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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Late-Onset Neonatal Sepsis

Intervention / Treatment
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* Drug: Piperacillin/tazobactam


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 72 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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late-onset sepsis, piperacillin/tazobactam, model-based dose, empirical dose