Optimizing Drug Doses in Critically Ill

Optimizing Drug Doses to Improve Outcomes of Critically Ill Patients

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.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury; Kidney Functional
• Intervention / Treatment: Other: No Intervention

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

40 patients with traumatic brain injury requiring levetiracetam admitted to the University of North Carolina Intensive Care Unit and University of Kentucky Chandler Medical Center Intensive Care Unit

Description

Inclusion Criteria:

1. Adults ≥ 18 years
2. Patients with TBI requiring levetiracetam for seizure prophylaxis
3. Anticipated length of stay in the SICU or NSICU > 48 hours
4. Informed consent provided by the patient's designated medical proxy

Exclusion Criteria:

1. Pregnancy
2. Patients with renal dysfunction (CKD stages 3 - 5 and/or SCr > 1.4 mg/dL)
3. Patients receiving renal replacement therapy
4. Brain death or suspected imminent brain death within the next 48 hours
5. Patients with history of nephrectomy or renal transplant

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: University of Kentucky
• Investigators: Principal Investigator: Kathryn Morbitzer, PharmD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: April 29, 2015
• First Submitted That Met QC Criteria: May 5, 2015
• First Posted (Estimate): May 8, 2015

Study Record Updates

• Last Update Posted (Actual): June 20, 2017
• Last Update Submitted That Met QC Criteria: June 19, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: 15-0455