A Pharmacokinetic Analysis of Levetiracetam Prophylaxis in Critically Ill Patients With Severe Traumatic Brain Injury

NCT04836481 | Completed

• 1 other identifier: 2020-0744
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims is to describe the pharmacokinetic properties of levetiracetam through measurement of serum concentrations in critically ill, severe traumatic brain injury patients.

Conditions

Traumatic Brain Injury

Keywords

Levetiracetam; Seizure Prophylaxis; Pharmacokinetic

Outcome Measures

Primary Outcomes (5)

• Serum Levetiracetam Concentration 1

  Serum levetiracetam concentration collected at 0.5 hours after target dose for sampling

  Hour 0.5

• Serum Levetiracetam Concentration 2

  Serum levetiracetam concentration collected at hour 1 after target dose for sampling

  Hour 1

• Serum Levetiracetam Concentration 3

  Serum levetiracetam concentration collected at hour 4 after target dose for sampling

  Hour 4

• Serum Levetiracetam Concentration 4

  Serum levetiracetam concentration collected at hour 6 (patients receiving every 8 hour levetiracetam) or hour 8 (patients receiving every 12 hour levetiracetam)

  Hour 6-8

• Serum Levetiracetam Concentration 5

  Serum levetiracetam concentration collected at hour 8 (patients receiving every 8 hour levetiracetam) or hour 12 (patients receiving every 12 hour levetiracetam)

  Hour 8-12

Secondary Outcomes (10)

• Intracranial Pressure

  Baseline to Day 7

• Cerebral Perfusion Pressure

  Baseline to Day 7

• Pressure Reactivity Index

  Baseline to Day 7

• Cerebral Blood Flow

  Baseline to Day 7

• Cerebral Microdialysis Glucose Concentration

  Baseline to Day 7

Study Arms (2)

LEV8

Levetiracetam 1000 mg every 8 hours

Other: Serum Sample Collection

LEV12

Levetiracetam 1000 mg every 12 hours

Other: Serum Sample Collection

Interventions

Serum Sample Collection OTHER

Each patient will have 5 serum samples collected for analysis after a minimum six consecutive doses. Patients receiving LEV8 will have sampled collected at hours 0.5, 1, 4, 6, and 8. Patients receiving LEV12 will have sampled collected at hours 0.5, 1, 4, 8, and 12.

LEV12; LEV8

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The target population for this study will be patients with severe traumatic brain injury, defined as a post-resuscitation GCS 3-8 with or without CT abnormalities who are receiving intravenous levetiracetam 1000 mg every 8 or every 12 hours for seizure prophylaxis.

You may qualify if:

• Admitted to the neurosurgical intensive care unit or surgical intensive care unit following severe traumatic brain injury (post-resuscitation GCS 3-8 with or without CT abnormalities)
• Receiving intravenous levetiracetam for seizure prophylaxis at a dose of 1000 mg every 12 hours or 1000 mg every 8 hours at time of enrollment

You may not qualify if:

• Known history of epilepsy or seizure disorder
• Taking antiseizure medication prior to admission
• Taking medication with known effect on levetiracetam pharmacokinetics including carbamazepine, phenytoin, oxcarbazepine, mefloquine, methotrexate, mianserin, or orlistat
• Weight \< 50 kg
• Anticipated survival \<72 hours from injury, as deemed by the primary neurosurgical provider
• Acute Kidney Injury (Scr rise \> 0.3 mg/dL from baseline) or creatinine clearance \<50 mL/min at time of enrollment
• Prisoners
• Pregnant

Sponsors & Collaborators

• University of Cincinnati: lead
• American College of Clinical Pharmacy: collaborator

Study Sites (1)

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Related Publications (18)

• Cook AM, Hatton-Kolpek J. Augmented Renal Clearance. Pharmacotherapy. 2019 Mar;39(3):346-354. doi: 10.1002/phar.2231. Epub 2019 Mar 11.

  PMID: 30723936 BACKGROUND

• Rowe AS, Goodwin H, Brophy GM, Bushwitz J, Castle A, Deen D, Johnson D, Lesch C, Liang N, Potter E, Roels C, Samaan K, Rhoney DH; Neurocritical Care Society Pharmacy Section. Seizure prophylaxis in neurocritical care: a review of evidence-based support. Pharmacotherapy. 2014;34(4):396-409. doi: 10.1002/phar.1374. Epub 2013 Nov 26.

  PMID: 24277723 BACKGROUND

• Barletta JF, Mangram AJ, Byrne M, Sucher JF, Hollingworth AK, Ali-Osman FR, Shirah GR, Haley M, Dzandu JK. Identifying augmented renal clearance in trauma patients: Validation of the Augmented Renal Clearance in Trauma Intensive Care scoring system. J Trauma Acute Care Surg. 2017 Apr;82(4):665-671. doi: 10.1097/TA.0000000000001387.

  PMID: 28129261 BACKGROUND

• Zangbar B, Khalil M, Gruessner A, Joseph B, Friese R, Kulvatunyou N, Wynne J, Latifi R, Rhee P, O'Keeffe T. Levetiracetam Prophylaxis for Post-traumatic Brain Injury Seizures is Ineffective: A Propensity Score Analysis. World J Surg. 2016 Nov;40(11):2667-2672. doi: 10.1007/s00268-016-3606-y.

