<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/NCT03229538</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00078106</org_study_id>
    <secondary_id>1U01TR001803-01</secondary_id>
    <nct_id>NCT03229538</nct_id>
  </id_info>
  <brief_title>STeroids to REduce Systemic Inflammation After Infant Heart Surgery</brief_title>
  <acronym>STRESS</acronym>
  <official_title>STeroids to REduce Systemic Inflammation After Infant Heart Surgery (STRESS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kevin Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Center for Advancing Translational Sciences (NCATS)</agency>
      <agency_class>NIH</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 study's objective is to determine the pharmacokinetics (PK)/pharmacodynamics (PD),&#xD;
      safety and efficacy of methylprednisolone in infants undergoing heart surgery with&#xD;
      cardiopulmonary bypass. This is a prospective, double blind, multi-center, placebo-controlled&#xD;
      safety and efficacy study. Blood samples will be collected from a subset of enrolled study&#xD;
      participants to evaluate multiple dose methylprednisolone PK/PD. Participants will be&#xD;
      randomized in a 1:1 fashion to intravenous methylprednisolone versus placebo. Study&#xD;
      drug/placebo will be administered 8 to 12 hours before the anticipated start time of surgery&#xD;
      and in the operating room at the time of initiation of cardiopulmonary bypass. Patients will&#xD;
      be followed for primary and secondary outcomes for the duration of their hospitalization.&#xD;
      Serious study drug-related adverse events will be collected for 7 days after the last dose of&#xD;
      study drug.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Overview:&#xD;
&#xD;
      Congenital heart diseases (CHD) are the most common birth defects, occurring in nearly 1% of&#xD;
      live births. Every year, an estimated 40,000 infants born in the U.S. suffer from CHD.&#xD;
      Despite advances in surgical management, CHD requiring neonatal surgery is associated with&#xD;
      poor outcomes; national registry data demonstrates post-operative major morbidity in 23% and&#xD;
      10% do not survive to hospital discharge.&#xD;
&#xD;
      Poor outcomes after neonatal heart surgery are often attributable to a severe systemic&#xD;
      inflammatory response to cardiopulmonary bypass (CPB). CPB is necessary for most neonatal CHD&#xD;
      surgeries. Therefore, to reduce the post-CPB inflammatory reaction, many surgeons administer&#xD;
      pre-or intra-operative steroids. Steroids have been shown to reduce inflammatory markers&#xD;
      after neonatal heart surgery. However, steroids also have potential harmful effects including&#xD;
      an increased risk of post-operative infection. The recent SIRS trial evaluated the safety and&#xD;
      efficacy of steroids after CPB in adults and demonstrated no beneficial effect of steroids&#xD;
      but increased risk of post-CPB myocardial infarction and other major adverse events.&#xD;
&#xD;
      Adult trial results cannot be reliably extrapolated to neonates because the neonatal response&#xD;
      to CPB is markedly different to that seen in adults; neonates demonstrate both a more&#xD;
      pronounced inflammatory reaction and a different post-operative complication profile. For&#xD;
      these reasons approximately 2/3rds of congenital heart surgeons continue to administer&#xD;
      perioperative steroids to neonates undergoing heart surgery. Yet this practice is not&#xD;
      evidence based as no safety/efficacy trial has ever evaluated steroids in neonates undergoing&#xD;
      heart surgery with CPB. Several smaller steroid trials (all enrolling &lt; 75 patients) have&#xD;
      focused on surrogate outcome measures, but none have provided conclusive data.&#xD;
&#xD;
      The major barrier to performing a steroid trial in neonates with CHD has been the high cost&#xD;
      associated with trial conduct for these relatively rare defects. To overcome this barrier,&#xD;
      the investigators will use a novel approach leveraging existing registry infrastructure at&#xD;
      CHD surgical sites that participate in the Society of Thoracic Surgeons Congenital Heart&#xD;
      Surgery Database (STS-CHSD). Sites participating in the STS-CHSD collect data into their&#xD;
      institutional databases using standardized case report forms so that the data can be exported&#xD;
      to the STS-CHSD. These sites already employ data coordinating specialists to capture patient&#xD;
      demographics, procedural variables, and post-operative outcomes (including a list of over 60&#xD;
      complication variables) using strict and consistent data element definitions. By leveraging&#xD;
      these site-specific resources the investigators project that the investigators can reduce&#xD;
      trial costs by &gt;75%.&#xD;
&#xD;
      Background:&#xD;
&#xD;
      Some surgeons/centers currently administer perioperative high dose (20mg to 60mg) intravenous&#xD;
      methylprednisolone before neonatal heart surgery with CPB. In a national registry study of &gt;&#xD;
      3000 neonates with data capture spanning 2004 to 2008, 62% of neonates undergoing surgery&#xD;
      with CPB received perioperative methylprednisolone while 38% did not. Of those receiving&#xD;
      methylprednisolone, 22% received methylprednisolone on both the day before, and day of&#xD;
      surgery, 12% on the day before surgery only, and 28% on the day of surgery only. Results of a&#xD;
      survey of surgeons from the Congenital Heart Surgeon's Society were similar; 28% did not&#xD;
      routinely use steroids for neonatal heart surgery. Of the 72% that did routinely use&#xD;
      steroids, ~1/3rd administered steroids pre-operatively and intra-operatively and the&#xD;
      remainder gave intra-operative steroids only.&#xD;
&#xD;
      Several previous small translationally focused clinical trials have evaluated the safety and&#xD;
      efficacy of methylprednisolone. In the largest contemporary trial, neonates scheduled for&#xD;
      cardiac surgery were prospectively randomized to receive either 2-dose (8 hours&#xD;
      preoperatively and operatively, n = 39) or single-dose (operatively, n = 37)&#xD;
      methylprednisolone at 30 mg/kg IV per dose in a prospective double-blind trial. Neonates&#xD;
      receiving pre-operative methylprednisolone therapy demonstrated significantly reduced&#xD;
      pre-operative pro-inflammatory cytokines including interleukin-6 and 8. There were no&#xD;
      differences between the two groups in post-operative pro-inflammatory markers and no&#xD;
      differences in the incidence of post-operative low cardiac output syndrome.&#xD;
      Methylprednisolone was well tolerated with no adverse drug reactions. The overall incidence&#xD;
      of post-operative infection was 13% (10/76) and 4% (3/76) received a post-operative insulin&#xD;
      infusion for hyperglycemia.&#xD;
&#xD;
      A meta-analysis evaluated six previous steroid trials in children undergoing heart surgery&#xD;
      with CPB. The combined enrollment of these six trials was 232 participants including 116&#xD;
      receiving peri-operative steroids; two of these studies used methylprednisolone at doses of&#xD;
      30mg/kg IV per dose (n=67 patients). The results of this meta-analysis demonstrated a&#xD;
      nonsignificant trend of reduced mortality in steroid-treated patients (11 [4.7%] vs 4 [1.7%]&#xD;
      patients; odds ratio, 0.41; 95% CI, 0.14-1.15; p = 0.089). Steroids had no effects on&#xD;
      mechanical ventilation time (117.4 ± 95.9 hr vs 137.3 ± 102.4 hr; p = 0.43) and ICU length of&#xD;
      stay (9.6 ± 4.6 d vs 9.9 ± 5.9 d; p = 0.8). Perioperative steroid administration reduced the&#xD;
      prevalence of renal dysfunction (13 [54.2%] vs 2 [8%] patients; odds ratio, 0.07; 95% CI,&#xD;
      0.01-0.38; p = 0.002). There were no significant differences in the adverse event profiles&#xD;
      for patients receiving steroids versus placebo.&#xD;
&#xD;
