Critically Ill, Hemodialysis
Conditions
Keywords
daptomycin, pharmacokinetics, renal replacement therapy, critical illness, intensive care units
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.
Interventions
DRUGDaptomycin
Daptomcyin 8 mg/kg infused intravenously every 48 hours
Sponsors
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
University of Michigan
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 Dose Actually Administered | Time of daptomycin administration | — |
| 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 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 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Daptomycin in Continuous Renal Replacement Therapy (CRRT) This is a single arm study. Critically ill study subjects receiving continuous venovenous hemodialysis and prescribed daptomycin will receive daptomycin 8 mg/kg IV every 48 hours. Serial serum and effluent samples will be collected over 48 hours to assess daptomycin transmembrane clearance and pharmacokinetics during continuous venovenous hemodialysis. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Daptomycin in Continuous Renal Replacement Therapy (CRRT) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 51 years STANDARD_DEVIATION 14 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Daptomycin Transmembrane Clearance by Continuous Venovenous Hemodialysis
Quantifies the rate of daptomcyin removal by continuous venovenous hemodialysis.
Time frame: From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daptomycin in Continuous Renal Replacement Therapy (CRRT) | Daptomycin Transmembrane Clearance by Continuous Venovenous Hemodialysis | 6.3 mL/min | Standard Deviation 2.9 |
Secondary
Daptomycin Dose Actually Administered
Time frame: Time of daptomycin administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daptomycin in Continuous Renal Replacement Therapy (CRRT) | Daptomycin Dose Actually Administered | 7.7 mg/kg | Standard Deviation 0.6 |
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.
Time frame: From time of daptomycin administration to 48 hours post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daptomycin in Continuous Renal Replacement Therapy (CRRT) | Daptomycin Free Fraction | 17.5 percent protein binding | Standard Deviation 5 |
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.
Time frame: From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daptomycin in Continuous Renal Replacement Therapy (CRRT) | Daptomycin Half-life | 20.8 hours | Standard Deviation 16.5 |
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.
Time frame: From time of daptomycin administration to 48 hours post dose when subjects were also receiving continuous venovenous hemodialysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daptomycin in Continuous Renal Replacement Therapy (CRRT) | Daptomycin Total Body Clearance | 0.13 mL/min/kg | Standard Deviation 0.04 |
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.
Time frame: From time of daptomycin administration to 48 hours post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daptomycin in Continuous Renal Replacement Therapy (CRRT) | Daptomycin Volume of Distribution at Steady State | 0.23 L/kg | Standard Deviation 0.14 |
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.
Time frame: At the end of the daptomycin intravenous infusion (at approximately 30 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daptomycin in Continuous Renal Replacement Therapy (CRRT) | Observed Daptomycin Peak Serum Concentration | 81.2 ug/mL | Standard Deviation 19 |