<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/NCT03823781</url>
  </required_header>
  <id_info>
    <org_study_id>SCMCIRB-K2018105</org_study_id>
    <nct_id>NCT03823781</nct_id>
  </id_info>
  <brief_title>Prophylactic Use of Milrinone After Congenital Heart Surgery in Infants</brief_title>
  <official_title>Prophylactic Milrinone Infusion for the Prevention Low Cardiac Output Syndrome After Corrective Surgery for Congenital Heart Disease in Infants: A Randomized, Multi-center, Double-blinded, Placebo-controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Children's Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Children's Medical Center</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized, multi-center, double-blinded, placebo-controlled study is designed to&#xD;
      evaluate the efficacy and safety of milrinone compared with placebo in participants after&#xD;
      corrective surgery for congenital heart disease. Participants will be randomized in a 1:1&#xD;
      ratio within 90 minutes after arriving in the intensive care unit (ICU), to receive either&#xD;
      intravenous milrinone or placebo for 36 hours. Participants will be stratified according&#xD;
      Vasoactive Inotrope Score after arriving in the ICU.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">February 2019</start_date>
  <completion_date type="Anticipated">July 2021</completion_date>
  <primary_completion_date type="Anticipated">January 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants died within 30 days postoperatively</measure>
    <time_frame>up to 30 days postoperatively</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants developed low cardiac output syndrome within the first 36 hours after initiation of study drug</measure>
    <time_frame>36 hours after initiation of study drug</time_frame>
    <description>Low cardiac output syndrome was defined as the following: clinical signs or symptoms (eg, tachycardia, oliguria, poor perfusion, or cardiac arrest) with or without a widened arterial-mixed venous oxygen saturation difference or metabolic acidosis; mechanical support of the circulation (eg, extracorporeal life support, ventricular assist device), a cardiac index determined by Pulse indicator continuous cardiac output (PiCCO) of &lt;2.2 L/min/m2</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants developed low cardiac output syndrome in the interval between 36 hours after initiation of study drug and the final Follow up. Cardiac index will be determined by Doppler echocardiography</measure>
    <time_frame>up to 30 days postoperatively</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Vasoactive Inotrope Score.</measure>
    <time_frame>36 hours after initiation of study drug</time_frame>
    <description>Vasoactive Inotrope Score=100*Epinephrine dose (ug/kg/min)+100*Norepinephrine dose (ug/kg/min)+10*Dopamine dose (ug/kg/min)+10*Dobutamine dose (ug/kg/min) +10,000*Vasopressin dose (units/kg/min) +10*Milrinone dose (ug/kg/min)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of intensive care stay.</measure>
    <time_frame>up to 30 days postoperatively or until ICU discharge.</time_frame>
    <description>Length of intensive care stay will be calculated from date of ICU admission to date of ICU discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay.</measure>
    <time_frame>up to 30 days postoperatively or until hospital discharge</time_frame>
    <description>Length of hospital stay will be calculated from date of hospital admission to date of hospital discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of mechanical ventilation.</measure>
    <time_frame>up to 30 days postoperatively or until extubation</time_frame>
    <description>Duration of mechanical ventilation will be calculated from date and time of ICU admission to date and time of extubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with improvement of ventriculoarterial coupling</measure>
    <time_frame>36 hours after initiation of study drug</time_frame>
    <description>ventriculoarterial coupling improvement will be assessed by means of ventriculoarterial coupling values shift closer to 1. ventriculoarterial coupling will be obtained as : (1-EF)/EF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants requiring mechanical circulatory support.</measure>
    <time_frame>up to 30 days postoperatively</time_frame>
    <description>eg. Extra-Corporeal Membrane Oxygenation, ventricular assist device</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with a decrease in regional tissue oxygenation at least 20% from baseline.</measure>
    <time_frame>36 hours after initiation of study drug</time_frame>
    <description>Cerebral and abdominal regional tissue oxygenation will be monitored</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events</measure>
    <time_frame>36 hours after initiation of study drug</time_frame>
    <description>Treatment-related adverse events will be evaluated by sponsor's drug safety surveillance reviewer</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">520</enrollment>
  <condition>Low Cardiac Output Syndrome</condition>
  <condition>Cardiac Surgical Procedures</condition>
  <condition>Infant</condition>
  <arm_group>