      The conclusions of the aforementioned studies, as well as several associated editorials have&#xD;
      all been that a large, randomized, controlled trial is needed to evaluate the safety and&#xD;
      efficacy of perioperative steroids for neonatal heart surgery with CPB.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      This study is a prospective, double-blind, multi-center, placebo-controlled safety and&#xD;
      efficacy study of methylprednisolone in neonates undergoing heart surgery with CPB. The study&#xD;
      will enroll up to 1500 neonates (&lt; 30 days of age) and the total study duration is expected&#xD;
      to be approximately 48 months. An ancillary PK/PD/Biomarker study will enroll subjects at&#xD;
      select centers. This study is unique in that it is designed to leverage existing registry&#xD;
      infrastructure at participating sites so as to reduce trial costs. Participants will be&#xD;
      randomized and will receive a randomization ID. This ID will also serve as a unique patient&#xD;
      identifier allowing us to crosslink datasets. Participants will then receive two doses of&#xD;
      study drug/placebo. The first dose will be administered 8 to 12 hours before anticipated&#xD;
      heart surgery and the second dose will be administered into the pump prime during&#xD;
      cardiopulmonary bypass. All study participants will then receive routine post-operative care.&#xD;
      Participating centers will enter all demographic, preoperative, operative and outcomes data&#xD;
      into their existing institutional databases for submission to the STS-CHSD as they currently&#xD;
      do. These data will be used to evaluate trial outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 18, 2017</start_date>
  <completion_date type="Actual">March 31, 2022</completion_date>
  <primary_completion_date type="Actual">March 31, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants at Each Global Rank Endpoint Based Upon Their Most-severe Outcome</measure>
    <time_frame>Until hospital discharge, up to 4 months</time_frame>
    <description>A composite mortality, major morbidity and length of stay global rank endpoint with endpoints ranked according to severity. For this endpoint, each randomized patient will be assigned a rank based upon their most-severe outcome. Rank of 91 = Post-operative length of stay &gt; 90 days, 92 = Post-op cardiac arrest, multi-system organ failure, renal failure with temporary dialysis, or prolonged ventilator support, 93 = Reoperation for bleeding, unplanned delayed sternal closure, or post-op unplanned interventional cardiac catheterization, 94 = Post-operative mechanical circulatory support or unplanned cardiac reoperation (exclusive of reoperation for bleeding), 95 = Renal failure with permanent dialysis, neurologic deficit persistent at discharge, or respiratory failure requiring tracheostomy; 96 = Heart transplant (during hospitalization); 97 = Operative mortality. Ranks 1 through 90 correspond to the post-operative length of stay in days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Mortality, Including In-hospital Mortality or Mortality After Hospital Discharge But Within 30 Days of the Last Dose of Study Drug</measure>
    <time_frame>up to 30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Death or Major Complication as Defined by an Outcome in One of the 7 Highest Global Ranking Categories</measure>
    <time_frame>Until hospital discharge, up to 4 months</time_frame>
    <description>The 7 highest global ranking categories range from 91 (postoperative length of hospital stay &gt; 90 days) to 97 (operative mortality).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With a Post-operative Length of Stay Greater Than 90 Days</measure>
    <time_frame>Until hospital discharge, up to 4 months</time_frame>
    <description>Calculated as discharge date minus surgery date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Prolonged Mechanical Ventilation (Greater Than 7 Days)</measure>
    <time_frame>Until hospital discharge, up to 4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Post-operative Low Cardiac Output Syndrome</measure>
    <time_frame>Until hospital discharge, up to 4 months</time_frame>
    <description>Based upon the STS-CHSD registry defined &quot;cardiac dysfunction resulting in low cardiac output&quot; complication variable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Occurrence of Any One or More of the Following STS-CHSD-defined Major Post-operative Infectious Complications: Postprocedural Infective Endocarditis, Pneumonia, Sepsis, Deep Wound Infection, Mediastinitis.</measure>
    <time_frame>Until hospital discharge, up to 4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Any Other Post-operative Complications From the Start of Study Drug Administration Until Hospital Discharge.</measure>
    <time_frame>Until hospital discharge, up to 4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK/PD - Time to Maximum Concentration (Tmax)</measure>
    <time_frame>Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK/PD - Maximum Concentration (Cmax)</measure>
    <time_frame>Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK/PD - Clearance (CL)</measure>
    <time_frame>Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK/PD - Volume of Distribution (Vd)</measure>
    <time_frame>Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-operative Biomarkers of the Inflammatory Response to Cardiopulmonary Bypass Including Interleukins 6 and 8</measure>
    <time_frame>Pre-2nd dose; a minimum of 2 of any of the following 5 time points (0-30 min after the start of CPB, 0-30 min after MUF, 1-2 hrs after CPB end, 4-6 hrs after CPB end, or 16-24 hrs after CPB end); and 36-48 hrs after CPB end</time_frame>
    <description>Only to be collected at select centers and in those patients whose parent/legally authorized representative have granted consent to blood draws</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1263</enrollment>
  <condition>Congenital Heart Disease in Children</condition>
  <condition>Inflammatory Response</condition>
  <arm_group>
    <arm_group_label>Methylprednisolone Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV Methylprednisolone</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>IV Isotonic Saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylprednisolone</intervention_name>
    <description>IV Steroid pre-operative and intra-operative</description>
    <arm_group_label>Methylprednisolone Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isotonic saline</intervention_name>
    <description>Isotonic saline pre-operative and intra-operative</description>
    <arm_group_label>Placebo Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 1 year at the time of surgery&#xD;
&#xD;
          -  Undergoing heart surgery with CPB as part of standard clinical care&#xD;
&#xD;
          -  Availability and willingness of the parent/legally authorized representative to&#xD;
             provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  &lt; 37 weeks adjusted gestational age at time of surgery&#xD;
&#xD;
          -  Any oral or intravenous steroid treatment within two days of surgery&#xD;
&#xD;
          -  Any patient receiving any of the following medications within 2 days of surgery:&#xD;
&#xD;
        Amphotericin B, aminoglutethimide, anticholinesterases, warfarin, P450 3A4 inducers&#xD;
        including (but not limited to) carbamazepine, phenobarbital, phenytoin, rifampin, bosentan&#xD;
        and nafcillin or P450 3A4 inhibitors including (but not limited to) clarithromycin,&#xD;
        voriconazole, itraconazole, ketoconazole, ciprofloxacin, diltiazem, fluconazole,&#xD;
        erythromycin and verapamil.&#xD;
&#xD;
          -  Infection contraindicating steroid use&#xD;
&#xD;
          -  Preoperative mechanical circulatory support or active resuscitation at the time of&#xD;
             randomization&#xD;
&#xD;
