Pharmacokinetics of Ceftolozane/Tazobactam in Patients With Burns

This study will help provide information about how patients with burn handle two antibiotics (ceftolozane and tazobactam) and use that information to guide dosing recommendations for these patients. The 12 patients who complete the study will receive a single dose of 3 grams ceftolozane/tazobactam intravenously. We will collect blood and urine samples to determine how much of each antibiotic is in the body and urine at various times over a 24 hour period. This information will be used with previously published information from microbiology laboratories to perform simulations that will provide recommendations on optimal dosing recommendations of these antibiotics in patients with burns.

Study Overview

• Status: Terminated
• Conditions: Burns; Pharmacokinetics
• Intervention / Treatment: Drug: Ceftolozane/tazobactam

Detailed Description

A single dose pharmacokinetic study of ceftolozane and tazobactam will be conducted in patients with burns at the Burn Center at University Medical Center. A total of 12 adults aged 18 to 80 years with >/= 20% percent total body surface area burned will be required to complete the study. A single intravenous dose of ceftolozane and tazobactam of 2 grams/1 gram will be administered over 60 minutes and whole blood will be obtained predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours following the start of infusion. Urine samples (5 ml) will be collected from a urine collection bag (if the patient has urinated) at the following timepoints: 0-0.5, 0.5-1, 1-2, 2-4, 4-8, 8-12, and 12-24 hours for analysis of ceftolozane and tazobactam content. Urine for collected during each time period will be measured to determine urine volume for urine clearance calculations. The volume of urine in the urine over the entire 24 hour period and an aliquot sent for analysis of urine creatinine content to determine the patient's 24 hour creatinine clearance.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Lubbock, Texas, United States, 79415
      • University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female subjects, ages 18-80 years, of all racial and ethnic origins.
2. Non-English Spanish speakers will be included in the study.
3. We are recruiting 12 patients with thermal burn injuries (percent total body surface area burned >/= 20%). Patients will be at least five days from the date of the burn injury.
4. Patients will have central venous or arterial line access.
5. Patients will be already be receiving standard of care antimicrobial therapy for a suspected infection.

Exclusion Criteria:

1. Pregnant or nursing or unwilling to use a reliable contraception method during the study. The effects of ceftolozane and tazobactam on pregnancy are unknown. In addition, the metabolic changes that accompany pregnancy may alter the concentration-time profile of ceftolozane and tazobactam, so that the pregnancy and post-partum state would be a confounding variable.
2. Abnormal liver function tests: transaminases >10 times upper limit of normal, Alkaline phosphatase >5 times upper limit of normal, total bilirubin >5 times upper limit of normal.
3. History of allergies to beta-lactam antibiotics.
4. Patients unwilling to comply with study procedures.
5. Current or previous participation within 28 days of enrollment in another research study that involves the use of medication, contrast, or any other compound that may alter blood count and/or blood chemistry (liver function, kidney function or electrolyte balance), unless waved by principal investigator (PI).
6. Donation of 450mL (one unit) of blood or more within 8 weeks (56 days) prior to study enrollment, unless waved by PI.
7. Creatinine clearance < 30 ml/min as estimated by the Cockcroft-Gault equation.
8. Patients who are receiving piperazillin/tazobactam or have received piperacillin/tazobactam within the past 48 hours.
9. Patients who are receiving vasopressors.
10. Patients with a total body weight < 60 kg or > 130 kg.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ceftolozane/tazobactam; One dose of 3 grams ceftolozane/tazobactam will be administered to each study participant.	Drug: Ceftolozane/tazobactam; Single dose of 2 grams/1 gram intravenously administered over 60 minutes.; Other Names: Zerbaxa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ceftolozane Clearnace	Liters/hour (continuous values)	24 hours

Collaborators and Investigators

• Sponsor: Texas Tech University Health Sciences Center
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Ronald G Hall, PharmD, Texas Tech University HSC

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2017
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: December 21, 2016
• First Submitted That Met QC Criteria: December 21, 2016
• First Posted (Estimate): December 23, 2016

Study Record Updates

• Last Update Posted (Actual): March 2, 2021
• Last Update Submitted That Met QC Criteria: March 1, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: ceftolozane; tazobactam
• Additional Relevant MeSH Terms: Wounds and Injuries; Burns; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Tazobactam; Ceftolozane; Ceftolozane, tazobactam drug combination
• Other Study ID Numbers: 070619

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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.: Yes