Acute Kidney Failure
Conditions
Keywords
ertapenem, continuous hemodialysis, pharmacokinetics
Brief summary
Critically ill patients in the intensive care unit often receive continuous hemodialysis to treat their kidney failure. Ertapenem is an antibiotic often used in these patients. Continuous dialysis may remove ertapenem, putting patients at risk for inappropriate treatment of their infection. This study will determine how much ertapenem is removed by continuous hemodialysis.
Detailed description
Subjects receiving CVVHD will receive a one gram dose of ertapenem. Serial blood samples over 24 hours will be taken to assess the ertapenem blood concentrations over time. Spent dialysate and urine samples (if any) will also be measured for ertapenem content to determine how much drug is removed by CVVHD and kidneys. A pharmacokinetic evaluation will be made to determine what is the most appropriate dose for this drug in patients receiving CVVHD to achieve pharmacokinetic and pharmacodynamic goals.
Interventions
DRUGertapenem
One gram ertapenem will be infused intravenously in subjects receiving continuous hemodialysis (CVVHD). Pharmacokinetic sampling in this study will occur with the first dose of ertapenem. While on CVVHD, enrolled subjects will receive ertapenem 1 g intravenously administered over 30 minutes. Two blood samples (5 mL each) will be collected from the arterial (pre-diafilter) port of the CVVHD tubing at time 0 (baseline), ½ hour (end of infusion), 1, 1½, 2, 3, 6, 12, and 24 hours. Effluent (5 mL) will also be collected at these predefined time points from the effluent port of the CVVHD tubing. If ertapenem is discontinued after the first dose then additional samples will be collected at 36 and 48 hours, otherwise ertapenem will be administered as soon as the 24 hour sample is obtained.
Sponsors
University of Michigan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hospitalized in ICU * Receiving Continuous hemodialysis * Prescribed ertapenem * Informed consent granted
Exclusion criteria
* \< 18 years of age * Allergy to ertapenem or other carbapenem antibiotic * Severe, life-threatening reaction to penicillin or cephalosporins * Patients experiencing or with history of CNS disorders (eg: seizure, stroke) * Patients experiencing CNS infection * Inability to complete 24 hours of CVVHD * Concurrent use of other extracorporeal therapies such as extracorporeal membrane oxygenation, plasmapheresis or intermittent hemodialysis * Inability to obtain informed consent * Pregnant and/or breastfeeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ertapenem Transmembrane Clearance by Continuous Hemodialysis. | 24 hours after receiving first 1 gram dose |
Countries
United States
Participant flow
Recruitment details
Subjects were consented and enrolled between April 2009 and March 2011. All subjects were patients receiving care in an intensive care unit at University of Michigan Health System.
Pre-assignment details
All patients that qualified for the study were approached. All subjects that gave their consent were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Ertapenem Subjects will receive ertapenem while receiving CVVHD
ertapenem : One gram ertapenem will be infused intravenously in subjects receiving continuous hemodialysis (CVVHD). Pharmacokinetic sampling in this study will occur with the first dose of ertapenem. While on CVVHD, enrolled subjects will receive ertapenem 1 g intravenously administered over 30 minutes. Two blood samples (5 mL each) will be collected from the arterial (pre-diafilter) port of the CVVHD tubing at time 0 (baseline), ½ hour (end of infusion), 1, 1½, 2, 3, 6, 12, and 24 hours. Effluent (5 mL) will also be collected at these predefined time points from the effluent port of the CVVHD tubing. If ertapenem is discontinued after the first dose then additional samples will be collected at 36 and 48 hours, otherwise ertapenem will be administered as soon as the 24 hour sample is obtained. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Ertapenem |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age Continuous | 62 years STANDARD_DEVIATION 16 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 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
Ertapenem Transmembrane Clearance by Continuous Hemodialysis.
Time frame: 24 hours after receiving first 1 gram dose
Population: All participants were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ertapenem | Ertapenem Transmembrane Clearance by Continuous Hemodialysis. | 10.4 mL/min | Standard Deviation 4.2 |