          -  Emergent surgery precluding steroid administration 8-12 hours before surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>12 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kevin Hill</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital of Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado, Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida Health - Shands Hospital</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann &amp; Robert Lurie Children's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611-2605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advocate Children's Hospital</name>
      <address>
        <city>Oak Lawn</city>
        <state>Illinois</state>
        <zip>60453</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital and Clinics of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Mercy Hospital</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Louis Children's Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital and Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morgan Stanley Children's Hospital of New York Presbyterian</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032-3702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229-3039</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-9020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine, Texas Children's Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Utah/Primary Children's Medical Center</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM360507.pdf</url>
    <description>United States Food and Drug Administration: Pediatric Study Plans: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Initial Pediatric Study Plans Guidance for Industry (Draft).</description>
  </link>
  <reference>
    <citation>Petrini J, Damus K, Johnston RB Jr. An overview of infant mortality and birth defects in the United States. Teratology. 1997 Jul-Aug;56(1-2):8-10. doi: 10.1002/(SICI)1096-9926(199707/08)56:1/23.0.CO;2-U. No abstract available.</citation>
    <PMID>9381406</PMID>
  </reference>
  <reference>
    <citation>Petrini J, Damus K, Russell R, Poschman K, Davidoff MJ, Mattison D. Contribution of birth defects to infant mortality in the United States. Teratology. 2002;66 Suppl 1:S3-6. doi: 10.1002/tera.90002.</citation>
    <PMID>12239736</PMID>
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  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 5, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <results_first_submitted>March 22, 2023</results_first_submitted>
  <results_first_submitted_qc>May 8, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">May 10, 2023</results_first_posted>
  <last_update_submitted>May 8, 2023</last_update_submitted>
  <last_update_submitted_qc>May 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Kevin Hill</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>Heart Diseases</mesh_term>
    <mesh_term>Heart Defects, Congenital</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylprednisolone</mesh_term>
    <mesh_term>Methylprednisolone Acetate</mesh_term>
    <mesh_term>Methylprednisolone Hemisuccinate</mesh_term>
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Prednisolone acetate</mesh_term>
    <mesh_term>Prednisolone hemisuccinate</mesh_term>
    <mesh_term>Prednisolone phosphate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The investigators will disseminate findings through publications, national presentations, participation in the CTSA Consortium, the CTSA website and via the existing infrastructure of the Society of Thoracic Surgeons Congenital Heart Surgery Database. Data collection supported by CTSA funds will follow the principles outlined in the Final NIH Statement on Sharing Research Data. Participating institutions will honor the principle that data sharing is critical for expeditious translation of research findings to the improvement of human health. The investigators abide strictly by the provisions of the Health Insurance Portability and Accountability Act (HIPAA). The investigators will continue to use traditional venues for data sharing, such as publications in leading scientific journals and deposit all applicable NIH-funded research results to PubMed Central in compliance with the NIH's Public Access Policy.</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>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 27, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/38/NCT03229538/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>1263 patients consented and randomized; 63 did not receive study drug and are excluded from final analysis.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Methylprednisolone Arm</title>
          <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative&#xD;
Study drug will be administered 8 to 12 hours before the anticipated start time of surgery and in the operating room at the time of initiation of cardiopulmonary bypass.</description>
        </group>
        <group group_id="P2">
          <title>Placebo Arm</title>
          <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative&#xD;
Placebo will be administered 8 to 12 hours before the anticipated start time of surgery and in the operating room at the time of initiation of cardiopulmonary bypass.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="599"/>
                <participants group_id="P2" count="601"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="599"/>
                <participants group_id="P2" count="601"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Methylprednisolone Arm</title>
          <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
        </group>
        <group group_id="B2">
          <title>Placebo Arm</title>
          <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="599"/>
            <count group_id="B2" value="601"/>
            <count group_id="B3" value="1200"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="599"/>
                    <count group_id="B2" value="601"/>
                    <count group_id="B3" value="1200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="126" lower_limit="14" upper_limit="191"/>
                    <measurement group_id="B2" value="124" lower_limit="14" upper_limit="182"/>
                    <measurement group_id="B3" value="125" lower_limit="14" upper_limit="187"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="599"/>
                    <count group_id="B2" value="601"/>
                    <count group_id="B3" value="1200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="279"/>
                    <measurement group_id="B2" value="267"/>
                    <measurement group_id="B3" value="546"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="320"/>
                    <measurement group_id="B2" value="334"/>
                    <measurement group_id="B3" value="654"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="599"/>
                    <count group_id="B2" value="601"/>
                    <count group_id="B3" value="1200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="80"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="143"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="519"/>
                    <measurement group_id="B2" value="538"/>
                    <measurement group_id="B3" value="1057"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>Data not collected on 32 participants.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="585"/>
                    <count group_id="B2" value="583"/>
                    <count group_id="B3" value="1168"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="90"/>
                    <measurement group_id="B2" value="102"/>
                    <measurement group_id="B3" value="192"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="428"/>
                    <measurement group_id="B2" value="425"/>
                    <measurement group_id="B3" value="853"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="599"/>
                    <count group_id="B2" value="601"/>
                    <count group_id="B3" value="1200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="599"/>
                    <measurement group_id="B2" value="601"/>
