_frame>
    <description>Clearance [Time Frame: 8 hr. dosing: time frame: 0-15 min, 30-60 min, 1-2 hr, 2-3 hr, 3-4 hr, 4-5 hr, within 15 min prior to next dose, and 16-24 hrs. after last dose.]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life</measure>
    <time_frame>Blood samples will be collected after any dose following the completion of 7 days (168 hours) of study drug administration.</time_frame>
    <description>Half-life [Time Frame: 8 hr. dosing: time frame: 0-15 min, 30-60 min, 1-2 hr, 2-3 hr, 3-4 hr, 4-5 hr, within 15 min prior to next dose, and 16-24 hrs. after last dose.]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve</measure>
    <time_frame>Blood samples will be collected after any dose following the completion of 7 days (168 hours) of study drug administration.</time_frame>
    <description>Area Under the Curve [ Time Frame: 8 hr. dosing: time frame: 0-15 min, 30-60 min, 1-2 hr, 2-3 hr, 3-4 hr, 4-5 hr, within 15 min prior to next dose, and 16-24 hrs. after last dose.]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration</measure>
    <time_frame>Blood samples will be collected after any dose following the completion of 7 days (168 hours) of study drug administration.</time_frame>
    <description>Peak Plasma Concentration [Time Frame: 8 hr. dosing: time frame: 0-15 min, 30-60 min, 1-2 hr, 2-3 hr, 3-4 hr, 4-5 hr, within 15 min prior to next dose, and 16-24 hrs. after last dose.]</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Global rank</measure>
    <time_frame>Through study completion, 28 days after the last dose of study drug</time_frame>
    <description>Clinically significant events ranked in order of decreasing perceived severity. Each participant will receive a rank based upon the lowest ranking (worst) endpoint as defined in the statistical analysis plan that they experienced during the study.</description>
  </other_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Bronchopulmonary Dysplasia of Newborn</condition>
  <arm_group>
    <arm_group_label>Cohort 1, sildenafil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sildenafil (0.5 mg/kg IV or 1 mg/kg enteral) every 8 hours for 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1, placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (IV or enteral) every 8 hours for 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2, sildenafil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sildenafil (1 mg/kg IV or 2 mg/kg enteral) every 8 hours for 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2, placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (IV or enteral) every 8 hours for 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3, sildenafil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sildenafil (2 mg/kg IV or 4 mg/kg enteral) every 8 hours for 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3, placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (IV or enteral) every 8 hours for 28 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sildenafil</intervention_name>
    <description>Sildenafil citrate injection or powder for suspension</description>
    <arm_group_label>Cohort 1, sildenafil</arm_group_label>
    <arm_group_label>Cohort 2, sildenafil</arm_group_label>
    <arm_group_label>Cohort 3, sildenafil</arm_group_label>
    <other_name>Revatio</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>dextrose 5%</description>
    <arm_group_label>Cohort 1, placebo</arm_group_label>
    <arm_group_label>Cohort 2, placebo</arm_group_label>
    <arm_group_label>Cohort 3, placebo</arm_group_label>
    <other_name>Dextrose 5%</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Documented informed consent from parent or guardian, prior to study procedures&#xD;
&#xD;
          2. &lt; 29 weeks gestational age at birth&#xD;
&#xD;
          3. 32-44 weeks postmenstrual age&#xD;
&#xD;
          4. Receiving respiratory support at enrollment:&#xD;
&#xD;
               -  If 32 0/7-35 6/7 weeks postmenstrual age: mechanical ventilation (high frequency&#xD;
                  or conventional)&#xD;
&#xD;
               -  If 36 0/7-44 6/7 weeks postmenstrual age: mechanical ventilation (high frequency&#xD;
                  or conventional) OR continuous positive airway pressure (CPAP)&#xD;
&#xD;
        Note:&#xD;
&#xD;
          -  Criteria 3 and 4 define severe BPD for the purposes of this study&#xD;
&#xD;
          -  CPAP is defined as any of the following:&#xD;
&#xD;