  PMID: 27307089 RESULT

• Gabriel WM, Rowe AS. Long-term comparison of GOS-E scores in patients treated with phenytoin or levetiracetam for posttraumatic seizure prophylaxis after traumatic brain injury. Ann Pharmacother. 2014 Nov;48(11):1440-4. doi: 10.1177/1060028014549013. Epub 2014 Aug 28.

  PMID: 25169249 RESULT

• Inaba K, Menaker J, Branco BC, Gooch J, Okoye OT, Herrold J, Scalea TM, Dubose J, Demetriades D. A prospective multicenter comparison of levetiracetam versus phenytoin for early posttraumatic seizure prophylaxis. J Trauma Acute Care Surg. 2013 Mar;74(3):766-71; discussion 771-3. doi: 10.1097/TA.0b013e3182826e84.

  PMID: 23425733 RESULT

• Jones KE, Puccio AM, Harshman KJ, Falcione B, Benedict N, Jankowitz BT, Stippler M, Fischer M, Sauber-Schatz EK, Fabio A, Darby JM, Okonkwo DO. Levetiracetam versus phenytoin for seizure prophylaxis in severe traumatic brain injury. Neurosurg Focus. 2008 Oct;25(4):E3. doi: 10.3171/FOC.2008.25.10.E3.

  PMID: 18828701 RESULT

• Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care. 2010 Apr;12(2):165-72. doi: 10.1007/s12028-009-9304-y.

  PMID: 19898966 RESULT

• Ramael S, Daoust A, Otoul C, Toublanc N, Troenaru M, Lu ZS, Stockis A. Levetiracetam intravenous infusion: a randomized, placebo-controlled safety and pharmacokinetic study. Epilepsia. 2006 Jul;47(7):1128-35. doi: 10.1111/j.1528-1167.2006.00586.x.

  PMID: 16886975 RESULT

• Steinhoff BJ, Staack AM. Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience. Ther Adv Neurol Disord. 2019 Sep 9;12:1756286419873518. doi: 10.1177/1756286419873518. eCollection 2019.

  PMID: 31523280 RESULT

• Spencer DD, Jacobi J, Juenke JM, Fleck JD, Kays MB. Steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care patients. Pharmacotherapy. 2011 Oct;31(10):934-41. doi: 10.1592/phco.31.10.934.

  PMID: 21950640 RESULT

• Cotta MO, Abdul-Aziz MH, Frey OR, Sime FB, Roberts JA, Roehr AC. What Are the Predictors for Achieving Therapeutic Levetiracetam Serum Concentrations in Adult Neurological Patients? Ther Drug Monit. 2020 Aug;42(4):626-630. doi: 10.1097/FTD.0000000000000731.

  PMID: 31977751 RESULT

• Klein P, Herr D, Pearl PL, Natale J, Levine Z, Nogay C, Sandoval F, Trzcinsky S, Atabaki SM, Tsuchida T, van den Anker J, Soldin SJ, He J, McCarter R. Results of phase II pharmacokinetic study of levetiracetam for prevention of post-traumatic epilepsy. Epilepsy Behav. 2012 Aug;24(4):457-61. doi: 10.1016/j.yebeh.2012.05.011. Epub 2012 Jul 7.

  PMID: 22771222 RESULT

• Uges JW, van Huizen MD, Engelsman J, Wilms EB, Touw DJ, Peeters E, Vecht CJ. Safety and pharmacokinetics of intravenous levetiracetam infusion as add-on in status epilepticus. Epilepsia. 2009 Mar;50(3):415-21. doi: 10.1111/j.1528-1167.2008.01889.x. Epub 2008 Nov 17.

  PMID: 19054418 RESULT

• Udy A, Boots R, Senthuran S, Stuart J, Deans R, Lassig-Smith M, Lipman J. Augmented creatinine clearance in traumatic brain injury. Anesth Analg. 2010 Dec;111(6):1505-10. doi: 10.1213/ANE.0b013e3181f7107d. Epub 2010 Nov 3.

  PMID: 21048095 RESULT

• May CC, Arora S, Parli SE, Fraser JF, Bastin MT, Cook AM. Augmented Renal Clearance in Patients with Subarachnoid Hemorrhage. Neurocrit Care. 2015 Dec;23(3):374-9. doi: 10.1007/s12028-015-0127-8.

  PMID: 25761425 RESULT

• Tong X, Patsalos PN. A microdialysis study of the novel antiepileptic drug levetiracetam: extracellular pharmacokinetics and effect on taurine in rat brain. Br J Pharmacol. 2001 Jul;133(6):867-74. doi: 10.1038/sj.bjp.0704141.

  PMID: 11454660 RESULT

• Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.

  PMID: 1244564 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum samples

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Sarah Schuman Harlan, PharmD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

• Shaun Keegan, PharmD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

• Carolyn Philpott, PharmD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pharmacy Resident, Primary Investigator

Study Record Dates

• First Submitted: December 10, 2020
• First Posted: April 8, 2021
• Study Start: January 1, 2021
• Primary Completion: May 1, 2022
• Study Completion: October 1, 2023
• Last Updated: February 29, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)