                    <measurement group_id="B3" value="1200"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants at Each Global Rank Endpoint Based Upon Their Most-severe Outcome</title>
        <description>A composite mortality, major morbidity and length of stay global rank endpoint with endpoints ranked according to severity. For this endpoint, each randomized patient will be assigned a rank based upon their most-severe outcome. Rank of 91 = Post-operative length of stay &gt; 90 days, 92 = Post-op cardiac arrest, multi-system organ failure, renal failure with temporary dialysis, or prolonged ventilator support, 93 = Reoperation for bleeding, unplanned delayed sternal closure, or post-op unplanned interventional cardiac catheterization, 94 = Post-operative mechanical circulatory support or unplanned cardiac reoperation (exclusive of reoperation for bleeding), 95 = Renal failure with permanent dialysis, neurologic deficit persistent at discharge, or respiratory failure requiring tracheostomy; 96 = Heart transplant (during hospitalization); 97 = Operative mortality. Ranks 1 through 90 correspond to the post-operative length of stay in days.</description>
        <time_frame>Until hospital discharge, up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants at Each Global Rank Endpoint Based Upon Their Most-severe Outcome</title>
          <description>A composite mortality, major morbidity and length of stay global rank endpoint with endpoints ranked according to severity. For this endpoint, each randomized patient will be assigned a rank based upon their most-severe outcome. Rank of 91 = Post-operative length of stay &gt; 90 days, 92 = Post-op cardiac arrest, multi-system organ failure, renal failure with temporary dialysis, or prolonged ventilator support, 93 = Reoperation for bleeding, unplanned delayed sternal closure, or post-op unplanned interventional cardiac catheterization, 94 = Post-operative mechanical circulatory support or unplanned cardiac reoperation (exclusive of reoperation for bleeding), 95 = Renal failure with permanent dialysis, neurologic deficit persistent at discharge, or respiratory failure requiring tracheostomy; 96 = Heart transplant (during hospitalization); 97 = Operative mortality. Ranks 1 through 90 correspond to the post-operative length of stay in days.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="599"/>
                <count group_id="O2" value="601"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Rank = 97</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 96</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 95</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 94</title>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 93</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 92</title>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 91</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 81-90</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 71-80</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 61-70</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 51-60</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 41-50</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 31-40</title>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 21-30</title>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 11-20</title>
                  <measurement_list>
                    <measurement group_id="O1" value="115"/>
                    <measurement group_id="O2" value="112"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rank = 0-10</title>
                  <measurement_list>
                    <measurement group_id="O1" value="310"/>
                    <measurement group_id="O2" value="287"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.14</p_value>
            <method>Regression, Logistic</method>
            <param_type>Adjusted Odds Ratio</param_type>
            <param_value>0.86</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.71</ci_lower_limit>
            <ci_upper_limit>1.05</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Rank = 97</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Percent Difference</param_type>
            <param_value>-0.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.6</ci_lower_limit>
            <ci_upper_limit>0.9</ci_upper_limit>
            <estimate_desc>Difference = Methylprednisolone - Placebo</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Rank &gt; or = 96</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Percent Difference</param_type>
            <param_value>-1.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.5</ci_lower_limit>
            <ci_upper_limit>0.5</ci_upper_limit>
            <estimate_desc>Difference = Methylprednisolone - Placebo</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Rank &gt; or = 95</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Percent Difference</param_type>
            <param_value>-2.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.4</ci_lower_limit>
            <ci_upper_limit>0.1</ci_upper_limit>
            <estimate_desc>Difference = Methylprednisolone - Placebo</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Rank &gt; or = 94</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Percent Difference</param_type>
            <param_value>-0.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.3</ci_lower_limit>
            <ci_upper_limit>2.7</ci_upper_limit>
            <estimate_desc>Difference = Methylprednisolone - Placebo</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Rank &gt; or = 93</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Percent Difference</param_type>
            <param_value>-3.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.8</ci_lower_limit>
            <ci_upper_limit>0.2</ci_upper_limit>
            <estimate_desc>Difference = Methylprednisolone - Placebo</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Rank &gt; or = 92</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Percent Difference</param_type>
            <param_value>-3.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.8</ci_lower_limit>
            <ci_upper_limit>0.9</ci_upper_limit>
            <estimate_desc>Difference = Methylprednisolone - Placebo</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Rank &gt; or = 91</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Percent Difference</param_type>
            <param_value>-3.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.5</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
            <estimate_desc>Difference = Methylprednisolone - Placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Mortality, Including In-hospital Mortality or Mortality After Hospital Discharge But Within 30 Days of the Last Dose of Study Drug</title>
        <time_frame>up to 30 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Mortality, Including In-hospital Mortality or Mortality After Hospital Discharge But Within 30 Days of the Last Dose of Study Drug</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="599"/>
                <count group_id="O2" value="601"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>It was estimated that 1200 patients (600 per trial group) would provide the trial with more than 90% power to detect superiority of methylprednisolone.</non_inferiority_desc>
            <p_value>0.428</p_value>
            <method>Regression, Logistic</method>
            <param_type>Adjusted Odds Ratio</param_type>
            <param_value>0.74</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.34</ci_lower_limit>
            <ci_upper_limit>1.57</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Death or Major Complication as Defined by an Outcome in One of the 7 Highest Global Ranking Categories</title>
        <description>The 7 highest global ranking categories range from 91 (postoperative length of hospital stay &gt; 90 days) to 97 (operative mortality).</description>