               -  Nasal cannula &gt; 2 liters per minute (LPM)&#xD;
&#xD;
               -  Nasal continuous positive airway pressure (NCPAP)&#xD;
&#xD;
               -  Nasal intermittent positive pressure ventilation (NIPPV)&#xD;
&#xD;
               -  Noninvasive neurally adjusted ventilatory assist (NAVA)&#xD;
&#xD;
               -  Any other device designed to provide positive pressure through a nasal device&#xD;
                  (e.g., RAM cannula, etc.)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous enrollment and dosing in this study, protocol number (NHLBI-2019-SIL),&#xD;
             &quot;Safety of Sildenafil in Premature Infants with Severe Bronchopulmonary Dysplasia&#xD;
             (BPD)&quot;&#xD;
&#xD;
          2. Previous exposure to sildenafil within 7 days prior to randomization*&#xD;
&#xD;
          3. Previous exposure to vasopressors within 24 hours prior to randomization*&#xD;
&#xD;
          4. Previous exposure to inhaled nitric oxide within 24 hours prior to randomization*&#xD;
&#xD;
          5. Previous exposure to milrinone within 24 hours prior to randomization*&#xD;
&#xD;
          6. Evidence of pulmonary hypertension or moderate/large patent ductus arteriosus (PDA) on&#xD;
             the most recent echocardiogram performed within 14 days prior to randomization&#xD;
&#xD;
          7. Known major congenital heart defect requiring medical or surgical intervention in the&#xD;
             neonatal period&#xD;
&#xD;
          8. Known allergy to sildenafil&#xD;
&#xD;
          9. Known sickle cell disease&#xD;
&#xD;
         10. Aspartate aminotransferase (AST) &gt; 225 U/L &lt; 72 hours prior to randomization&#xD;
&#xD;
         11. Alanine aminotransferase (ALT) &gt; 150 U/L &lt; 72 hours prior to randomization&#xD;
&#xD;
         12. Any condition that would make the participant, in the opinion of the investigator,&#xD;
             unsuitable for the study.&#xD;
&#xD;
               -  Participant will be reassessed prior to dosing to reconfirm eligibility criteria.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>29 Weeks</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christoph Hornik, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke UMC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Matt Laughon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UNC</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Project Leader</last_name>
    <phone>919-668-8115</phone>
    <email>mary.bailey@duke.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Project Leader</last_name>
    <phone>919-668-8282</phone>
    <email>Jacqueline.Huvane@duke.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Arkansas Children's Research Institute</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ankita Shukla, MD</last_name>
      <phone>501-364-7097</phone>
      <email>ashukla@uams.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Rady Children's Hospital and Health Center</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jeanne Carroll, MD</last_name>
      <phone>858-966-5818</phone>
      <email>jcarroll@rchsd.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sharp Mary Birch Hospital for Women and Newborns</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92131</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Katheria Anup, MD</last_name>
      <phone>858-939-4170</phone>
      <email>anup.katheria@sharp.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Childrens National Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>John Berger III, MD</last_name>
      <phone>202-476-3724</phone>
      <email>jberger@childrensnational.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>South Miami Hospital</name>
      <address>
        <city>Coral Gables</city>
        <state>Florida</state>
        <zip>33146</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jorge Perez, MD</last_name>
      <phone>305-661-1515</phone>
      <email>jperezmd@kidzmedical.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Florida Jacksonville Shands Medical Center</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mark Hudak, MD</last_name>
      <phone>904-244-3056</phone>
      <email>mark.hudak@jax.ufl.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Wolfson Children's Hospital</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mark Hudak</last_name>
      <phone>904-244-3056</phone>
