xml: <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/NCT05981079</url>
    </required_header>
    <id_info>
      <org_study_id>SDU-2023-NeoPIP-002</org_study_id>
      <nct_id>NCT05981079</nct_id>
    </id_info>
    <brief_title>Model-based Dose Versus Empirical Dose of Piperacillin/Tazobactam in Preterm Neonates With Late-onset Sepsis.</brief_title>
    <acronym>PIP/TAZO</acronym>
    <official_title>Model-based Dose Versus Empirical Dose of Piperacillin/Tazobactam in the Treatment of Late-onset Sepsis in Preterm Neonates: a Multicentre, Randomised, Open-label, Non-inferiority Study.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shandong University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Shandong Provincial Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Qianfoshan Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Jinan Maternity and Child Care Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Yantai Yuhuangding Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Hebei Petro China Center Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Shengli Oilfield Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Liaocheng People's Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Jining Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>W.F. Maternal and Child Health Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Taian City Central Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Shandong University</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 study aims to compare the clinical outcomes, safety and PD target attainment of the&#xD;
        model-based dose and empirical dose of piperacillin/tazobactam in the treatment of LOS in&#xD;
        premature neonates, so as to optimize the piperacillin/tazobactam dose regimen.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 31, 2023</start_date>
    <completion_date type="Anticipated">May 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <phase>Phase 4</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>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Successful outcome</measure>
      <time_frame>At the follow-up visit (10 ± 1 days after the end of actual piperacillin/tazobactam therapy )</time_frame>
      <description>Successful outcome is defined as:&#xD;
  Participant is alive.&#xD;
  No need for replacing the antibiotic or adding new antibiotics.&#xD;
  At the end of actual piperacillin/tazobactam therapy, ①there is a significant improvement in the participant's overall clinical status, ②there is microbiological resolution or presumed eradication of bacteria and ③no new piperacillin/tazobactam-susceptible pathogens potentially associated with sepsis have been identified.&#xD;
  Participant does not have a clinically or microbiologically significant relapse or new infection within 10 days after the end of actual piperacillin/tazobactam therapy.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Length of NICU stay</measure>
      <time_frame>From the date of randomization until date of discharge, assessed up to 2 months</time_frame>
      <description>Duration of hospital admission (days)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>All cause in-hospital mortality</measure>
      <time_frame>From the date of randomization until date of discharge, assessed up to 2 months</time_frame>
      <description>Death before discharge from NICU</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of patients switching to or adding another antibiotics.</measure>
      <time_frame>Through study completion, an average of 20 days.</time_frame>
      <description>Proportion of patients switching to or adding another antibiotics by any reason.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Relapsed or new infection rate</measure>
      <time_frame>At the follow-up visit (10 ± 1 days after the end of actual piperacillin/tazobactam therapy )</time_frame>
      <description>Proportion of patients with clinically or microbiologically significant relapsed or new infection.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PD target attainment</measure>
      <time_frame>Through study completion, an average of 20 days.</time_frame>
      <description>70%fT&gt;MIC</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse events</measure>
      <time_frame>Through study completion, an average of 20 days.</time_frame>
      <description>Drug-related adverse events and serious adverse events</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">332</enrollment>
    <condition>Late-Onset Neonatal Sepsis</condition>
    <arm_group>
      <arm_group_label>Model-based dosing regimen</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: Piperacillin Sodium and Tazobactam Sodium for Injection. Dosing regimen: GA&lt;28 weeks: 30 mg/kg, Q8H; 28 weeks ≤GA&lt;34 weeks: 50 mg/kg，Q8H.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Empirical dosing regimen</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Drug: Piperacillin Sodium and Tazobactam Sodium for Injection. Dosing regimen: 90 mg/kg，Q8H.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Piperacillin/tazobactam</intervention_name>
      <description>Piperacillin Sodium and Tazobactam Sodium for Injection</description>
      <arm_group_label>Empirical dosing regimen</arm_group_label>
      <arm_group_label>Model-based dosing regimen</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Preterm neonates: gestational age &lt;34 weeks;&#xD;
  &#xD;
            -  Postnatal age &gt; 72h;&#xD;
  &#xD;
            -  Postmenstrual age &lt;36 weeks;&#xD;
  &#xD;
            -  Newly diagnosed as late-onset sepsis;&#xD;
  &#xD;
            -  Parental written consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patient with bacterial meningitis, osteomyelitis, septic arthritis or necrotizing&#xD;
               enterocolitis requiring surgery.&#xD;
  &#xD;
            -  High suspicion of/confirmed fungal infection.&#xD;
  &#xD;
            -  Severe congenital malformations and/or severe organ failure.&#xD;
  &#xD;
            -  Administration of any systemic antibiotic regimen 24 h before screening.&#xD;
  &#xD;
            -  Administration of other systemic trial drug therapy.&#xD;
  &#xD;
            -  Other factors that the researcher considers unsuitable for inclusion.&#xD;
  &#xD;
            -  Post-randomization Exclusion: ①Patients with a positive baseline blood culture and the&#xD;
               pathogen resistant to PIP/TAZO. ②Patients with bacterial meningitis, fungal infection,&#xD;
               osteomyelitis, septic arthritis or necrotizing enterocolitis requiring surgery after&#xD;
               randomization.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>72 Hours</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Wei Zhao, Ph.D</last_name>