        <time_frame>Until hospital discharge, up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Death or Major Complication as Defined by an Outcome in One of the 7 Highest Global Ranking Categories</title>
          <description>The 7 highest global ranking categories range from 91 (postoperative length of hospital stay &gt; 90 days) to 97 (operative mortality).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="599"/>
                <count group_id="O2" value="601"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="103"/>
                    <measurement group_id="O2" value="122"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>It was estimated that 1200 patients (600 per trial group) would provide the trial with more than 90% power to detect superiority of methylprednisolone.</non_inferiority_desc>
            <p_value>0.228</p_value>
            <method>Regression, Logistic</method>
            <param_type>Adjusted Odds Ratio</param_type>
            <param_value>0.83</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.61</ci_lower_limit>
            <ci_upper_limit>1.13</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With a Post-operative Length of Stay Greater Than 90 Days</title>
        <description>Calculated as discharge date minus surgery date.</description>
        <time_frame>Until hospital discharge, up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Post-operative Length of Stay Greater Than 90 Days</title>
          <description>Calculated as discharge date minus surgery date.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="599"/>
                <count group_id="O2" value="601"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>It was estimated that 1200 patients (600 per trial group) would provide the trial with more than 90% power to detect superiority of methylprednisolone over placebo.</non_inferiority_desc>
            <param_type>Percent Difference</param_type>
            <param_value>-1.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.0</ci_lower_limit>
            <ci_upper_limit>0.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Prolonged Mechanical Ventilation (Greater Than 7 Days)</title>
        <time_frame>Until hospital discharge, up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Prolonged Mechanical Ventilation (Greater Than 7 Days)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="599"/>
                <count group_id="O2" value="601"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41"/>
                    <measurement group_id="O2" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>It was estimated that 1200 patients (600 per trial group) would provide the trial with more than 90% power to detect superiority of methylprednisolone over placebo.</non_inferiority_desc>
            <p_value>0.309</p_value>
            <method>Regression, Logistic</method>
            <param_type>Adjusted Odds Ratio</param_type>
            <param_value>0.79</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.50</ci_lower_limit>
            <ci_upper_limit>1.25</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Post-operative Low Cardiac Output Syndrome</title>
        <description>Based upon the STS-CHSD registry defined &quot;cardiac dysfunction resulting in low cardiac output&quot; complication variable.</description>
        <time_frame>Until hospital discharge, up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Post-operative Low Cardiac Output Syndrome</title>
          <description>Based upon the STS-CHSD registry defined &quot;cardiac dysfunction resulting in low cardiac output&quot; complication variable.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="599"/>
                <count group_id="O2" value="601"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>It was estimated that 1200 patients (600 per trial group) would provide the trial with more than 90% power to detect superiority of methylprednisolone over placebo.</non_inferiority_desc>
            <p_value>0.723</p_value>
            <method>Regression, Logistic</method>
            <param_type>Adjusted Odds Ratio</param_type>
            <param_value>0.91</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.52</ci_lower_limit>
            <ci_upper_limit>1.57</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Occurrence of Any One or More of the Following STS-CHSD-defined Major Post-operative Infectious Complications: Postprocedural Infective Endocarditis, Pneumonia, Sepsis, Deep Wound Infection, Mediastinitis.</title>
        <time_frame>Until hospital discharge, up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Occurrence of Any One or More of the Following STS-CHSD-defined Major Post-operative Infectious Complications: Postprocedural Infective Endocarditis, Pneumonia, Sepsis, Deep Wound Infection, Mediastinitis.</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="599"/>
                <count group_id="O2" value="601"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Any Other Post-operative Complications From the Start of Study Drug Administration Until Hospital Discharge.</title>
        <time_frame>Until hospital discharge, up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Any Other Post-operative Complications From the Start of Study Drug Administration Until Hospital Discharge.</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="599"/>
                <count group_id="O2" value="601"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="237"/>
                    <measurement group_id="O2" value="264"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.256</p_value>
            <method>Regression, Logistic</method>
            <param_type>Adjusted Odds Ratio</param_type>
            <param_value>0.86</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.67</ci_lower_limit>
            <ci_upper_limit>1.11</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK/PD - Time to Maximum Concentration (Tmax)</title>
        <time_frame>Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB)</time_frame>
        <population>Data not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>PK/PD - Time to Maximum Concentration (Tmax)</title>
          <population>Data not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK/PD - Maximum Concentration (Cmax)</title>
        <time_frame>Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB)</time_frame>
        <population>Data not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>PK/PD - Maximum Concentration (Cmax)</title>
          <population>Data not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK/PD - Clearance (CL)</title>
        <time_frame>Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB)</time_frame>
        <population>Data not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>PK/PD - Clearance (CL)</title>
          <population>Data not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK/PD - Volume of Distribution (Vd)</title>
        <time_frame>Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB)</time_frame>
        <population>Data not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>PK/PD - Volume of Distribution (Vd)</title>
          <population>Data not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Post-operative Biomarkers of the Inflammatory Response to Cardiopulmonary Bypass Including Interleukins 6 and 8</title>
        <description>Only to be collected at select centers and in those patients whose parent/legally authorized representative have granted consent to blood draws</description>
        <time_frame>Pre-2nd dose; a minimum of 2 of any of the following 5 time points (0-30 min after the start of CPB, 0-30 min after MUF, 1-2 hrs after CPB end, 4-6 hrs after CPB end, or 16-24 hrs after CPB end); and 36-48 hrs after CPB end</time_frame>
        <population>Data not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Methylprednisolone Arm</title>
            <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
          </group>
        </group_list>
        <measure>
          <title>Post-operative Biomarkers of the Inflammatory Response to Cardiopulmonary Bypass Including Interleukins 6 and 8</title>