      <email>mark.hudak@jax.ufl.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Emory Children's Center</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shilpa Vyas-Read, MD</last_name>
      <phone>404-727-2401</phone>
      <email>svyasre@emory.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Lurie Children's Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611-2605</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Megan Lagoski, MD</last_name>
      <phone>312-227-4190</phone>
      <email>mlagoski@luriechildrens.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Illinois at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>De-Ann Pillers, MD</last_name>
      <phone>312-996-4185</phone>
      <email>pillersd@uic.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Kentucky Chandler Medical Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40506</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mina Hanna, MD</last_name>
      <phone>859-218-0718</phone>
      <email>mina.hanna@uky.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Louisville School of Medicine</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dan Stewart</last_name>
      <phone>502-629-5820</phone>
      <email>dan.stewart@louisville.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ochsner Baptist Medical Center</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amanda England, MD</last_name>
      <phone>504-894-2619</phone>
      <email>amanda.england@ochsner.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristen Leeman, MD</last_name>
      <phone>617-355-7909</phone>
      <email>kristen.leeman@childrens.harvard.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Childrens Mercy Hospital</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christopher Nitkin, MD</last_name>
      <email>crnitkin@cmh.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Nevada at University Medical Center</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89102</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francis Banfro, MD</last_name>
      <phone>702-383-2443</phone>
      <email>francis.banfro@umcsn.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Rochester School of Medicine Children's Hospital</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gloria Pryhuber, MD</last_name>
      <phone>585-507-8107</phone>
      <email>gloria_pryhuber@urmc.rochester.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Westchester Medical Center - New York Medical College</name>
      <address>
        <city>Valhalla</city>
        <state>New York</state>
        <zip>10595</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lance Parton, MD</last_name>
      <phone>914-493-8859</phone>
      <email>lance_parton@nymc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of NC at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jennifer Talbert</last_name>
      <phone>984-974-7865</phone>
      <email>jtalbert@med.unc.edu</email>
    </contact>
    <investigator>
      <last_name>Wesley Jackson, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>East Carolina University</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27858</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ryan Moore, MD</last_name>
      <phone>252-744-4690</phone>
      <email>moorer15@ecu.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Health Sciences</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jennifer Check, MD</last_name>
      <email>jcheck@wakehealth.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Rainbow Babies and Childrens Hospital</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stephanie Ford, MD</last_name>
      <phone>216-844-3387</phone>
      <email>stephanie.ford@uhhospitals.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Leif Nelin, MD</last_name>
      <phone>614-355-6719</phone>
      <email>leif.nelin@nationwidechildrens.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Tennessee Health Science Center</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38163</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Krishnan Ramesh, MD</last_name>
      <phone>901-448-4751</phone>
      <email>rkrishn4@uthsc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Vanderbilt Children's Hospital</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232-9544</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joern-Hendrik Weitkamp, MD</last_name>
      <phone>615-322-3476</phone>
