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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Critically Ill, Hemodialysis

Intervention / Treatment
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* Drug: Daptomycin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Daptomycin|Daptomcyin 8 mg/kg infused intravenously every 48 hours|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daptomycin Dose Actually Administered |  | Time of daptomycin administration | 
| Observed Daptomycin Peak Serum Concentration | 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. | At the end of the daptomycin intravenous infusion (at approximately 30 minutes) | 
| Daptomycin Volume of Distribution at Steady State | 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. | From time of daptomycin administration to 48 hours post dose | 
| Daptomycin Total Body Clearance | 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. | From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis | 
| Daptomycin Half-life | Half-life describes the time it takes for the concentration of the daptomycin in the body to decrease by one half. | From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis | 
| Daptomycin Free Fraction | 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. | From time of daptomycin administration to 48 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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daptomycin, pharmacokinetics, renal replacement therapy, critical illness, intensive care units