Clinical trial NCT00663403: Pharmacokinetics of Daptomycin in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis (CVVHD)
Official title: Pharmacokinetics of Daptomycin in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis (CVVHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Critically Ill
Hemodialysis
Keywords: daptomycin
pharmacokinetics
renal replacement therapy
critical illness
intensive care units
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
First posted: 2008-04-22
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

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.

Eligibility 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

Primary outcomes:
measure: Daptomycin Transmembrane Clearance by Continuous Venovenous Hemodialysis
timeFrame: From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis
Secondary outcomes:
measure: Daptomycin Dose Actually Administered
timeFrame: Time of daptomycin administration
measure: Observed Daptomycin Peak Serum Concentration
timeFrame: At the end of the daptomycin intravenous infusion (at approximately 30 minutes)
measure: Daptomycin Volume of Distribution at Steady State
timeFrame: From time of daptomycin administration to 48 hours post dose
measure: Daptomycin Total Body Clearance
timeFrame: From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis
measure: Daptomycin Half-life
timeFrame: From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis
measure: Daptomycin Free Fraction
timeFrame: From time of daptomycin administration to 48 hours post dose
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan University Hospital
state: Michigan
Study officials:
affiliation: University of Michigan, College of Pharmacy
name: Bruce A Mueller, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1097/CCM.0b013e3181fa36fb.