      <role>Principal Investigator</role>
      <affiliation>Shandong University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Wei Zhao, Ph.D</last_name>
      <phone>+8653188383308</phone>
      <email>zhao4wei2@hotmail.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Shengli Oilfield Hospital</name>
        <address>
          <city>Dongying</city>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Zhihua Liu</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Jinan Maternity and Child Care Hospital</name>
        <address>
          <city>Jinan</city>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Wenwen Zhang</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Qianfoshan Hospital</name>
        <address>
          <city>Jinan</city>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Dejuan Yang</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Shandong Provincial Hospital</name>
        <address>
          <city>Jinan</city>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Yonghui Yu</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Jining Medical University</name>
        <address>
          <city>Jining</city>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Ru Yang</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hebei Petro China Center Hospital</name>
        <address>
          <city>Langfang</city>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Huan Li</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Liaocheng People's Hospital</name>
        <address>
          <city>Liaocheng</city>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Lili Zhao</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Taian City Central Hospital</name>
        <address>
          <city>Tai'an</city>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Guo Yao</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>W.F. Maternal and Child Health Hospital</name>
        <address>
          <city>Weifang</city>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Ying Zhou</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Yantai Yuhuangding Hospital</name>
        <address>
          <city>Yantai</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Shanshan Hou</last_name>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 14, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>July 31, 2023</last_update_submitted>
    <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Shandong University</investigator_affiliation>
      <investigator_full_name>Wei Zhao</investigator_full_name>
      <investigator_title>Head of department of clinical pharmacy and pharmacology</investigator_title>
    </responsible_party>
    <keyword>late-onset sepsis</keyword>
    <keyword>piperacillin/tazobactam</keyword>
    <keyword>model-based dose</keyword>
    <keyword>empirical dose</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Sepsis</mesh_term>
      <mesh_term>Toxemia</mesh_term>
      <mesh_term>Neonatal Sepsis</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tazobactam</mesh_term>
      <mesh_term>Piperacillin</mesh_term>
      <mesh_term>Piperacillin, Tazobactam Drug Combination</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05981079
  org study id: SDU-2023-NeoPIP-002
  nct id: NCT05981079
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  This study aims to compare the clinical outcomes, safety and PD target attainment of the
        model-based dose and empirical dose of piperacillin/tazobactam in the treatment of LOS in
        premature neonates, so as to optimize the piperacillin/tazobactam dose regimen.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Successful outcome
  time frame: At the follow-up visit (10 ± 1 days after the end of actual piperacillin/tazobactam therapy )
  description: Successful outcome is defined as:
  Participant is alive.
  No need for replacing the antibiotic or adding new antibiotics.
  At the end of actual piperacillin/tazobactam therapy, ①there is a significant improvement in the participant's overall clinical status, ②there is microbiological resolution or presumed eradication of bacteria and ③no new piperacillin/tazobactam-susceptible pathogens potentially associated with sepsis have been identified.
  Participant does not have a clinically or microbiologically significant relapse or new infection within 10 days after the end of actual piperacillin/tazobactam therapy.
  measure: Length of NICU stay
  time frame: From the date of randomization until date of discharge, assessed up to 2 months
  description: Duration of hospital admission (days)
  measure: All cause in-hospital mortality
  time frame: From the date of randomization until date of discharge, assessed up to 2 months
  description: Death before discharge from NICU
  measure: Proportion of patients switching to or adding another antibiotics.
  time frame: Through study completion, an average of 20 days.
  description: Proportion of patients switching to or adding another antibiotics by any reason.
  measure: Relapsed or new infection rate
  time frame: At the follow-up visit (10 ± 1 days after the end of actual piperacillin/tazobactam therapy )
  description: Proportion of patients with clinically or microbiologically significant relapsed or new infection.
  measure: PD target attainment
  time frame: Through study completion, an average of 20 days.
  description: 70%fT>MIC
  measure: Adverse events
  time frame: Through study completion, an average of 20 days.
  description: Drug-related adverse events and serious adverse events
  arm group label: Model-based dosing regimen
  arm group type: Experimental
  description: Drug: Piperacillin Sodium and Tazobactam Sodium for Injection. Dosing regimen: GA<28 weeks: 30 mg/kg, Q8H; 28 weeks ≤GA<34 weeks: 50 mg/kg，Q8H.
  arm group label: Empirical dosing regimen
  arm group type: Active Comparator
  description: Drug: Piperacillin Sodium and Tazobactam Sodium for Injection. Dosing regimen: 90 mg/kg，Q8H.
  intervention type: Drug
  intervention name: Piperacillin/tazobactam
  description: Piperacillin Sodium and Tazobactam Sodium for Injection
  arm group label: Empirical dosing regimen
  arm group label: Model-based dosing regimen
  criteria: 
  gender: All
  minimum age: 72 Hours
  maximum age: N/A
  healthy volunteers: No
  last name: Wei Zhao, Ph.D
  role: Principal Investigator
  affiliation: Shandong University
  last name: Wei Zhao, Ph.D
  phone: +8653188383308
  email: zhao4wei2@hotmail.com
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Shandong University
  investigator full name: Wei Zhao
  investigator title: Head of department of clinical pharmacy and pharmacology
  mesh term: Sepsis
  mesh term: Toxemia
  mesh term: Neonatal Sepsis
  mesh term: Tazobactam
  mesh term: Piperacillin
  mesh term: Piperacillin, Tazobactam Drug Combination