Optimizing Drug Doses in Critically Ill

Study Overview
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Brief Summary
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The primary objectives of this study are to examine whether augmented renal clearance (ARC) compromises renally eliminated drug therapeutic serum concentrations in patients with traumatic brain injury (TBI) and to estimate the optimal dose needed to achieve therapeutic serum concentrations of the probe medication levetiracetam in patients with TBI.

Detailed Description
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Purpose: The primary objectives of this study are to examine whether augmented renal clearance compromises renally eliminated drug therapeutic serum concentrations in patients with traumatic brain injury (TBI) and to estimate the optimal dose needed to achieve therapeutic serum concentrations of the probe medication levetiracetam in patients with TBI. Participants: The population will be comprised of patients with traumatic brain injury requiring levetiracetam for seizure prophylaxis admitted to the neurosciences intensive care unit Procedures (methods): This is a multi-center, prospective, non-randomized pharmacokinetic study in patients with TBI. In patients who meet the inclusion criteria, a 12-hour urine collection for measuring creatinine clearance levetiracetam urine concentrations will be performed daily for 7 days. Serum levetiracetam concentrations will be obtained twice daily for 7 days.

Official Title
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Optimizing Drug Doses to Improve Outcomes of Critically Ill Patients

Conditions
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Traumatic Brain Injury, Kidney Functional

Intervention / Treatment
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* Other: No Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥ 18 years Patients with TBI requiring levetiracetam for seizure prophylaxis Anticipated length of stay in the SICU or NSICU > 48 hours Informed consent provided by the patient's designated medical proxy Exclusion Criteria: Pregnancy Patients with renal dysfunction (CKD stages 3 - 5 and/or SCr > 1.4 mg/dL) Patients receiving renal replacement therapy Brain death or suspected imminent brain death within the next 48 hours Patients with history of nephrectomy or renal transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: No Intervention|No Intervention|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To examine whether ARC compromises renally eliminated drug therapeutic serum concentrations in patients with TBI (urine collections/ two levetiracetam serum concentrations, to measure creatinine clearance and therapeutic drug concentrations) |  | Daily 12-hour urine collections and two levetiracetam serum concentrations will be performed to directly measure creatinine clearance and therapeutic drug concentrations up to day 7 of ICU stay | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To estimate the optimal dose needed to achieve therapeutic serum concentrations of the probe medication levetiracetam in patients with TBI |  | Data will be obtained during study period of up to 7 days |