Augmented Renal Clearance in Neurocritical Care

NCT07410624 | Recruiting

• 1 other identifier: Pro00112754
• Study Type: observational
• Target: 512
• Locations: 2 countries
• Sites: 3

Brief Summary

Stroke, severe brain injury, uncontrolled seizures and brain infections are the most common life-threatening neurological illnesses in the world with an estimated combined annual hospital management cost of up to 44 billion dollars. Seizures and infections are common complications following acute neurological illnesses and contribute significantly to poor outcomes if not promptly treated with appropriately dosed anti-seizure medications and antibiotics, respectively. Limited research suggested that many of those patients present with a phenomenon called augmented renal clearance (ARC) or, in other words, enhanced kidney function. ARC may have a significant influence on how medications are removed from the body potentially resulting in insufficient doses and treatment failure. Therefore, patients with ARC require higher medication doses; however, ARC is largely undetected using kidney assessment methods currently used in practice. In addition, it is not clear how medications should be dosed in those with ARC. The majority of ARC research has not focused on patients with life-threatening neurological illnesses. Thus, clinicians are likely under-dosing vital medications in those patients, and completely unaware. There is an immediate need to address the gap in knowledge. Therefore, this research aims to characterize the phenomenon of ARC in patients with life-threatening neurological illnesses through identifying the frequency, duration, contributing factors and clinical impact of ARC. Adult patients admitted to the neurosciences intensive care unit for life-threatening neurological illnesses will be enrolled in the study. Urine and blood samples wil be collected from participants to determine the presence of ARC and identify its contributing factors. In addition, blood samples will be collected from participants treated with select antibiotics and anti-seizure medications to determine their concentration and propose dose adjustment in those with ARC. This research is expected to improve the care of patients with life-threatening neurological illnesses through efficient identification and monitoring of patients exhibiting ARC facilitating timely medication dosage optimization. Furthermore, recommendations of optimal doses of commonly used medications in patients with ARC would improve the likelihood of treatment success with potential to improve patients' health and wellbeing.

Conditions

TBI (Traumatic Brain Injury); Status Epilepticus; Bacterial Meningitis; Augmented Renal Clearance (ARC); Subarachnoid Hemorrhage, Aneurysmal; Ischemic Stroke; Intracerebral Hemorrhage

Keywords

traumatic brain injury; seizures; status epilepticus; bacterial meningitis; brain infections; neuro-ICU; augmented renal clearance (ARC); augmented kidney function; creatinine clearance; neurological injury; TBI; ARC; subarachnoid hemorrhage; ischemic stroke; antimicrobials

Outcome Measures

Primary Outcomes (2)

• CrCl Measurements

  Participants' CrCl will be measured using the 8-h urine collection method (8h urine collection method provides best representation of 24h CrCl and is less labor intensive). Once the patient is enrolled in the study, the first 8-hour urine collection will be obtained. Concurrent morning SCr will be collected and measured CrCl will be calculated

  During hospital admission from enrolment for 10 days or until discharge from ICU, whichever comes first.

• Drug Concentration Determination

  Enrolled subjects who are receiving any of the tested medications as part of their standard clinical care will have blood samples drawn to determine their plasma concentrations. Four blood samples will be drawn through an already established catheter (as part of standard ICU care) without further inconvenience to the patient.

  Sampling will occur during the hospital stay around a single drug dose after 2 to 3 days of consistent dosing to approach steady state concentration.

Study Arms (1)

Adult patients admitted to the Neuro-ICU with life-threatening neurological illness or injury

Adult patients admitted to the Neuroscience Intensive Care Unit at any of the participating centers with life-threatening neurological illnesses (intracerebral hemorrhage, subarachnoid hemorrhage, ischemic stroke, status epilepticus, meningitis and traumatic brain injury).

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients admitted to the Neurosciences ICU at the participating institutions for stroke (ischemic and hemorrhagic), traumatic brain injury (TBI), status epilepticus (SE) or bacterial meningitis.

