A Study of Avycaz (Ceftazidime/Avibactam) Pharmacokinetics/Pharmacodynamics (PK/PD) in Critically Ill Patients

Phase 1

Completed

• Conditions: Pharmacokinetics of Avycaz in ICU Patients
• Interventions: Drug: Ceftazidime/avibactam

• Registration Number: NCT02822950
• Lead Sponsor: Michigan State University

Brief Summary

The purpose of this study is to analyze the PK/PD of AvyCaz in critically ill patients in the Intensive Care Unit (12). This study will include medical and post-surgical patients who develop an infection where Avycaz can be utilized. Since these patients will have variable PK parameters, the investigators will also analyze (time-kill) these serum concentrations (ex vivo) against relevant clinical isolates (e.g. GNR with ESBL or KPC) from the ICU to determine microbiologic activity of Avycaz in critically ill patients with variable characteristics. Monte-Carlo simulations will also be conducted against clinical ICU isolates (JMI labs) to help determine appropriate dosing schedules based upon these PK parameters.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-06-28
• Study First Submitted QC: 2016-07-05
• Study First Posted: 2016-07-06
• Study Start: 2017-01
• Primary Completion: 2017-12
• Study Completion: 2017-12
• Results First Submitted: 2018-03-26
• Status Verified: 2018-11
• Results First Submitted QC: 2018-11-09
• Last Update Submitted: 2018-11-09
• Results First Posted: 2019-03-06
• Last Update Posted: 2019-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Adult (≥18y/o) patients with a medical or post-surgical infection such as skin/soft tissue infections, urinary infections, IA infections and pneumonia (including VAP)
• Patients requiring intensive care (critically ill patients) in the med/surg ICU (APACHE II score ≥ 15)
• Patients prescribed Avycaz for their infection will receive FDA recommended dosages and times of administration
• Written informed consent

Exclusion Criteria

• Pregnant Patients, patients older than 90 y/o, those with CrCl < 30 mL/min, patients with a BMI > 45 Kg/m2, patients unable to provide serum samples, and those with the risk of imminent death during the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ceftazadime/avibactam	Ceftazidime/avibactam	Ceftazadime/avibactam 2500 mg (1250 mg for CrCl 31-50 mL/min) IV over 120 minutes, every 8 hours \[other antibiotics can also be administered as needed\]. Patients will receive at least 3 doses (steady-state) of Avycaz prior to obtaining serum samples.

Primary Outcome Measures

Name	Time	Method
Mean (SD) Ceftazadime/Avibactam Pharmacokinetic (PK) Volume of Distribution Parameter in Intensive Care Patients	2,4,6, 8 hours after receiving the drug
Mean (SD) Ceftazadime/Avibactam Pharmacokinetic Half Life Parameter in Intensive Care Patients	2,4,6, 8 hours after receiving the drug
Mean (SD) Ceftazadime/Avibactam Pharmacokinetic Clearance of Drug Parameter in Intensive Care Patients	2,4,6, 8 hours after receiving the drug
Mean (SD) Ceftazadime/Avibactam Pharmacokinetic Area Under Serum Curve (mg*h/L) Parameter in Intensive Care Patients	2,4,6, 8 hours after receiving the drug
Mean (SD) Ceftazadime/Avibactam Pharmacokinetic (PK) Maximum Serum Concentration in Intensive Care Patients	2,4,6, 8 hours after receiving the drug