    <arm_group_label>milrinone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>milrinone milrinone will be administered intravenously at a rate of 0.75ug/kg/min for 35 hours, and baseline catecholamines will be administered at the discretion of the physician.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>normal saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo placebo (normal saline) will be administered intravenously for 35 hours, and baseline catecholamines will be administered at the discretion of the physician.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Milrinone</intervention_name>
    <description>The study intervention is an intravenous infusion of milrinone or placebo.</description>
    <arm_group_label>milrinone</arm_group_label>
    <other_name>Milrinone Lactate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal saline</intervention_name>
    <description>The study intervention is an intravenous infusion of milrinone or placebo.</description>
    <arm_group_label>normal saline</arm_group_label>
    <other_name>Normal Saline 0.9% Infusion Solution Bag</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age younger than 12 months&#xD;
&#xD;
          -  Without pre-operative low cardiac output syndrome&#xD;
&#xD;
          -  Bi-ventricular repair of congenital heart disease involving cardiopulmonary bypass&#xD;
&#xD;
          -  Informed consent obtained from each participant's parent or guardian&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A body weight &lt;2 kg&#xD;
&#xD;
          -  Prematurity (birth &lt;36 weeks postconceptual age)&#xD;
&#xD;
          -  Renal dysfunction ( Creatinine&gt;1.5mg/dL 48 hours before surgery)&#xD;
&#xD;
          -  Low cardiac output syndrome or hypotension on arrival to ICU from OR&#xD;
&#xD;
          -  Cardiopulmonary resuscitation before surgery&#xD;
&#xD;
          -  Platelet count&lt;80,000/mm3 before surgery&#xD;
&#xD;
          -  Left ventricular outflow tract obstruction before surgery&#xD;
&#xD;
          -  Ventricular arrhythmia before surgery&#xD;
&#xD;
          -  Without femoral artery catheter before arriving in the ICU&#xD;
&#xD;
          -  Consent was withdrawn by participants' parent or guardian.&#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>Huiwen Chen, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Department of clinical research, Shanghai children's medical center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jihong Huang, MD, PhD</last_name>
    <phone>+8618930830766</phone>
    <email>huangjihong@scmc.com.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zhuoming Xu, MD, PhD</last_name>
    <phone>+8618930830783</phone>
    <email>xuzhuoming@scmc.com.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Shanghai Shanghai Children's Medical Center</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200127</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jihong Huang, MD, PhD</last_name>
      <phone>+8618930830766</phone>
      <email>huangjihong@scmc.com.cn</email>
    </contact>
    <contact_backup>
      <last_name>Chunxiang Li, MD</last_name>
      <phone>+8618916611383</phone>
      <email>lichunxiang@scmc.com.cn</email>
    </contact_backup>
    <investigator>
      <last_name>Huiwen Chen, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 29, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>January 29, 2019</last_update_submitted>
  <last_update_submitted_qc>January 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiac Output, Low</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Milrinone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03823781
org study id: SCMCIRB-K2018105
nct id: NCT03823781
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This randomized, multi-center, double-blinded, placebo-controlled study is designed to
      evaluate the efficacy and safety of milrinone compared with placebo in participants after
      corrective surgery for congenital heart disease. Participants will be randomized in a 1:1
      ratio within 90 minutes after arriving in the intensive care unit (ICU), to receive either
      intravenous milrinone or placebo for 36 hours. Participants will be stratified according
      Vasoactive Inotrope Score after arriving in the ICU.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of participants died within 30 days postoperatively
time frame: up to 30 days postoperatively
measure: Number of participants developed low cardiac output syndrome within the first 36 hours after initiation of study drug
time frame: 36 hours after initiation of study drug
description: Low cardiac output syndrome was defined as the following: clinical signs or symptoms (eg, tachycardia, oliguria, poor perfusion, or cardiac arrest) with or without a widened arterial-mixed venous oxygen saturation difference or metabolic acidosis; mechanical support of the circulation (eg, extracorporeal life support, ventricular assist device), a cardiac index determined by Pulse indicator continuous cardiac output (PiCCO) of <2.2 L/min/m2
measure: Number of participants developed low cardiac output syndrome in the interval between 36 hours after initiation of study drug and the final Follow up. Cardiac index will be determined by Doppler echocardiography
time frame: up to 30 days postoperatively
measure: Change in Vasoactive Inotrope Score.
