Model-based Dose Versus Empirical Dose of Piperacillin/Tazobactam in Preterm Neonates With Late-onset Sepsis. (PIP/TAZO)

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Late-Onset Neonatal Sepsis
• Intervention / Treatment: Drug: Piperacillin/tazobactam

• Study Type: Interventional
• Enrollment (Estimated): 332
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Wei Zhao, Ph.D; Phone Number: +8653188383308; Email: zhao4wei2@hotmail.com

Study Locations

• China
  • Dongying, China
    • Not yet recruiting
    • Shengli Oilfield Hospital
    • Contact: Zhihua Liu
  • Jinan, China
    • Not yet recruiting
    • Shandong Provincial Hospital
    • Contact: Yonghui Yu
  • Jinan, China
    • Not yet recruiting
    • Jinan Maternity and Child Care Hospital
    • Contact: Wenwen Zhang
  • Jinan, China
    • Not yet recruiting
    • Qianfoshan Hospital
    • Contact: Dejuan Yang
  • Jining, China
    • Not yet recruiting
    • Jining Medical University
    • Contact: Ru Yang
  • Langfang, China
    • Not yet recruiting
    • Hebei Petro China Center Hospital
    • Contact: Huan Li
  • Liaocheng, China
    • Not yet recruiting
    • Liaocheng People's Hospital
    • Contact: Lili Zhao
  • Tai'an, China
    • Not yet recruiting
    • Taian City Central Hospital
    • Contact: Guo Yao
  • Weifang, China
    • Not yet recruiting
    • W.F. Maternal and Child Health Hospital
    • Contact: Ying Zhou
  • Yantai, China
    • Recruiting
    • Yantai Yuhuangding Hospital
    • Contact: Shanshan Hou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Preterm neonates: gestational age <34 weeks;
• Postnatal age > 72h;
• Postmenstrual age <36 weeks;
• Newly diagnosed as late-onset sepsis;
• Parental written consent.

Exclusion Criteria:

• Patient with bacterial meningitis, osteomyelitis, septic arthritis or necrotizing enterocolitis requiring surgery.
• High suspicion of/confirmed fungal infection.
• Severe congenital malformations and/or severe organ failure.
• Administration of any systemic antibiotic regimen 24 h before screening.
• Administration of other systemic trial drug therapy.
• Other factors that the researcher considers unsuitable for inclusion.
• Post-randomization Exclusion: ①Patients with a positive baseline blood culture and the pathogen resistant to PIP/TAZO. ②Patients with bacterial meningitis, fungal infection, osteomyelitis, septic arthritis or necrotizing enterocolitis requiring surgery after randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Model-based dosing regimen; 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.	Drug: Piperacillin/tazobactam; Piperacillin Sodium and Tazobactam Sodium for Injection
Active Comparator: Empirical dosing regimen; Drug: Piperacillin Sodium and Tazobactam Sodium for Injection. Dosing regimen: 90 mg/kg，Q8H.	Drug: Piperacillin/tazobactam; Piperacillin Sodium and Tazobactam Sodium for Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful outcome	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.	At the follow-up visit (10 ± 1 days after the end of actual piperacillin/tazobactam therapy )

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of NICU stay	Duration of hospital admission (days)	From the date of randomization until date of discharge, assessed up to 2 months
All cause in-hospital mortality	Death before discharge from NICU	From the date of randomization until date of discharge, assessed up to 2 months
Proportion of patients switching to or adding another antibiotics.	Proportion of patients switching to or adding another antibiotics by any reason.	Through study completion, an average of 20 days.
Relapsed or new infection rate	Proportion of patients with clinically or microbiologically significant relapsed or new infection.	At the follow-up visit (10 ± 1 days after the end of actual piperacillin/tazobactam therapy )
PD target attainment	70%fT>MIC	Through study completion, an average of 20 days.
Adverse events	Drug-related adverse events and serious adverse events	Through study completion, an average of 20 days.

Collaborators and Investigators

• Sponsor: Shandong University
• Collaborators: Shandong Provincial Hospital; Qianfoshan Hospital; Jining Medical University; Yantai Yuhuangding Hospital; Liaocheng People's Hospital; Taian City Central Hospital; Shengli Oilfield Hospital; Jinan Maternity and Child Care Hospital; Hebei Petro China Center Hospital; W.F. Maternal and Child Health Hospital
• Investigators: Principal Investigator: Wei Zhao, Ph.D, Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: July 14, 2023
• First Submitted That Met QC Criteria: July 31, 2023
• First Posted (Actual): August 8, 2023

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: piperacillin/tazobactam; late-onset sepsis; model-based dose; empirical dose
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Sepsis; Toxemia; Neonatal Sepsis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination
• Other Study ID Numbers: SDU-2023-NeoPIP-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No