Target Site Pharmacokinetics of Ertapenem After Multiple Doses in Diabetes Patients With Soft Tissue Infection (2007-005020-33)

Background/rationale: Ertapenem is an innovative antimicrobial agent, which is approved in the European Union for diabetic foot infections of the skin and soft tissue. Although its antimicrobial spectrum and activity against ESBL-strains are promising to treat infected ulcers associated with diabetes, there is a lack of data on tissue pharmacokinetics of ertapenem in this patient population. However, for antimicrobial efficacy it is important to show that the antibiotic achieves sufficient concentrations at the site of infection, i.e. in tissue. A recent clinical study by Burkhardt et al. (Journal of Antimicrobial Chemotherapy, 2006) using the microdialysis technique showed that the free tissue concentrations after a single dose of 1 g ertapenem are sufficient and adequate to kill most relevant bacteria, suggesting efficacy of ertapenem for soft tissue infections. It is well known that there is no accumulation of ertapenem in plasma after multiple doses of 1 g every 24 h in patients without significantly impaired renal function. The single dose study by Burkhardt et al. also suggests that only negligible drug accumulation can be expected in soft tissues of healthy young volunteers after multiple doses. However, it was shown for other antibiotics that tissue PK may be significantly different under pathologic conditions, leading to impaired penetration, but subsequent accumulation after multiple doses due to a longer tissue half life than in healthy volunteers. Since the properties of inflamed tissue may diverge from those of healthy tissue it is important to evaluate which concentrations of ertapenem are reached in inflamed tissue after multiple doses.

Clinical study: In the present study we will measure the concentrations of ertapenem over time in plasma and infected tissue of 10 diabetes patients after multiple doses. The microdialysis technique will be used. The ertapenem concentrations will be measured in inflamed tissue and in non-inflamed subcutaneous tissue to identify the effect of inflammation on pharmacokinetics. The findings of the present study will help to confirm the efficacy of ertapenem for the indication of diabetic soft tissue infections.

Study Overview

• Status: Completed
• Conditions: Soft Tissue Infection
• Intervention / Treatment: Procedure: Microdialysis

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University Vienna, Department of Clinical Pharacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, aged between 18 and 85 years
• Diagnosis of Diabetes mellitus
• Clinically diagnosed skin or soft tissue infection and/or infected ulcers of the leg, requiring antimicrobial therapy
• Prescription of ertapenem for therapeutic reasons
• Willingness and ability to comply with the protocol
• Signed informed consent

Exclusion Criteria:

• HIV, Hepatitis B or C positive
• Allergy or hypersensitivity against study drug
• Severe renal impairment, defined by a serum creatinine level > 1.6 mg/L
• Pregnancy, or women of child bearing potential not willing to apply adequate contraception during study period
• Any disease considered relevant for proper performance of the study, or risks to the patient, at the discretion of the investigator

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics in tissue	3 years

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: April 4, 2008
• First Submitted That Met QC Criteria: April 14, 2008
• First Posted (Estimate): April 15, 2008

Study Record Updates

• Last Update Posted (Estimate): August 9, 2011
• Last Update Submitted That Met QC Criteria: August 8, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: ertapenem tissue PK
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Soft Tissue Infections
• Other Study ID Numbers: Erta_MD_1