          <description>Only to be collected at select centers and in those patients whose parent/legally authorized representative have granted consent to blood draws</description>
          <population>Data not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Until hospital discharge, up to 4 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Methylprednisolone Arm</title>
          <description>IV Methylprednisolone&#xD;
Methylprednisolone: IV Steroid pre-operative and intra-operative</description>
        </group>
        <group group_id="E2">
          <title>Placebo Arm</title>
          <description>IV Isotonic Saline&#xD;
Isotonic saline: Isotonic saline pre-operative and intra-operative</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac dysfunction</sub_title>
                <description>Study drug-related.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Enterovirus infection</sub_title>
                <description>Study drug-related.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Rhinovirus infection</sub_title>
                <description>Study drug-related.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <description>Study drug-related.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="155" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="176" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="155" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="176" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Cardiac dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="133" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="135" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Cardiac Arrest</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Intracardiac thrombus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Mediastinitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Postoperative thoracic procedure complication</sub_title>
                <counts group_id="E1" subjects_affected="125" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="135" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Procedural complication</sub_title>
                <counts group_id="E1" subjects_affected="41" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Wound dehiscence</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Subdural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Anaesthetic complication</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Catheterization cardiac</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Nervous system disorder</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Intraventricular haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="74" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="83" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Chylothorax</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Pulmonary hypertension</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Diaphragmatic paralysis</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Pulmonary hypertensive crisis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Pulmonary thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Vocal cord dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Cardiac operation</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Ventricular assist device insertion</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Hospitalization</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Cardiac pacemaker insertion</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Venous occlusion</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="601"/>
              </event>
              <event>
                <sub_title>Deep vein thrombsis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="599"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="601"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Kevin Hill, MD</name_or_title>
      <organization>Duke University</organization>
      <phone>919-681-6846</phone>
      <email>kevin.hill@duke.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03229538
org study id: Pro00078106
secondary id: 1U01TR001803-01
nct id: NCT03229538
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study's objective is to determine the pharmacokinetics (PK)/pharmacodynamics (PD),
      safety and efficacy of methylprednisolone in infants undergoing heart surgery with
      cardiopulmonary bypass. This is a prospective, double blind, multi-center, placebo-controlled
      safety and efficacy study. Blood samples will be collected from a subset of enrolled study
      participants to evaluate multiple dose methylprednisolone PK/PD. Participants will be
      randomized in a 1:1 fashion to intravenous methylprednisolone versus placebo. Study
      drug/placebo will be administered 8 to 12 hours before the anticipated start time of surgery
      and in the operating room at the time of initiation of cardiopulmonary bypass. Patients will
      be followed for primary and secondary outcomes for the duration of their hospitalization.
      Serious study drug-related adverse events will be collected for 7 days after the last dose of
      study drug.
Overview:

      Congenital heart diseases (CHD) are the most common birth defects, occurring in nearly 1% of
      live births. Every year, an estimated 40,000 infants born in the U.S. suffer from CHD.
      Despite advances in surgical management, CHD requiring neonatal surgery is associated with
      poor outcomes; national registry data demonstrates post-operative major morbidity in 23% and
      10% do not survive to hospital discharge.

      Poor outcomes after neonatal heart surgery are often attributable to a severe systemic
      inflammatory response to cardiopulmonary bypass (CPB). CPB is necessary for most neonatal CHD
      surgeries. Therefore, to reduce the post-CPB inflammatory reaction, many surgeons administer
      pre-or intra-operative steroids. Steroids have been shown to reduce inflammatory markers
      after neonatal heart surgery. However, steroids also have potential harmful effects including
      an increased risk of post-operative infection. The recent SIRS trial evaluated the safety and
      efficacy of steroids after CPB in adults and demonstrated no beneficial effect of steroids
      but increased risk of post-CPB myocardial infarction and other major adverse events.

      Adult trial results cannot be reliably extrapolated to neonates because the neonatal response
      to CPB is markedly different to that seen in adults; neonates demonstrate both a more
      pronounced inflammatory reaction and a different post-operative complication profile. For
      these reasons approximately 2/3rds of congenital heart surgeons continue to administer
      perioperative steroids to neonates undergoing heart surgery. Yet this practice is not
      evidence based as no safety/efficacy trial has ever evaluated steroids in neonates undergoing
      heart surgery with CPB. Several smaller steroid trials (all enrolling < 75 patients) have
      focused on surrogate outcome measures, but none have provided conclusive data.

      The major barrier to performing a steroid trial in neonates with CHD has been the high cost
      associated with trial conduct for these relatively rare defects. To overcome this barrier,
      the investigators will use a novel approach leveraging existing registry infrastructure at
      CHD surgical sites that participate in the Society of Thoracic Surgeons Congenital Heart
      Surgery Database (STS-CHSD). Sites participating in the STS-CHSD collect data into their
      institutional databases using standardized case report forms so that the data can be exported
      to the STS-CHSD. These sites already employ data coordinating specialists to capture patient
      demographics, procedural variables, and post-operative outcomes (including a list of over 60
      complication variables) using strict and consistent data element definitions. By leveraging
      these site-specific resources the investigators project that the investigators can reduce
      trial costs by >75%.