time frame: 36 hours after initiation of study drug
description: Vasoactive Inotrope Score=100*Epinephrine dose (ug/kg/min)+100*Norepinephrine dose (ug/kg/min)+10*Dopamine dose (ug/kg/min)+10*Dobutamine dose (ug/kg/min) +10,000*Vasopressin dose (units/kg/min) +10*Milrinone dose (ug/kg/min)
measure: Length of intensive care stay.
time frame: up to 30 days postoperatively or until ICU discharge.
description: Length of intensive care stay will be calculated from date of ICU admission to date of ICU discharge
measure: Length of hospital stay.
time frame: up to 30 days postoperatively or until hospital discharge
description: Length of hospital stay will be calculated from date of hospital admission to date of hospital discharge
measure: Duration of mechanical ventilation.
time frame: up to 30 days postoperatively or until extubation
description: Duration of mechanical ventilation will be calculated from date and time of ICU admission to date and time of extubation
measure: Number of participants with improvement of ventriculoarterial coupling
time frame: 36 hours after initiation of study drug
description: ventriculoarterial coupling improvement will be assessed by means of ventriculoarterial coupling values shift closer to 1. ventriculoarterial coupling will be obtained as : (1-EF)/EF
measure: Number of participants requiring mechanical circulatory support.
time frame: up to 30 days postoperatively
description: eg. Extra-Corporeal Membrane Oxygenation, ventricular assist device
measure: Number of participants with a decrease in regional tissue oxygenation at least 20% from baseline.
time frame: 36 hours after initiation of study drug
description: Cerebral and abdominal regional tissue oxygenation will be monitored
measure: Number of participants with treatment-related adverse events
time frame: 36 hours after initiation of study drug
description: Treatment-related adverse events will be evaluated by sponsor's drug safety surveillance reviewer
arm group label: milrinone
arm group type: Experimental
description: milrinone milrinone will be administered intravenously at a rate of 0.75ug/kg/min for 35 hours, and baseline catecholamines will be administered at the discretion of the physician.
arm group label: normal saline
arm group type: Placebo Comparator
description: placebo placebo (normal saline) will be administered intravenously for 35 hours, and baseline catecholamines will be administered at the discretion of the physician.
intervention type: Drug
intervention name: Milrinone
description: The study intervention is an intravenous infusion of milrinone or placebo.
arm group label: milrinone
other name: Milrinone Lactate
intervention type: Drug
intervention name: Normal saline
description: The study intervention is an intravenous infusion of milrinone or placebo.
arm group label: normal saline
other name: Normal Saline 0.9% Infusion Solution Bag
criteria: 
gender: All
minimum age: N/A
maximum age: 12 Months
healthy volunteers: No
last name: Huiwen Chen, MD, PhD
role: Study Director
affiliation: Department of clinical research, Shanghai children's medical center
last name: Jihong Huang, MD, PhD
phone: +8618930830766
email: huangjihong@scmc.com.cn
last name: Zhuoming Xu, MD, PhD
phone: +8618930830783
email: xuzhuoming@scmc.com.cn
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Cardiac Output, Low
mesh term: Syndrome
mesh term: Milrinone
sharing ipd: Undecided