      <email>hendrik.weitkamp@vumc.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Virginia Children's Hospital</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael McCulloch, MD</last_name>
      <phone>434-872-1143</phone>
      <email>mam3fk@virginia.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Gonzalez D, Laughon MM, Smith PB, Ge S, Ambalavanan N, Atz A, Sokol GM, Hornik CD, Stewart D, Mundakel G, Poindexter BB, Gaedigk R, Mills M, Cohen-Wolkowiez M, Martz K, Hornik CP; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Population pharmacokinetics of sildenafil in extremely premature infants. Br J Clin Pharmacol. 2019 Dec;85(12):2824-2837. doi: 10.1111/bcp.14111. Epub 2019 Dec 15.</citation>
    <PMID>31475367</PMID>
  </results_reference>
  <results_reference>
    <citation>Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, Laptook AR, Sanchez PJ, Van Meurs KP, Wyckoff M, Das A, Hale EC, Ball MB, Newman NS, Schibler K, Poindexter BB, Kennedy KA, Cotten CM, Watterberg KL, D'Angio CT, DeMauro SB, Truog WE, Devaskar U, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. JAMA. 2015 Sep 8;314(10):1039-51. doi: 10.1001/jama.2015.10244.</citation>
    <PMID>26348753</PMID>
  </results_reference>
  <results_reference>
    <citation>Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun;163(7):1723-9. doi: 10.1164/ajrccm.163.7.2011060. No abstract available.</citation>
    <PMID>11401896</PMID>
  </results_reference>
  <results_reference>
    <citation>Khemani E, McElhinney DB, Rhein L, Andrade O, Lacro RV, Thomas KC, Mullen MP. Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics. 2007 Dec;120(6):1260-9. doi: 10.1542/peds.2007-0971.</citation>
    <PMID>18055675</PMID>
  </results_reference>
  <results_reference>
    <citation>Morrow CB, McGrath-Morrow SA, Collaco JM. Predictors of length of stay for initial hospitalization in infants with bronchopulmonary dysplasia. J Perinatol. 2018 Sep;38(9):1258-1265. doi: 10.1038/s41372-018-0142-7. Epub 2018 Jun 8.</citation>
    <PMID>29880793</PMID>
  </results_reference>
  <results_reference>
    <citation>Jackson W, Hornik CP, Messina JA, Guglielmo K, Watwe A, Delancy G, Valdez A, MacArthur T, Peter-Wohl S, Smith PB, Tolia VN, Laughon MM. In-hospital outcomes of premature infants with severe bronchopulmonary dysplasia. J Perinatol. 2017 Jul;37(7):853-856. doi: 10.1038/jp.2017.49. Epub 2017 Apr 6.</citation>
    <PMID>28383537</PMID>
  </results_reference>
  <results_reference>
    <citation>Poets CF, Lorenz L. Prevention of bronchopulmonary dysplasia in extremely low gestational age neonates: current evidence. Arch Dis Child Fetal Neonatal Ed. 2018 May;103(3):F285-F291. doi: 10.1136/archdischild-2017-314264. Epub 2018 Jan 23.</citation>
    <PMID>29363502</PMID>
  </results_reference>
  <results_reference>
    <citation>Tyson JE, Wright LL, Oh W, Kennedy KA, Mele L, Ehrenkranz RA, Stoll BJ, Lemons JA, Stevenson DK, Bauer CR, Korones SB, Fanaroff AA. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 1999 Jun 24;340(25):1962-8. doi: 10.1056/NEJM199906243402505.</citation>
    <PMID>10379020</PMID>
  </results_reference>
  <results_reference>
    <citation>Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.</citation>
    <PMID>16707748</PMID>
  </results_reference>
  <results_reference>
    <citation>Doyle LW, Ehrenkranz RA, Halliday HL. Early (&lt; 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2014 May 13;(5):CD001146. doi: 10.1002/14651858.CD001146.pub4.</citation>
    <PMID>24825456</PMID>
  </results_reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>June 2, 2023</last_update_submitted>
  <last_update_submitted_qc>June 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Christoph Hornik</investigator_full_name>
    <investigator_title>Associate Professor of Pediatrics</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchopulmonary Dysplasia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sildenafil Citrate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is no plan to make IPD available to other researchers</ipd_description>
  </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/NCT04447989
org study id: Pro00104901
secondary id: 1R61HL147833-01
nct id: NCT04447989
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a multicenter, randomized, placebo-controlled, sequential dose-escalating,
      double-masked, safety study of sildenafil in premature infants (inpatient in Neonatal
      Intensive Care Units (NICUs)) with severe bronchopulmonary dysplasia (BPD).
Screening/Baseline