      Background:

      Some surgeons/centers currently administer perioperative high dose (20mg to 60mg) intravenous
      methylprednisolone before neonatal heart surgery with CPB. In a national registry study of >
      3000 neonates with data capture spanning 2004 to 2008, 62% of neonates undergoing surgery
      with CPB received perioperative methylprednisolone while 38% did not. Of those receiving
      methylprednisolone, 22% received methylprednisolone on both the day before, and day of
      surgery, 12% on the day before surgery only, and 28% on the day of surgery only. Results of a
      survey of surgeons from the Congenital Heart Surgeon's Society were similar; 28% did not
      routinely use steroids for neonatal heart surgery. Of the 72% that did routinely use
      steroids, ~1/3rd administered steroids pre-operatively and intra-operatively and the
      remainder gave intra-operative steroids only.

      Several previous small translationally focused clinical trials have evaluated the safety and
      efficacy of methylprednisolone. In the largest contemporary trial, neonates scheduled for
      cardiac surgery were prospectively randomized to receive either 2-dose (8 hours
      preoperatively and operatively, n = 39) or single-dose (operatively, n = 37)
      methylprednisolone at 30 mg/kg IV per dose in a prospective double-blind trial. Neonates
      receiving pre-operative methylprednisolone therapy demonstrated significantly reduced
      pre-operative pro-inflammatory cytokines including interleukin-6 and 8. There were no
      differences between the two groups in post-operative pro-inflammatory markers and no
      differences in the incidence of post-operative low cardiac output syndrome.
      Methylprednisolone was well tolerated with no adverse drug reactions. The overall incidence
      of post-operative infection was 13% (10/76) and 4% (3/76) received a post-operative insulin
      infusion for hyperglycemia.

      A meta-analysis evaluated six previous steroid trials in children undergoing heart surgery
      with CPB. The combined enrollment of these six trials was 232 participants including 116
      receiving peri-operative steroids; two of these studies used methylprednisolone at doses of
      30mg/kg IV per dose (n=67 patients). The results of this meta-analysis demonstrated a
      nonsignificant trend of reduced mortality in steroid-treated patients (11 [4.7%] vs 4 [1.7%]
      patients; odds ratio, 0.41; 95% CI, 0.14-1.15; p = 0.089). Steroids had no effects on
      mechanical ventilation time (117.4 ± 95.9 hr vs 137.3 ± 102.4 hr; p = 0.43) and ICU length of
      stay (9.6 ± 4.6 d vs 9.9 ± 5.9 d; p = 0.8). Perioperative steroid administration reduced the
      prevalence of renal dysfunction (13 [54.2%] vs 2 [8%] patients; odds ratio, 0.07; 95% CI,
      0.01-0.38; p = 0.002). There were no significant differences in the adverse event profiles
      for patients receiving steroids versus placebo.

      The conclusions of the aforementioned studies, as well as several associated editorials have
      all been that a large, randomized, controlled trial is needed to evaluate the safety and
      efficacy of perioperative steroids for neonatal heart surgery with CPB.

      Design:

      This study is a prospective, double-blind, multi-center, placebo-controlled safety and
      efficacy study of methylprednisolone in neonates undergoing heart surgery with CPB. The study
      will enroll up to 1500 neonates (< 30 days of age) and the total study duration is expected
      to be approximately 48 months. An ancillary PK/PD/Biomarker study will enroll subjects at
      select centers. This study is unique in that it is designed to leverage existing registry
      infrastructure at participating sites so as to reduce trial costs. Participants will be
      randomized and will receive a randomization ID. This ID will also serve as a unique patient
      identifier allowing us to crosslink datasets. Participants will then receive two doses of
      study drug/placebo. The first dose will be administered 8 to 12 hours before anticipated
      heart surgery and the second dose will be administered into the pump prime during
      cardiopulmonary bypass. All study participants will then receive routine post-operative care.
      Participating centers will enter all demographic, preoperative, operative and outcomes data
      into their existing institutional databases for submission to the STS-CHSD as they currently
      do. These data will be used to evaluate trial outcomes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants at Each Global Rank Endpoint Based Upon Their Most-severe Outcome
time frame: Until hospital discharge, up to 4 months
description: A composite mortality, major morbidity and length of stay global rank endpoint with endpoints ranked according to severity. For this endpoint, each randomized patient will be assigned a rank based upon their most-severe outcome. Rank of 91 = Post-operative length of stay > 90 days, 92 = Post-op cardiac arrest, multi-system organ failure, renal failure with temporary dialysis, or prolonged ventilator support, 93 = Reoperation for bleeding, unplanned delayed sternal closure, or post-op unplanned interventional cardiac catheterization, 94 = Post-operative mechanical circulatory support or unplanned cardiac reoperation (exclusive of reoperation for bleeding), 95 = Renal failure with permanent dialysis, neurologic deficit persistent at discharge, or respiratory failure requiring tracheostomy; 96 = Heart transplant (during hospitalization); 97 = Operative mortality. Ranks 1 through 90 correspond to the post-operative length of stay in days.
measure: Number of Participants With Mortality, Including In-hospital Mortality or Mortality After Hospital Discharge But Within 30 Days of the Last Dose of Study Drug
time frame: up to 30 days
measure: Number of Participants With Death or Major Complication as Defined by an Outcome in One of the 7 Highest Global Ranking Categories
time frame: Until hospital discharge, up to 4 months
description: The 7 highest global ranking categories range from 91 (postoperative length of hospital stay > 90 days) to 97 (operative mortality).
measure: Number of Participants With a Post-operative Length of Stay Greater Than 90 Days
time frame: Until hospital discharge, up to 4 months
description: Calculated as discharge date minus surgery date.
measure: Number of Participants With Prolonged Mechanical Ventilation (Greater Than 7 Days)
time frame: Until hospital discharge, up to 4 months
measure: Number of Participants With Post-operative Low Cardiac Output Syndrome
time frame: Until hospital discharge, up to 4 months
description: Based upon the STS-CHSD registry defined "cardiac dysfunction resulting in low cardiac output" complication variable.
