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

Sponsor

Shandong University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05981079

Collaborator

Shandong Provincial Hospital (Other), Qianfoshan Hospital (Other), Jinan Maternity and Child Care Hospital (Other), Yantai Yuhuangding Hospital (Other), Hebei Petro China Center Hospital (Other), Shengli Oilfield Hospital (Other), Liaocheng People's Hospital (Other), Jining Medical University (Other), W.F. Maternal and Child Health Hospital (Other), Taian City Central Hospital (Other)

332

Enrollment

Locations

Arms

Anticipated Duration (Months)

33.2

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Late-Onset Neonatal Sepsis	Drug: Piperacillin/tazobactam	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

332 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Actual Study Start Date :

Jul 31, 2023

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

May 31, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Successful outcome [At the follow-up visit (10 ± 1 days after the end of actual piperacillin/tazobactam therapy )]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

72 Hours and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	Shengli Oilfield Hospital	Dongying	China
2	Jinan Maternity and Child Care Hospital	Jinan	China
3	Qianfoshan Hospital	Jinan	China
4	Shandong Provincial Hospital	Jinan	China
5	Jining Medical University	Jining	China
6	Hebei Petro China Center Hospital	Langfang	China
7	Liaocheng People's Hospital	Liaocheng	China
8	Taian City Central Hospital	Tai'an	China
9	W.F. Maternal and Child Health Hospital	Weifang	China
10	Yantai Yuhuangding Hospital	Yantai	China