<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/NCT04469413</url>
  </required_header>
  <id_info>
    <org_study_id>113/2019</org_study_id>
    <nct_id>NCT04469413</nct_id>
  </id_info>
  <brief_title>Comparison of Infusion Paracetamol Protocols in PDA</brief_title>
  <official_title>Comparison of The Effect of Continuous and Standard Intermittent Boluses Paracetamol Infusion on Patent Ductus Arteriosus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ankara University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ankara University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study was to evaluate the effect of paracetamol on patent ductus arteriosus&#xD;
      (PDA) closure and clinical outcomes in preterm infants when used as standard intermittent&#xD;
      bolus and continuous intravenous (IV) infusion. Preterm neonates with birth weight (BW) ≤1500&#xD;
      g and gestational age (GA) ≤32 weeks were included in this study. During the study period, IV&#xD;
      paracetamol therapy was given to all infants with hemodynamically significant patent ductus&#xD;
      arteriosus (hsPDA). The patients were divided into the standard IV intermittent bolus&#xD;
      infusion group and the continuous IV infusion group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Demographic and clinical features Perinatal variables were recorded for all infants,&#xD;
      including GA, BW, sex, APGAR scores (at 1 and 5 minutes), prenatal steroids, pre- and&#xD;
      post-treatment alanine aminotransferase (ALT)/aspartate aminotransferase (AST), second and&#xD;
      third courses of paracetamol, PDA ligation, clinical variables including respiratory distress&#xD;
      syndrome (RDS), IVH (grade ≥3), NEC (grade≥2), moderate or severe BPD, ROP requiring laser&#xD;
      therapy, early-onset neonatal sepsis (EOS), late-onset sepsis (LOS), duration of non-invasive&#xD;
      ventilation (NIV), mechanical ventilation (MV) and oxygen (O2) supplementation, day of full&#xD;
      enteral feeding achievement, length of hospital stay, and mortality.&#xD;
&#xD;
      Sepsis with onset at ≤72 hours was defined as EOS and at &gt;72 hours as LOS in infants&#xD;
      hospitalized in the NICU. RDS was defined as the need for surfactant administration [5]. IVH&#xD;
      was diagnosed by cranial ultrasound in the first 7 days of life (intraparenchymal hemorrhage&#xD;
      + IVH, large IVH). NEC diagnosis and staging were implemented by using Bell's criteria.&#xD;
      Neonates that received positive pressure or ≥30% oxygen without pressure after a&#xD;
      postmenstrual age of 36 weeks were diagnosed as having moderate or severe BPD [8]. ROP&#xD;
      screening was done by ophthalmologists according to the International Classification of&#xD;
      Retinopathy of Prematurity Revisited [9].&#xD;
&#xD;
      Hemodynamically Significant Patent Ductus Arteriosus All neonates underwent Doppler&#xD;
      echocardiography (ECHO) at postnatal 72 hours. Diagnosis of hsPDA was based on clinical and&#xD;
      ECHO features [10]. ECHO evaluation was repeated at regular intervals. IV paracetamol was&#xD;
      used as primary rescue therapy for hsDPA. If hsPDA persisted despite 3 courses of paracetamol&#xD;
      therapy, surgical ligation was performed. The non-hsPDA group comprised non-hsPDA preterm&#xD;
      infants selected using the same exclusion criteria. Infants with non-hsPDA were excluded from&#xD;
      the study.&#xD;
&#xD;
      Continuous and Standard Intermittent Bolus Infusion of Paracetamol IV paracetamol therapy was&#xD;
      delivered as primary rescue pharmacological treatment to all neonates who had hsPDA during&#xD;
      the study period. Standard IV intermittent bolus paracetamol therapy was administered in the&#xD;
      form of 15 mg/kg doses as 1-hour infusions every 6 hours for 5 days, while continuous IV&#xD;
      paracetamol infusion therapy was administered as a 60 mg/kg/day dose continuously for 5 days&#xD;
      (Parol, Atabay Ilac Kimya San., Istanbul, Turkey). ALT and AST levels were analyzed before&#xD;
      and after treatment . Infants received standard IV intermittent bolus paracetamol between&#xD;
      January 1 and April 31, 2018, and continuous IV infusion paracetamol between May 1 - August&#xD;
      31, 2018 for hsPDA medical treatment. Therefore, eligible infants were divided into two&#xD;
      groups as the standard IV intermittent bolus infusion group and the continuous IV infusion&#xD;
      group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Actual">January 6, 2020</completion_date>
  <primary_completion_date type="Actual">August 1, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Patent Ductus Arteriosus</measure>
    <time_frame>6 months</time_frame>
    <description>PDA-related morbidities, multiple paracetamol courses, and PDA ligation</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">138</enrollment>
  <condition>Patent Ductus Arteriosus in Preterm Infants</condition>
  <arm_group>
    <arm_group_label>standard IV intermittent bolus infusion group</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>continuousIV intermittent bolus infusion group</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paracetamol Infusion</intervention_name>
    <description>Continuous and Standard Intermittent Boluses Paracetamol Infusion</description>
    <arm_group_label>continuousIV intermittent bolus infusion group</arm_group_label>
    <arm_group_label>standard IV intermittent bolus infusion group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Preterm preterms with birth weight (BW) ≤1500 g and gestational age (GA) ≤32 weeks will be&#xD;
        included in the study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        birth weight (BW) ≤1500 g and gestational age (GA) ≤32 weeks at birth&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        birth weight (BW) &gt;1500 g and gestational age (GA) &gt;32 weeks at birth&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>1 Month</maximum_age>
  </eligibility>
  <location>
    <facility>
      <name>Ufuk Cakir</name>
      <address>
        <city>Ankara</city>
        <zip>06130</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>July 9, 2020</last_update_submitted>
  <last_update_submitted_qc>July 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ankara University</investigator_affiliation>
    <investigator_full_name>Ufuk Cakir</investigator_full_name>
    <investigator_title>Ankara University</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ductus Arteriosus, Patent</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</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/NCT04469413
org study id: 113/2019
nct id: NCT04469413
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this study was to evaluate the effect of paracetamol on patent ductus arteriosus
      (PDA) closure and clinical outcomes in preterm infants when used as standard intermittent
      bolus and continuous intravenous (IV) infusion. Preterm neonates with birth weight (BW) ≤1500
      g and gestational age (GA) ≤32 weeks were included in this study. During the study period, IV
      paracetamol therapy was given to all infants with hemodynamically significant patent ductus
      arteriosus (hsPDA). The patients were divided into the standard IV intermittent bolus
      infusion group and the continuous IV infusion group.
Demographic and clinical features Perinatal variables were recorded for all infants,
      including GA, BW, sex, APGAR scores (at 1 and 5 minutes), prenatal steroids, pre- and
      post-treatment alanine aminotransferase (ALT)/aspartate aminotransferase (AST), second and
      third courses of paracetamol, PDA ligation, clinical variables including respiratory distress
      syndrome (RDS), IVH (grade ≥3), NEC (grade≥2), moderate or severe BPD, ROP requiring laser
      therapy, early-onset neonatal sepsis (EOS), late-onset sepsis (LOS), duration of non-invasive
      ventilation (NIV), mechanical ventilation (MV) and oxygen (O2) supplementation, day of full
      enteral feeding achievement, length of hospital stay, and mortality.