      Research staff will document informed consent from the parent/guardian for all participants
      who satisfy eligibility criteria. The following information will be recorded in the case
      report form (eCRF) from the clinical medical record:

        1. Participant demographics, including birth weight and gestational age at birth

        2. Maternal race/ethnicity

        3. Medical history

        4. Physical examination, including actual weight

        5. All mean arterial pressure (MAP) obtained in the 24 hours before the first dose

        6. Concomitant medications (within 24 hours prior to start of study drug)

        7. Respiratory assessment

        8. Laboratory evaluations

        9. Echocardiogram: If performed per local standard of care < 14 days prior to start of
           study drug, a study-specific echocardiogram need not be repeated. If not performed per
           local standard of care < 14 days prior to start of study drug, an echocardiogram will be
           required to confirm eligibility.

       10. Cardiac catheterization reports, if performed per local standard of care < 14 days prior
           to start of study drug.

       11. Adverse events following initial study-specific procedure

      Treatment Period

      The treatment period will include Days 1-28 or last day of study drug if early withdrawal of
      study drug. The following information will be collected and recorded while the participant is
      on study drug:

        1. Actual weight on study Days 7 (± 1 day), 14 (± 1 day), 21 (± 1 day), and 28 (± 1 day) of
           study drug administration

        2. Date, time, amount, and route of study drug dose

        3. All concomitant medications

        4. MAP

           A. All MAP values obtained 24 hours after the first dose of study drug regardless of
           administration route.

           B. MAP values will be obtained at a minimum at the following time points i. Prior to the
           first dose of study drug or dose escalation: 2 hours (± 5 minutes), 1 hour (± 5
           minutes), and 15 minutes (± 5 minutes) ii. If administration route is IV:

             1. During and following the first dose of study drug or dose escalation: MAP at start
                of infusion, every 15 minutes (± 5 minutes) during infusion, at end of infusion
                (inclusive of flush) (± 5 minutes), at 15 and 30 minutes (± 5 minutes) after end of
                infusion, hourly (± 15 minutes) for 4 hours, and once in the remaining 2 hours
                prior to the next dose.

             2. For subsequent IV doses, the lowest valid MAP value should be recorded daily while
                on study drug.

           iii. If the administration route is enteral:

             1. During and following the first dose of study drug or dose escalation: MAP at start
                of enteral administration, then every 15 minutes (± 5 minutes) for 90 minutes (1.5
                hours), then every 30 minutes (± 5 minutes) for 60 minutes (1 hour), then hourly (±
                15 minutes) for 4 hours, then once in the remaining 2 hours prior to the next dose.

             2. For subsequent enteral doses, the lowest valid MAP value should be recorded daily
                while on study drug.

        5. Respiratory assessment, weekly

        6. Laboratory evaluations, at least every other week

        7. Echocardiograms and cardiac catheterization reports, if performed per local standard of
           care

        8. Pharmacokinetic (PK) sampling (after Day 7)

        9. Adverse events

      Weaning Period (Cohorts 2 and 3)

      The weaning period will begin following Day 28 of study drug or, following the last day of
      study drug if participant was withdrawn from study drug prior to Day 28 and the dose
      escalated to ≥ 0.5 mg/kg IV or ≥ 1 mg/kg enteral.

      The following information will be collected and recorded while the participant is weaning
      from study drug:

        1. Date, time, amount and route of study drug dose

        2. MAP (the lowest MAP value on last day of wean should be recorded).

        3. Respiratory assessment on last day of wean

        4. Echocardiogram and cardiac catheterization reports, if performed per local standard of
           care

        5. Adverse events

      Follow-up Period

      The follow-up period will include Days 1-28 after the last study drug dose; last study drug
      dose may occur prior to Day 28 for those participants who withdraw from study drug early; on
      Day 28 for those participants who complete the full treatment period; or after last weaning
      dose for those participants who require weaning. The following information will be reported
      in electronic data capture system (EDC) at Day 1 (+ 2 days) and 14 (± 2days) of the follow-up
      period (or days closest to and after Day 1 and 14, if >1 assessment is available), except for
      MAP, adverse events (AEs), and serious adverse events (SAEs) (which will be reported from
      Days 1-28 post last study drug dose) and standard of care echocardiograms or cardiac
      catheterization reports:

        1. Physical examination, including actual weight

        2. MAP (the lowest valid MAP value on follow-up Day 1, 14, 21, and 28 should be recorded).

        3. Respiratory assessment

        4. Laboratory evaluations

        5. Echocardiogram on follow-up Day 1 (+2 days). If performed per local standard of care, a
           study-specific echocardiogram need not be repeated. If not performed per local standard
           of care on Day 1 (+2 days) of the follow-up period, an echocardiogram will need to be
           performed.

        6. Echocardiograms and cardiac catheterization reports, if performed per local standard of
           care (during follow-up Days 1-28)

        7. Adverse events and SAEs (during follow-up Days 1-28)

      Final Study Assessment

      Final study assessment will occur at the time of discharge or transfer. The following
      information will be collected:

        1. Physical examination, including actual weight

        2. Respiratory assessment

        3. Echocardiogram and cardiac catheterization reports, if performed per local standard of
           care on the day of discharge or transfer or up to 2 days prior.

