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

NCT05413343 | Completed FDA Drug

• 1 other identifier: 2022-468
• Study Type: observational
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective observational study is conducted at the First Affiliated Hospital of Zhejiang University School of Medicine from June 1, 2021 to January 1, 2024. The study aims to characterize the population pharmacokinetics of ceftazidime (CAZ) and avibactam (AVI) in critically ill patients receiving ceftazidime-avibactam (CAZ-AVI), including patients with and without renal replacement therapy (RRT). Plasma concentrations of CAZ and AVI will be measured after the first-dose and steady-state administrations. Population pharmacokinetic and pharmacokinetic/pharmacodynamic target-attainment analyses will be performed to explore dosing strategies according to renal function and RRT status.

Conditions

Severe Sepsis; Carbapenem Resistant Bacterial Infection

Keywords

Severe sepsis; Ceftazidime-avibactam; Population pharmacokinetics (PPK); Pharmacokinetic (PK); Critically ill Patients; Pharmacodynamic (PD); Renal replacement therapy

Outcome Measures

Primary Outcomes (3)

• Plasma drug concentrations of CAZ and AVI after first-dose administration

  Plasma concentrations of CAZ and AVI will be measured after the first-dose infusion.

  0, 1, 2, 4, 6, and 8 hours after the first-dose infusion.

• Plasma drug concentrations of CAZ and AVI at steady state

  Plasma drug concentrations of CAZ and AVI will be measured after the steady-state infusion

  0, 1, 2, 4, 6, and 8 hours after the steady-state infusion.

• Population pharmacokinetic characterization and PK/PD-based dosing evaluation of CAZ-AVI

  Population pharmacokinetic models of ceftazidime and avibactam will be developed using plasma concentration and clinical data from critically ill patients. Pharmacokinetic/pharmacodynamic analyses will be performed to evaluate dosing regimens across different levels of renal function, including patients receiving renal replacement therapy (RRT).

  After completion of pharmacokinetic data collection

Secondary Outcomes (6)

• Microbiological clearance

  14 day after the onset of infection

• Infection-related mortality

  14 day after the onset of infection

• Treatment outcome

  14 day after the onset of infection

• all-cause mortality

  30 day after the onset of infection

• length of stay

  Day 1 is defined as the day of confirmed diagnosis, the duration from confirmed diagnosis to ICU discharge will be measured.

Interventions

Ceftazidime-avibactam DRUG

Critically ill adult patients (≥18 years) receiving intravenous CAZ-AVI for carbapenem-resistant organism (CRO) infections will be enrolled. Arterial blood samples (3 mL) will be collected at 0, 1, 2, 4, 6, and 8 hours after the first-dose and steady-state CAZ-AVI infusions for measurement of plasma CAZ and AVI concentrations.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will comprise critically ill adult patients receiving ceftazidime-avibactam (CAZ-AVI) for carbapenem-resistant organism (CRO) infections at the intensive care unit of the First Affiliated Hospital, Zhejiang University School of Medicine.

You may qualify if:

• Critically ill patients with severe sepsis(CRO infections) and treated with CAZ-AVI(culture-confirmed CRO susceptible to CAZ-AVI);
• Age ≥ 18 years;
• Expected ICU stay ≥48 hours.
• Hemoglobin \>70 g/L during the pharmacokinetic blood-sampling period；
• The patient or authorized persons agree and sign the informed consent.

You may not qualify if:

• Expected ICU stay \<48 hours.
• Pregnant woman.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital,College of Medicine,Zhejiang University

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Sepsis

Interventions

avibactam, ceftazidime drug combination

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• YongHong Xiao, PhD

  First Affiliated Hospital of Zhejiang University

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 30 Days
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2022
• First Posted: June 10, 2022
• Study Start: June 1, 2021
• Primary Completion: September 8, 2023
• Study Completion: December 20, 2023
• Last Updated: September 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)