Pharmacokinetics of Ceftazidime-avibactam Among Critically-ill Patients Receiving CVVHDF

Pharmacokinetics of Ceftazidime-avibactam Among Critically-ill Patients Receiving Continuous Venovenous Hemodiafiltration

Ceftazidime-avibactam is used for treatment of invasive Gram-negative bacterial infections among critically ill patients, including those on continuous venovenous hemodiafiltration . However, dosing of ceftazidime-avibactam for these patients remains undefined. The purpose of this study was to evaluate the pharmacokinetics of ceftazidime and avibactam among critically-ill patients, including those receiving CVVHD. This is a registration of Dr. Shields' exempt project under IRB approved research study STUDY19040363

Study Overview

• Status: Completed
• Conditions: Bacterial Infections
• Intervention / Treatment: Drug: Ceftazidime-avibactam

Detailed Description

Patients who received ceftazidime-avibactam as part of their clinical care were consented. EMR data was collected as well as PK sampling around their dosing to include the following samples immediately pre-dose, then at the following times thereafter: 1, 2, 4, 6, and 8 hours. Blood samples were collected in lithium-heparin tubes from a central venous catheter that is not being used for the continuous venovenous hemodiafiltration. The tubes were centrifuged at 2500 rpm for 10 minutes within 1 hour from collection and the samples will be frozen at 80°C. The total concentrations of ceftazidime and avibactam were determined simultaneously from plasma by using a validated HPLC-tandem MS assay. Noncompartmental pharmacokinetics were calculated using the linear-up and logarithmic-down trapezoidal method, based on the assumption of first-order elimination.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Adult patients with confirmed or presumed invasive bacterial infections

Description

Inclusion Criteria:

• Adult patients receiving ceftazidime-avibactam as standard care

Exclusion Criteria:

• Less than 18 years-old

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
invasive bacterial infections; patients who are receiving Ceftazidime-avibactam are asked to provide blood samples around a dosing of the medication for analysis of samples	Drug: Ceftazidime-avibactam; collection of blood samples around clinical dosing immediately pre-dose, then at the following times thereafter: 1, 2, 4, 6, 8, and 12 hours and EMR review.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Levels of Ceftazidime and Avibactam Among Critically-ill Patients	PK samples obtained around standard of care dosing regimens immediately before and at 1, 2, 4, 6, and 8 hours after administration	8 hours

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: Allergan
• Investigators: Principal Investigator: Ryan Shields, Pharm D, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: April 20, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): September 29, 2020
• Last Update Submitted That Met QC Criteria: September 7, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Avibactam; Ceftazidime; Avibactam, ceftazidime drug combination
• Other Study ID Numbers: I# 0058410

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified data will be shared through peer-reviewed publication
• IPD Sharing Time Frame: Within 1 year of study completion
• IPD Sharing Access Criteria: will be on clinicaltrials.gov
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No