        4. Global rank

        5. Discharge information A. Discharge or transfer B. Death C. Duration of hospitalization

        6. Record if treatment for retinopathy of prematurity (ROP) was required
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Premature infants with severe BPD (inpatient in neonatal intensive care units) will be randomized in a dose escalating approach 3:1 (sildenafil: placebo) sequentially, into each of 3 cohorts. There will be approximately 40 randomized and dosed participants in each cohort for a total of up to 120 participants.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Study drug (sildenafil or placebo) will be prepared in the pharmacy by the unblinded pharmacist. Treatment cohort will be randomly assigned electronically and communicated to the pharmacist via the study portal. All other study staff and the patients/parents will be blinded to the treatment assignment.
measure: Safety based upon incidence of hypotension
time frame: Through 28 days post last dose of study drug
description: Safety as determined by incidence of hypotension experienced by the participants through 28 days post last dose of study drug.
Hypotension will be defined as any clinically significant low blood pressure event deemed by the treating physician to require intervention with a fluid bolus or the initiation or escalation of inotropic, vasopressor, or systemic steroid therapy with the specific intent to raise blood pressure.
measure: Volume of Distribution
time frame: Blood samples will be collected after any dose following the completion of 7 days (168 hours) of study drug administration.
description: Volume of distribution [Time Frame: 8 hr. dosing: time frame: 0-15 min, 30-60 min, 1-2 hr, 2-3 hr, 3-4 hr, 4-5 hr, within 15 min prior to next dose, and 16-24 hrs. after last dose.]
measure: Clearance
time frame: Blood samples will be collected after any dose following the completion of 7 days (168 hours) of study drug administration.
description: Clearance [Time Frame: 8 hr. dosing: time frame: 0-15 min, 30-60 min, 1-2 hr, 2-3 hr, 3-4 hr, 4-5 hr, within 15 min prior to next dose, and 16-24 hrs. after last dose.]
measure: Half-life
time frame: Blood samples will be collected after any dose following the completion of 7 days (168 hours) of study drug administration.
description: Half-life [Time Frame: 8 hr. dosing: time frame: 0-15 min, 30-60 min, 1-2 hr, 2-3 hr, 3-4 hr, 4-5 hr, within 15 min prior to next dose, and 16-24 hrs. after last dose.]
measure: Area Under the Curve
time frame: Blood samples will be collected after any dose following the completion of 7 days (168 hours) of study drug administration.
description: Area Under the Curve [ Time Frame: 8 hr. dosing: time frame: 0-15 min, 30-60 min, 1-2 hr, 2-3 hr, 3-4 hr, 4-5 hr, within 15 min prior to next dose, and 16-24 hrs. after last dose.]
measure: Peak Plasma Concentration
time frame: Blood samples will be collected after any dose following the completion of 7 days (168 hours) of study drug administration.
description: Peak Plasma Concentration [Time Frame: 8 hr. dosing: time frame: 0-15 min, 30-60 min, 1-2 hr, 2-3 hr, 3-4 hr, 4-5 hr, within 15 min prior to next dose, and 16-24 hrs. after last dose.]
measure: Global rank
time frame: Through study completion, 28 days after the last dose of study drug
description: Clinically significant events ranked in order of decreasing perceived severity. Each participant will receive a rank based upon the lowest ranking (worst) endpoint as defined in the statistical analysis plan that they experienced during the study.
arm group label: Cohort 1, sildenafil
arm group type: Active Comparator
description: Sildenafil (0.5 mg/kg IV or 1 mg/kg enteral) every 8 hours for 28 days
arm group label: Cohort 1, placebo
arm group type: Placebo Comparator
description: Placebo (IV or enteral) every 8 hours for 28 days
arm group label: Cohort 2, sildenafil
arm group type: Active Comparator
description: Sildenafil (1 mg/kg IV or 2 mg/kg enteral) every 8 hours for 28 days
arm group label: Cohort 2, placebo
arm group type: Placebo Comparator
description: Placebo (IV or enteral) every 8 hours for 28 days
