Clinical Study on Monitoring the Plasma Concentration of Ceftazidime-Avibactam in Critically Ill Patients

A observational study is conducting at the First Affiliated Hospital of the Medical College of Zhejiang University from June 1, 2021 to January 1, 2024. Patients with severe sepsis and treatment with Ceftazidime-avibactam (CAZ-AVI) will be enrolled.

Blood samples at different time points: 0 hour, 2 hours, 4 hours, 6 hours, and 8 hours after the first time and the steady state concentration(more than 4 times drug administration) of drug administration will be collected to detect plasma drug concentrations of CAZ-AVI.

Study Overview

• Status: Active, not recruiting
• Conditions: Severe Sepsis
• Intervention / Treatment: Drug: Ceftazidime-avibactam

Detailed Description

The investigators will collect the blood samples at different time points: 0 hour, 2 hours, 4 hours, 6 hours, and 8 hours after the first time and the steady state concentration(more than 4 times drug administration) of drug administration from the patients receive treatment with CAZ-AVI to detect plasma drug concentrations of CAZ-AVI. The collected specimens will be stored in a refrigerator at 0-8 °C, centrifuges within 24 hours (4 °C, 4000 r/min, 10 min), and the supernatant will be collected in an EP tube and stored at -80°C until subsequent analysis. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) will be used to detect plasma drug concentrations of CAZ-AVI. According to the outcomes ,the investigators will characterize the population pharmacokinetics (PPK) of CAZ-AVI in critically ill patients and performed pharmacodynamic target attainment analyses to determine optimal dosing regimens for patients with and without continuous renal replacement therapy (CRRT).

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • the First Affiliated Hospital,College of Medicine,Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with severe sepsis and treatment with Ceftazidime-Avibactam in ICU of the First Affiliated Hospital of the Medical College of Zhejiang University from January 1, 2022 to September 30, 2022.

Description

Inclusion Criteria:

• Patients with severe sepsis and treated with ceftazidime avibactam
• Age ≥ 18 years
• The patient or authorized persons agree and sign the informed consent
• The patient's hemoglobin is greater than 70g/l during blood collection

Exclusion Criteria:

• The expected length of ICU stay less than 48 hours,
• Pregnant woman,
• The blood sample is hemolysis.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma drug concentrations of CAZ-AVI	Plasma drug concentrations of CAZ-AVI after the first time of drug administration	0 hour, 2 hours, 4 hours, 6 hours, and 8 hours after the first time of drug administration
Plasma drug concentrations of CAZ-AVI	Plasma drug concentrations of CAZ-AVI after the steady state concentration (more than 4 times drug administration) of drug administration	0 hour, 2 hours, 4 hours, 6 hours, and 8 hours after the steady state concentration (more than 4 times drug administration) of drug administration
A population pharmacokinetic (PopPK) model for CAZ-AVI and to propose an appropriate dosing regimen in Chinese critically ill patients.	By conducting pharmacokinetic and pharmacodynamic analysis on the plasma drug concentration data of patients receiving CAZ-AVI treatment in the intensive care unit, we aim to develop a population pharmacokinetic (PopPK) model for critically ill patients in China and to formulate an appropriate dosing regimen for critically ill patients with varying degrees of renal function, including those undergoing renal replacement therapy.	After obtaining the patient's plasma drug concentration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum albumin	The level of serum albumin on the day of the first time of drug administration	The day of the first time of drug administration
Serum albumin	The level of serum albumin on the day of the steady state concentration(more than 4 times drug administration) of drug administration	The day of the steady state concentration (more than 4 times drug administration) of drug administration
The level of creatinine	The level of creatinine on the day of the first time of drug administration	The day of the first time of drug administration
The level of creatinine	The level of creatinine on the day of the steady state concentration(more than 4 times drug administration) of drug administration	The day of the first time of the steady state concentration (more than 4 times drug administration) of drug administration
The level of glomerular filtration rate	The level of glomerular filtration rate on the day of the first time of drug administration	The day of the first time of drug administration
The level of glomerular filtration rate	The level of glomerular filtration rate on the day of the steady state concentration (more than 4 times drug administration) of drug administration	The day of the steady state concentration (more than 4 times drug administration) of drug administration
Whether received renal replacement therapy	Whether the patient received renal replacement therapy on the day of the first time of drug administration, and the results are recorded in the form of categorical variables,(e.g.,yes or no).	The day of the first time of drug administration
Whether received renal replacement therapy	Whether the patient received renal replacement therapy on the day of the steady state concentration (more than 4 times drug administration) of drug administration, and the results are recorded in the form of categorical variables,(e.g.,yes or no).	The day of the steady state concentration (more than 4 times drug administration) of drug administration
Respiratory function	Whether the patient received mechanical ventilation on the day of the first time of drug administration, and the results are recorded in the form of categorical variables,(e.g.,yes or no).	The day of the first time of administration
Respiratory function	Whether the patient received mechanical ventilation on the day of the steady state concentration (more than 4 times drug administration) of drug administration, and the results are recorded in the form of categorical variables,(e.g.,yes or no).	The day of the steady state concentration (more than 4 times drug administration) of drug administration
Cardiovascular function	Whether the patient received vasoactive agents(including norepinephrine, epinephrine, dobutamine, and metarylamine), and the results are recorded in the form of categorical variables,(e.g.,yes or no).	The day of the first time of drug administration
Cardiovascular function	Whether the patient received vasoactive agents(including norepinephrine, epinephrine, dobutamine, and metarylamine), and the results are recorded in the form of categorical variables,(e.g.,yes or no).	The day of the steady state concentration (more than 4 times drug administration) of drug administration
CRRT treatment dosage	The specific parameters for patients undergoing CRRT include the type of CRRT machine, treatment modality, treatment method, filter type, treatment duration, pre-dilution volume, post-dilution volume, blood pump flow rate, dialysis pump flow rate, average hourly fluid removal, treatment dose, ultrafiltration rate, and waste fluid volume	The day of the first time of drug administration
CRRT treatment dosage	The specific parameters for patients undergoing CRRT include the type of CRRT machine, treatment modality, treatment method, filter type, treatment duration, pre-dilution volume, post-dilution volume, blood pump flow rate, dialysis pump flow rate, average hourly fluid removal, treatment dose, ultrafiltration rate, and waste fluid volume	The day of the steady state concentration (more than 4 times drug administration) of drug administration
microbiological clearance, infection-related mortality	microbiological clearance, 14 day infection-related mortality,	14 day after the onset of infection
all-cause mortality	30 day all-cause mortality,90 day all-cause mortality	30 day and 90 day after the onset of infection
length of stay	Post-infection ICU length of stay	Day 1 is defined as the day of confirmed diagnosis, the duration from confirmed diagnosis to ICU discharge will be measured.
length of stay	Total ICU length of stay.	From ICU admission to ICU discharge will be measured(assessed up to 120 days).

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Investigators: Study Chair: YongHong Xiao, PhD, First affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: June 7, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 10, 2022

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Severe sepsis; Ceftazidime-avibactam; Pharmacokinetic (PK); Critically ill Patients; Pharmacodynamic (PD); Plasma drug concentration; Population pharmacokinetics (PPK)
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Critical Illness; Sepsis; Third Generation Cephalosporins; Beta Lactam Antibiotics; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; beta-Lactamase Inhibitors; Avibactam, ceftazidime drug combination; Avibactam; Ceftazidime
• Other Study ID Numbers: 2022-468

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Respect ethics and protect patient privacy

Drug and device information, study documents

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