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

Hemodialysis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00663403
• Other study ID #: 063940
• Secondary ID: HUM00005646
• Status: Completed
• Phase: Phase 4
• First received: April 18, 2008
• Last updated: December 1, 2015
• Start date: February 2007
• Est. completion date: April 2009

Study information

• Verified date: May 2009
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Critical Illness
• Critically Ill
• Hemodialysis

Intervention

Drug:
• Daptomycin
Daptomcyin 8 mg/kg infused intravenously every 48 hours

Locations

Country	Name	City	State
United States	University of Michigan University Hospital	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	Cubist Pharmaceuticals LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Daptomycin Dose Actually Administered		Time of daptomycin administration	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No