Pharmacokinetics of Daptomycin in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis (CVVHD)

Phase 4

Completed

Conditions: Hemodialysis
Critically Ill

Registration Number: NCT00663403

Lead Sponsor: University of Michigan

Brief Summary: Daptomycin is an antibiotic that is affective against many strains of antibiotic resistant microorganisms. This antibiotic would be appropriate for use in the intensive care unit (ICU) considering the severity of illness and high risk for infection within this hospital environment. While in the ICU, patients may develop acute renal failure. Approximately 75% of ICU patients who develop acute renal failure will require some form of renal replacement therapy until their kidneys recover. Continuous hemodialysis is becoming one of the most common forms of dialysis in the ICU as it is a gentle type of dialysis provided over longer periods of time. The current data demonstrating the ability of continuous hemodialysis to remove daptomycin from the body is derived from in-vitro trials. The purpose of this trial is to determine the extent of daptomycin removal from critically ill patients receiving continuous hemodialysis. Findings from this trial will be used to develop new dosing recommendations for daptomycin in continuous hemodialysis.

Detailed Description: Daptomycin is a FDA approved antibiotic. This pharmacokinetic trial will monitor daptomycin drug concentrations during continuous hemodialysis. The daptomycin concentration profiles developed from this study will assist in developing a dose recommendation that will result in daptomycin levels that are safe and within therapeutic ranges, as previously identified, in critically ill patients with acute renal failure treated with continuous hemodialysis.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 8

Inclusion Criteria

=/> 18 years of age
Prescribed Continuous Venovenous Hemodialysis (CVVHD) as determined by the primary physician
Prescribed daptomycin as determined by the primary physician
Informed consent granted

Exclusion Criteria

< 18 years of age
Allergy to daptomycin
Patients being primarily treated with daptomycin for diagnosis of osteomyelitis, meningitis, or pneumonia without adequate concomitant use of other more effective antimicrobial agents as daptomycin is not indicated for primary treatment of these types of infections
Inability to complete 48 hours of Continuous Venovenous Hemodialysis (CVVHD)
Concurrent use of other extracorporeal therapies such as Extracorporeal Membrane Oxygenation (ECMO) or plasmapheresis and intermittent hemodialysis
Inability to obtain informed consent
Pregnant and/or breastfeeding women

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Daptomycin Transmembrane Clearance by Continuous Venovenous Hemodialysis	From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis	Quantifies the rate of daptomcyin removal by continuous venovenous hemodialysis.

Secondary Outcome Measures

Name	Time	Method
Daptomycin Free Fraction	From time of daptomycin administration to 48 hours post dose	In the body, daptomcyin may be bound to proteins in the blood or it may not be bound to any proteins (also as the "free" component.) Free fraction describes the percent of daptomycin that is unbound or free. The unbound portion of daptomycin is able to kill bacteria.
Daptomycin Dose Actually Administered	Time of daptomycin administration
Observed Daptomycin Peak Serum Concentration	At the end of the daptomycin intravenous infusion (at approximately 30 minutes)	The maximum concentration of daptomycin in the body after receiving a dose of the drug. This was determined at the end of the daptomycin intravenous infusion at approximately 30 min.
Daptomycin Volume of Distribution at Steady State	From time of daptomycin administration to 48 hours post dose	Volume of distribution quantifies the distribution of daptomycin between the blood and the rest of the body. The greater the volume of distribtion, the greater the extent of daptomycin distribution throughout the body.
Daptomycin Half-life	From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis	Half-life describes the time it takes for the concentration of the daptomycin in the body to decrease by one half.
Daptomycin Total Body Clearance	From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis	Total body clearance represents the rate at which daptomycin is removed from the body. In patients treated with continuous venovenous hemodialysis, the major pathways of daptomycin removal likely are: removal by continuuous venovenous hemodialysis (transmembrane clearance) and breakdown by the liver.