      Sepsis with onset at ≤72 hours was defined as EOS and at >72 hours as LOS in infants
      hospitalized in the NICU. RDS was defined as the need for surfactant administration [5]. IVH
      was diagnosed by cranial ultrasound in the first 7 days of life (intraparenchymal hemorrhage
      + IVH, large IVH). NEC diagnosis and staging were implemented by using Bell's criteria.
      Neonates that received positive pressure or ≥30% oxygen without pressure after a
      postmenstrual age of 36 weeks were diagnosed as having moderate or severe BPD [8]. ROP
      screening was done by ophthalmologists according to the International Classification of
      Retinopathy of Prematurity Revisited [9].

      Hemodynamically Significant Patent Ductus Arteriosus All neonates underwent Doppler
      echocardiography (ECHO) at postnatal 72 hours. Diagnosis of hsPDA was based on clinical and
      ECHO features [10]. ECHO evaluation was repeated at regular intervals. IV paracetamol was
      used as primary rescue therapy for hsDPA. If hsPDA persisted despite 3 courses of paracetamol
      therapy, surgical ligation was performed. The non-hsPDA group comprised non-hsPDA preterm
      infants selected using the same exclusion criteria. Infants with non-hsPDA were excluded from
      the study.

      Continuous and Standard Intermittent Bolus Infusion of Paracetamol IV paracetamol therapy was
      delivered as primary rescue pharmacological treatment to all neonates who had hsPDA during
      the study period. Standard IV intermittent bolus paracetamol therapy was administered in the
      form of 15 mg/kg doses as 1-hour infusions every 6 hours for 5 days, while continuous IV
      paracetamol infusion therapy was administered as a 60 mg/kg/day dose continuously for 5 days
      (Parol, Atabay Ilac Kimya San., Istanbul, Turkey). ALT and AST levels were analyzed before
      and after treatment . Infants received standard IV intermittent bolus paracetamol between
      January 1 and April 31, 2018, and continuous IV infusion paracetamol between May 1 - August
      31, 2018 for hsPDA medical treatment. Therefore, eligible infants were divided into two
      groups as the standard IV intermittent bolus infusion group and the continuous IV infusion
      group.
observational model: Cohort
time perspective: Retrospective
measure: Patent Ductus Arteriosus
time frame: 6 months
description: PDA-related morbidities, multiple paracetamol courses, and PDA ligation
arm group label: standard IV intermittent bolus infusion group
arm group label: continuousIV intermittent bolus infusion group
intervention type: Drug
intervention name: Paracetamol Infusion
description: Continuous and Standard Intermittent Boluses Paracetamol Infusion
arm group label: continuousIV intermittent bolus infusion group
arm group label: standard IV intermittent bolus infusion group
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 1 Month
facility: 
country: Turkey
responsible party type: Principal Investigator
investigator affiliation: Ankara University
investigator full name: Ufuk Cakir
investigator title: Ankara University
mesh term: Ductus Arteriosus, Patent
mesh term: Acetaminophen
sharing ipd: Undecided