You may qualify if:

• Age 18-85 years
• Admitted to ICU at one of the participating sites
• Diagnosis: SAH, TBI, ICH, meningitis, SE or ischemic stroke
• Provision of informed consent
• Foley catheter in place at time of consent (to facilitate urine collection)

You may not qualify if:

• Incarceration
• Anticipated ICU length of stay is \< 72 hours (insufficient time for monitoring)

Sponsors & Collaborators

• University of Alberta: lead
• University of Kentucky: collaborator
• Ohio State University: collaborator

Study Sites (3)

UK HealthCare

Lexington, Kentucky, 40536, United States

RECRUITING

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

University of Alberta Hospital

Edmonton, Alberta, T6G 2X8, Canada

RECRUITING

Related Publications (28)

• Udy AA, Baptista JP, Lim NL, et al. Augmented Renal Clearance in the ICU: Results of a Multicenter Observational Study of Renal Function in Critically Ill Patients With Normal Plasma Creatinine Concentrations. Crit Care Med 2014;42(3):520-527. (In English). DOI: 10.1097/Ccm.0000000000000029.

  BACKGROUND

• Markantonis SL, Agathokleous-Kioupaki E. Can two-, four- or eight-hour urine collections after voluntary voiding be used instead of twenty-four-hour collections for the estimation of creatinine clearance in healthy subjects? Pharm World Sci. 1998 Dec;20(6):258-63. doi: 10.1023/a:1008674625308.

  PMID: 9972527 BACKGROUND

• Barletta JF, Mangram AJ, Byrne M, et al. The importance of empiric antibiotic dosing in critically ill trauma patients: Are we under-dosing based on augmented renal clearance and inaccurate renal clearance estimates? Journal of Trauma and Acute Care Surgery 2016;81(6):1115-1120. DOI: //dx.doi.org/10.1097/TA.0000000000001211.

  BACKGROUND

• Baptista JP, Udy AA, Sousa E, et al. A comparison of estimates of glomerular filtration in critically ill patients with augmented renal clearance. Critical Care (London, England) 2011;15(3):R139. DOI: //dx.doi.org/10.1186/cc10262.

  BACKGROUND

• Baptista JP, Sousa E, Martins PJ, Pimentel JM. Augmented renal clearance in septic patients and implications for vancomycin optimisation. International journal of antimicrobial agents 2012;39(5):420-423. DOI: //dx.doi.org/10.1016/j.ijantimicag.2011.12.011.

  BACKGROUND

• Minkute R, Briedis V, Steponaviciute R, Vitkauskiene A, Maciulaitis R. Augmented renal clearance--an evolving risk factor to consider during the treatment with vancomycin. J Clin Pharm Ther 2013;38(6):462-7. DOI: 10.1111/jcpt.12088.

  BACKGROUND

• Lonsdale DO, Udy AA, Roberts JA, Lipman J. Antibacterial therapeutic drug monitoring in cerebrospinal fluid: difficulty in achieving adequate drug concentrations. J Neurosurg 2013;118:297-301. DOI: 10.3171/2012.10.JNS12883.

  BACKGROUND

• Carlier M, Carrette S, Roberts JA, et al. Meropenem and piperacillin/tazobactam prescribing in critically ill patients: does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used? Crit Care 2013;17(3):R84. DOI: 10.1186/cc12705.

  BACKGROUND

• Roberts JA, Paul SK, Akova M, et al. DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis 2014;58(8):1072-83. (In eng). DOI: 10.1093/cid/ciu027.

  BACKGROUND

• Carrie C, Bentejac M, Cottenceau V, et al. Association between augmented renal clearance and clinical failure of antibiotic treatment in brain-injured patients with ventilator-acquired pneumonia: A preliminary study. Anaesth Crit Care Pain Med 2018;37(1):35-41. DOI: 10.1016/j.accpm.2017.06.006.

  BACKGROUND

• Lautrette A, Phan T-N, Ouchchane L, et al. High creatinine clearance in critically ill patients with community-acquired acute infectious meningitis. BMC Nephrology 2012;13:124. DOI: 10.1186/1471-2369-13-124.

  BACKGROUND

• Morbitzer KA, Jordan JD, Dehne KA, Durr EA, Olm-Shipman CM, Rhoney DH. Enhanced Renal Clearance in Patients With Hemorrhagic Stroke. Crit Care Med 2019;47(6):800-808. DOI: 10.1097/CCM.0000000000003716.

  BACKGROUND

• Morbitzer KA, Rhoney DH, Dehne KA, Jordan JD. Enhanced renal clearance and impact on vancomycin pharmacokinetic parameters in patients with hemorrhagic stroke. J Intensive Care. 2019 Nov 21;7:51. doi: 10.1186/s40560-019-0408-y. eCollection 2019.

