Tissue Penetration of Ceftolozane/Tazobactam in Diabetic Patients With Lower Limb Infections

Diabetes Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02620774
• Other study ID #: Nicolau-53433
• Status: Completed
• Phase: Phase 1
• Start date: February 19, 2016
• Est. completion date: April 2017

Study information

• Verified date: October 2017
• Source: Hartford Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will determine the tissue penetration of ceftolozane/tazobactam (Zerbaxa, Merck & Co.), a novel β-lactam/β-lactamase combination antibiotic, into the extracellular, interstitial fluid of soft tissue in diabetic patients with lower limb wound infections. Penetration will be compared with a group of healthy volunteer control participants.

Description:

This study will enroll 10 patients with diabetes who are admitted with a lower limb wound infection and 6 healthy volunteer control participants. The study will take place in an inpatient unit at Hartford Hospital for all patients and in the Clinical Research Center at Hartford Hospital for all healthy volunteers. All participants will receive at least 3 doses of ceftolozane/tazobactam 1.5g every 8 hours. A microdialysis probe (Mdialysis Inc., N. Chelmsford MA) will be inserted into the subcutaneous soft tissue near the margin of the wound (patients) or in the thigh (healthy volunteers). The microdialysis probe is perfused with lactated Ringer's solution and samples are collected each hour for 8 hours after the final dose. A peripheral intravenous catheter will be inserted into an arm vein to collect blood samples simultaneously with microdialysis samples. Concentrations in tissue are compared with blood to determine percent penetration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Experimental: Type 1 or Type 2 diabetes and a mild to moderate (Grade 2 or 3) wound infection of the lower limb

• Active Comparator: Healthy Adult Volunteer

Exclusion Criteria:

All Participants:

• Less than 18 years of age

• History of hypersensitivity to ceftolozane/tazobactam, piperacillin/tazobactam, or any ß-lactam antibiotic

• History of hypersensitivity to lidocaine or lidocaine derivatives

• Females who are pregnant or breastfeeding

• Concomitant receipt of any ß-lactams antibiotic

• Concomitant receipt of probenecid

• Reduced kidney function defined as creatinine clearance of = 50 mL/min

• Any other reason felt by the investigator to potentially affect the outcomes of the study

Experimental Group Only:

• No palpable pedal pulses present

• Participants likely to require multiple surgical interventions during the study period, which therefore could affect placement of the microdialysis catheter

Active Comparator Group Only:

• Positive urine drug screen (cocaine, tetrahydrocannabinol, opiates, benzodiazepines, and amphetamines)

• History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of screening.

• Use of tobacco- or nicotine-containing products in excess of the equivalence of 5 cigarettes per day.

• Use of prescription or nonprescription drugs, vitamins, or dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, with the exception of acetaminophen at doses of = 1 g/day. Herbal supplements, hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone-releasing intrauterine devices (IUDs), postcoital contraceptive methods), and hormone replacement therapy must be discontinued at least 14 days prior to the first dose of study medication. Depo-Provera® must be discontinued at least 6 months prior to the first dose of study medication.

Related Conditions & MeSH terms

• Diabetes
• Healthy Volunteers
• Infection
• Wound Infection

Intervention

Drug:
• Ceftolozane/tazobactam
3 or more doses of ceftolozane/tazobactam intravenously administered over 60 minutes every 8 hours

Procedure:
• Microdialysis Catheter Insertion
A 20 kila-Dalton microdialysis probe (63 MD catheter; MDialysis Inc., N. Chelmsford, MA) will be inserted into the subcutaneous tissue at the margin of the wound (patient group) or in the thigh tissue (healthy volunteers). The probe will be left in place for the final dose and all tissue sampling procedures thereafter. This probe is perfused with a physiologic solution to collect interstitial fluid samples. The probe will then be removed after completion of sample collection.

Locations

Country	Name	City	State
United States	Hartford Hospital	Hartford	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Hartford Hospital	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ceftolozane Tissue Penetration	The ratio of ceftolozane tissue concentration area under the curve (AUC) to plasma concentrations AUC following the final (i.e., 3rd) ceftolozane/tazobactam dose.; Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. Plasma and dialysate concentrations were determined at hours 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours after the first dose for determination of ceftolozane AUC in blood and tissue.	16-24 hours
Primary	Tazobactam Tissue Penetration	The ratio of tazobactam tissue concentration area under the curve (AUC) to plasma concentration AUC following the final (3rd) ceftolozane/tazobactam dose.; Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. Plasma and dialysate concentrations were determined at hours 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours after the first dose for determination of tazobactam AUC in blood and tissue.	16-24 hours
Secondary	Ceftolozane Area Under the Curve (AUC) in Tissue	The ceftolozane AUC in tissue from 16 to 24 hours.; Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. Dialysate concentrations were determined at hours 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours after the first dose for determination of ceftolozane AUC.	16 to 24 hours post-dose
Secondary	Tazobactam AUC in Tissue	The tazobactam AUC in tissue over 16 to 24 hours; Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. Dialysate concentrations were determined at hours 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours after the first dose for determination of tazobactam AUC.	16 to 24 hours post-dose
Secondary	Ceftolozane Total Drug AUC in Plasma	The ceftolozane total drug AUC in plasma over 16 to 24 hours; Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. Plasma concentrations were determined at hours 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours after the first dose for determination of ceftolozane AUC.	16 to 24 hours post-dose
Secondary	Tazobactam Total Drug AUC in Plasma	The tazobactam total drug AUC in plasma over 16 to 24 hours; Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. Plasma concentrations were determined at hours 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours after the first dose for determination of tazobactam AUC.	16 to 24 hours post-dose
Secondary	Number of Participants With Adverse Events	Number of reported or documented adverse events recorded during participation in the study.	Duration of study (34 hours)