measure: Number of Participants With Occurrence of Any One or More of the Following STS-CHSD-defined Major Post-operative Infectious Complications: Postprocedural Infective Endocarditis, Pneumonia, Sepsis, Deep Wound Infection, Mediastinitis.
time frame: Until hospital discharge, up to 4 months
measure: Number of Participants With Any Other Post-operative Complications From the Start of Study Drug Administration Until Hospital Discharge.
time frame: Until hospital discharge, up to 4 months
measure: PK/PD - Time to Maximum Concentration (Tmax)
time frame: Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB)
measure: PK/PD - Maximum Concentration (Cmax)
time frame: Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB)
measure: PK/PD - Clearance (CL)
time frame: Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB)
measure: PK/PD - Volume of Distribution (Vd)
time frame: Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB)
measure: Post-operative Biomarkers of the Inflammatory Response to Cardiopulmonary Bypass Including Interleukins 6 and 8
time frame: Pre-2nd dose; a minimum of 2 of any of the following 5 time points (0-30 min after the start of CPB, 0-30 min after MUF, 1-2 hrs after CPB end, 4-6 hrs after CPB end, or 16-24 hrs after CPB end); and 36-48 hrs after CPB end
description: Only to be collected at select centers and in those patients whose parent/legally authorized representative have granted consent to blood draws
arm group label: Methylprednisolone Arm
arm group type: Experimental
description: IV Methylprednisolone
arm group label: Placebo Arm
arm group type: Placebo Comparator
description: IV Isotonic Saline
intervention type: Drug
intervention name: Methylprednisolone
description: IV Steroid pre-operative and intra-operative
arm group label: Methylprednisolone Arm
intervention type: Drug
intervention name: Isotonic saline
description: Isotonic saline pre-operative and intra-operative
arm group label: Placebo Arm
criteria: 
gender: All
minimum age: N/A
maximum age: 12 Months
healthy volunteers: No
last name: Kevin Hill
role: Principal Investigator
affiliation: Duke University
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country: United States
url: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM360507.pdf
description: United States Food and Drug Administration: Pediatric Study Plans: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Initial Pediatric Study Plans Guidance for Industry (Draft).
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PMID: 9381406
citation: Petrini J, Damus K, Russell R, Poschman K, Davidoff MJ, Mattison D. Contribution of birth defects to infant mortality in the United States. Teratology. 2002;66 Suppl 1:S3-6. doi: 10.1002/tera.90002.
PMID: 12239736
citation: Yang Q, Chen H, Correa A, Devine O, Mathews TJ, Honein MA. Racial differences in infant mortality attributable to birth defects in the United States, 1989-2002. Birth Defects Res A Clin Mol Teratol. 2006 Oct;76(10):706-13. doi: 10.1002/bdra.20308.
PMID: 17022030
citation: Yang Q, Khoury MJ, Mannino D. Trends and patterns of mortality associated with birth defects and genetic diseases in the United States, 1979-1992: an analysis of multiple-cause mortality data. Genet Epidemiol. 1997;14(5):493-505. doi: 10.1002/(SICI)1098-2272(1997)14:53.0.CO;2-2.
PMID: 9358267
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citation: Parr GV, Blackstone EH, Kirklin JW. Cardiac performance and mortality early after intracardiac surgery in infants and young children. Circulation. 1975 May;51(5):867-74. doi: 10.1161/01.cir.51.5.867.
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citation: Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castaneda AR, Newburger JW, Wessel DL. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation. 1995 Oct 15;92(8):2226-35. doi: 10.1161/01.cir.92.8.2226.
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citation: Wan S, LeClerc JL, Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest. 1997 Sep;112(3):676-92. doi: 10.1378/chest.112.3.676.
PMID: 9315800
citation: Ando M, Park IS, Wada N, Takahashi Y. Steroid supplementation: a legitimate pharmacotherapy after neonatal open heart surgery. Ann Thorac Surg. 2005 Nov;80(5):1672-8; discusison 1678. doi: 10.1016/j.athoracsur.2005.04.035.
PMID: 16242437
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PMID: 10881828
citation: Checchia PA, Backer CL, Bronicki RA, Baden HP, Crawford SE, Green TP, Mavroudis C. Dexamethasone reduces postoperative troponin levels in children undergoing cardiopulmonary bypass. Crit Care Med. 2003 Jun;31(6):1742-5. doi: 10.1097/01.CCM.0000063443.32874.60.
PMID: 12794414
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PMID: 21600592
citation: Graham EM, Atz AM, McHugh KE, Butts RJ, Baker NL, Stroud RE, Reeves ST, Bradley SM, McGowan FX Jr, Spinale FG. Preoperative steroid treatment does not improve markers of inflammation after cardiac surgery in neonates: results from a randomized trial. J Thorac Cardiovasc Surg. 2014 Mar;147(3):902-8. doi: 10.1016/j.jtcvs.2013.06.010. Epub 2013 Jul 16.
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PMID: 16340373
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Kevin Hill
investigator title: Associate Professor of Pediatrics
mesh term: Heart Diseases
mesh term: Heart Defects, Congenital
mesh term: Inflammation
mesh term: Methylprednisolone
mesh term: Methylprednisolone Acetate
mesh term: Methylprednisolone Hemisuccinate
mesh term: Prednisolone
mesh term: Prednisolone acetate
mesh term: Prednisolone hemisuccinate
mesh term: Prednisolone phosphate
sharing ipd: Yes
ipd description: The investigators will disseminate findings through publications, national presentations, participation in the CTSA Consortium, the CTSA website and via the existing infrastructure of the Society of Thoracic Surgeons Congenital Heart Surgery Database. Data collection supported by CTSA funds will follow the principles outlined in the Final NIH Statement on Sharing Research Data. Participating institutions will honor the principle that data sharing is critical for expeditious translation of research findings to the improvement of human health. The investigators abide strictly by the provisions of the Health Insurance Portability and Accountability Act (HIPAA). The investigators will continue to use traditional venues for data sharing, such as publications in leading scientific journals and deposit all applicable NIH-funded research results to PubMed Central in compliance with the NIH's Public Access Policy.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 