  PMID: 31832200 BACKGROUND

• Morbitzer KA, Jordan JD, Sullivan KA, Durr EA, Olm-Shipman CM, Rhoney DH. Vancomycin Pharmacokinetic Parameters in Patients with Hemorrhagic Stroke. Neurocrit Care. 2016 Oct;25(2):250-7. doi: 10.1007/s12028-016-0264-8.

  PMID: 26942732 BACKGROUND

• Udy A, Boots R, Senthuran S, et al. Augmented Creatinine Clearance in Traumatic Brain Injury. Anesthesia & Analgesia 2010;111(6) (https://journals.lww.com/anesthesia-analgesia/Fulltext/2010/12000/Augmented_Creatinine_Clea rance_in_Traumatic_Brain.27.aspx).

  BACKGROUND

• 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

• Cook AM, Arora S, Davis J, Pittman T. Augmented Renal Clearance of Vancomycin and Levetiracetam in a Traumatic Brain Injury Patient. Neurocritical Care 2013;19:210-214. DOI: 10.1007/s12028-013-9837-y.

  BACKGROUND

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

  BACKGROUND

• Mahmoud SH, Shen C. Augmented Renal Clearance in Critical Illness: An Important Consideration in Drug Dosing. Pharmaceutics. 2017 Sep 16;9(3):36. doi: 10.3390/pharmaceutics9030036.

  PMID: 28926966 BACKGROUND

• Hobbs AL, Shea KM, Roberts KM, Daley MJ. Implications of Augmented Renal Clearance on Drug Dosing in Critically Ill Patients: A Focus on Antibiotics. Pharmacotherapy 2015;35(11):1063-75. DOI: 10.1002/phar.1653.

  BACKGROUND

• Udy AA, Putt MT, Boots RJ, Lipman J. ARC--augmented renal clearance. Curr Pharm Biotechnol. 2011 Dec;12(12):2020-9. doi: 10.2174/138920111798808446.

  PMID: 21554215 BACKGROUND

• Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clinical pharmacokinetics 2010;49(1):1-16. DOI: 10.2165/11318140-000000000-00000.

  BACKGROUND

• Kramer AH, Bleck TP. Neurocritical care of patients with central nervous system infections. Curr Treat Options Neurol. 2008 May;10(3):201-11. doi: 10.1007/s11940-008-0022-0.

  PMID: 18579024 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

• Mahmoud SH, Buxton J. Seizures and Choice of Antiepileptic Drugs Following Subarachnoid Hemorrhage: A Review. Can J Neurol Sci 2017;44(6):643-653. DOI: 10.1017/cjn.2017.206.

  BACKGROUND

• Holmquist L, Russo CA, Elixhauser A. Meningitis-Related Hospitalizations in the United States, 2006. 2008 Jul. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb-. Statistical Brief #57. Available from http://www.ncbi.nlm.nih.gov/books/NBK56046/

  PMID: 21735578 BACKGROUND

• Wang G, Zhang Z, Ayala C, Dunet DO, Fang J, George MG. Costs of hospitalization for stroke patients aged 18-64 years in the United States. J Stroke Cerebrovasc Dis 2014;23(5):861-8. DOI: 10.1016/j.jstrokecerebrovasdis.2013.07.017.

  BACKGROUND

• Kortland LM, Knake S, Rosenow F, Strzelczyk A. Cost of status epilepticus: A systematic review. Seizure. 2015 Jan;24:17-20. doi: 10.1016/j.seizure.2014.11.003. Epub 2014 Nov 15.

  PMID: 25564314 BACKGROUND

Related Links

• Neuro-CPK Laboratory Website

MeSH Terms

Conditions

Brain Injuries, Traumatic; Status Epilepticus; Meningitis, Bacterial; Subarachnoid Hemorrhage; Ischemic Stroke; Cerebral Hemorrhage; Seizures; Trauma, Nervous System; AIDS-Related Complex

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Wounds and Injuries; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Central Nervous System Infections; Meningitis; Neuroinflammatory Diseases; Intracranial Hemorrhages; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Stroke; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Sherif H Mahmoud, BSc (Pharm), MSc, PhD, FNCS

  University of Alberta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sherif H Mahmoud, BSc (Pharm), MSc, PhD, FNCS

CONTACT

780.492.5364; smahmoud@ualberta.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2026
• First Posted: February 13, 2026
• Study Start: October 1, 2021
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (2)