arm group label: Cohort 3, sildenafil
arm group type: Active Comparator
description: Sildenafil (2 mg/kg IV or 4 mg/kg enteral) every 8 hours for 28 days
arm group label: Cohort 3, placebo
arm group type: Placebo Comparator
description: Placebo (IV or enteral) every 8 hours for 28 days
intervention type: Drug
intervention name: Sildenafil
description: Sildenafil citrate injection or powder for suspension
arm group label: Cohort 1, sildenafil
arm group label: Cohort 2, sildenafil
arm group label: Cohort 3, sildenafil
other name: Revatio
intervention type: Drug
intervention name: Placebo
description: dextrose 5%
arm group label: Cohort 1, placebo
arm group label: Cohort 2, placebo
arm group label: Cohort 3, placebo
other name: Dextrose 5%
criteria: 
gender: All
minimum age: N/A
maximum age: 29 Weeks
healthy volunteers: No
last name: Christoph Hornik, MD
role: Principal Investigator
affiliation: Duke UMC
last name: Matt Laughon, MD
role: Principal Investigator
affiliation: UNC
last name: Project Leader
phone: 919-668-8115
email: mary.bailey@duke.edu
last name: Project Leader
phone: 919-668-8282
email: Jacqueline.Huvane@duke.edu
facility: 
status: Recruiting
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status: Recruiting
contact: 
country: United States
citation: Gonzalez D, Laughon MM, Smith PB, Ge S, Ambalavanan N, Atz A, Sokol GM, Hornik CD, Stewart D, Mundakel G, Poindexter BB, Gaedigk R, Mills M, Cohen-Wolkowiez M, Martz K, Hornik CP; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Population pharmacokinetics of sildenafil in extremely premature infants. Br J Clin Pharmacol. 2019 Dec;85(12):2824-2837. doi: 10.1111/bcp.14111. Epub 2019 Dec 15.
PMID: 31475367
citation: Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, Laptook AR, Sanchez PJ, Van Meurs KP, Wyckoff M, Das A, Hale EC, Ball MB, Newman NS, Schibler K, Poindexter BB, Kennedy KA, Cotten CM, Watterberg KL, D'Angio CT, DeMauro SB, Truog WE, Devaskar U, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. JAMA. 2015 Sep 8;314(10):1039-51. doi: 10.1001/jama.2015.10244.
PMID: 26348753
citation: Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun;163(7):1723-9. doi: 10.1164/ajrccm.163.7.2011060. No abstract available.
PMID: 11401896
citation: Khemani E, McElhinney DB, Rhein L, Andrade O, Lacro RV, Thomas KC, Mullen MP. Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics. 2007 Dec;120(6):1260-9. doi: 10.1542/peds.2007-0971.
PMID: 18055675
citation: Morrow CB, McGrath-Morrow SA, Collaco JM. Predictors of length of stay for initial hospitalization in infants with bronchopulmonary dysplasia. J Perinatol. 2018 Sep;38(9):1258-1265. doi: 10.1038/s41372-018-0142-7. Epub 2018 Jun 8.
PMID: 29880793
citation: Jackson W, Hornik CP, Messina JA, Guglielmo K, Watwe A, Delancy G, Valdez A, MacArthur T, Peter-Wohl S, Smith PB, Tolia VN, Laughon MM. In-hospital outcomes of premature infants with severe bronchopulmonary dysplasia. J Perinatol. 2017 Jul;37(7):853-856. doi: 10.1038/jp.2017.49. Epub 2017 Apr 6.
PMID: 28383537
citation: Poets CF, Lorenz L. Prevention of bronchopulmonary dysplasia in extremely low gestational age neonates: current evidence. Arch Dis Child Fetal Neonatal Ed. 2018 May;103(3):F285-F291. doi: 10.1136/archdischild-2017-314264. Epub 2018 Jan 23.
PMID: 29363502
citation: Tyson JE, Wright LL, Oh W, Kennedy KA, Mele L, Ehrenkranz RA, Stoll BJ, Lemons JA, Stevenson DK, Bauer CR, Korones SB, Fanaroff AA. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 1999 Jun 24;340(25):1962-8. doi: 10.1056/NEJM199906243402505.
PMID: 10379020
citation: Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.
PMID: 16707748
citation: Doyle LW, Ehrenkranz RA, Halliday HL. Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2014 May 13;(5):CD001146. doi: 10.1002/14651858.CD001146.pub4.
PMID: 24825456
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Christoph Hornik
investigator title: Associate Professor of Pediatrics
mesh term: Bronchopulmonary Dysplasia
mesh term: Sildenafil Citrate
sharing ipd: No
ipd description: There is no plan to make IPD available to other researchers