Pharmacokinetics of Daptomycin in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis (CVVHD) - Full Text View

Sponsor:	University of Michigan
Collaborator:	Cubist Pharmaceuticals
Information provided by:	University of Michigan
ClinicalTrials.gov Identifier:	NCT00663403

Purpose

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.

Condition	Intervention	Phase
Critically Ill Hemodialysis	Drug: Daptomycin	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label
Official Title:	Pharmacokinetics of Daptomycin in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis (CVVHD)

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics Dialysis

Drug Information available for: Daptomycin

U.S. FDA Resources

Further study details as provided by University of Michigan:

Primary Outcome Measures:

Daptomycin Transmembrane Clearance by Continuous Venovenous Hemodialysis [ Time Frame: From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis ] [ Designated as safety issue: No ]
Quantifies the rate of daptomcyin removal by continuous venovenous hemodialysis.

Secondary Outcome Measures:

Daptomycin Dose Actually Administered [ Time Frame: Time of daptomycin administration ] [ Designated as safety issue: No ]
Observed Daptomycin Peak Serum Concentration [ Time Frame: At the end of the daptomycin intravenous infusion (at approximately 30 minutes) ] [ Designated as safety issue: No ]
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 [ Time Frame: From time of daptomycin administration to 48 hours post dose ] [ Designated as safety issue: No ]
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 Total Body Clearance [ Time Frame: From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis ] [ Designated as safety issue: No ]
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.
Daptomycin Half-life [ Time Frame: From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis ] [ Designated as safety issue: No ]
Half-life describes the time it takes for the concentration of the daptomycin in the body to decrease by one half.
Daptomycin Free Fraction [ Time Frame: From time of daptomycin administration to 48 hours post dose ] [ Designated as safety issue: No ]
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.

Enrollment:	8
Study Start Date:	February 2007
Study Completion Date:	April 2009
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Intervention Details:

Daptomcyin 8 mg/kg infused intravenously every 48 hours

Other Name: Cubicin

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00663403

Locations

United States, Michigan
University of Michigan University Hospital
Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan

Cubist Pharmaceuticals

Investigators

Principal Investigator:

Bruce A Mueller, PharmD

University of Michigan, College of Pharmacy

More Information

No publications provided by University of Michigan

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vilay AM, Grio M, Depestel DD, Sowinski KM, Gao L, Heung M, Salama NN, Mueller BA. Daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis. Crit Care Med. 2011 Jan;39(1):19-25.

Responsible Party:	Bruce A. Mueller, University of Michigan, College of Pharmacy
ClinicalTrials.gov Identifier:	NCT00663403 History of Changes
Other Study ID Numbers:	063940, HUM00005646
Study First Received:	April 18, 2008
Results First Received:	April 29, 2010
Last Updated:	August 27, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Michigan:

daptomycin
pharmacokinetics
renal replacement therapy
critical illness
intensive care units

Additional relevant MeSH terms:

Critical Illness
Disease Attributes
Pathologic Processes
Daptomycin

Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2012