ClinicalTrials.gg
RecruitingNCT07410624Neuro-ARCUpdated Feb 18, 2026

Augmented Renal Clearance in Neurocritical Care

An observational study in TBI (Traumatic Brain Injury), Status Epilepticus and Bacterial Meningitis, sponsored by University of Alberta. Recruiting at 3 sites in 2 countries. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2026-02-18.

Sponsored by University of Alberta · Observational

From the registry’s dates

  • Started Oct 2021; still recruiting 5 years 1 month later.
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
512
Ages
18 Years to 85 Years
Sex
All
01

Study 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.

Read the detailed description

Background and Importance: Stroke, severe brain injury, status epilepticus and meningitis 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 antiseizure medications (ASMs) and antimicrobials, respectively. Limited evidence suggests that augmented renal clearance (ARC) is present in many of those patients. Defined as a creatinine clearance (CrCl) > 130 ml/min/m2, the prevalence of ARC has been reported as high as 80%. ARC has a significant impact on clearance of renally eliminated drugs including some ASMs and antimicrobials, potentially resulting in low exposure with subsequent therapy failure. Therefore, patients with ARC require higher drug doses; however, ARC is largely undetected using the common CrCl equations and it is not clear how drugs should be dosed. The majority of ARC literature has not focused on neurocritical care patients; thus, clinicians are likely under-dosing vital medications in these patients and completely unaware. There is an immediate need to address the gap in knowledge.

The overall goal is to characterize the phenomenon of ARC in patients with life-threatening neurological illnesses in order to create a guide to clinicians regarding identification, monitoring and drug dosing in patients exhibiting ARC to facilitate treatment success.

Research Aims:

  1. To characterize the phenomenon of ARC in neurocritical care population (prevalence, duration and impact on hospital outcomes).
  2. To measure the impact of ARC on the disposition of commonly used renally eliminated medications in neurocritical care.
  3. To develop guidelines to clinicians regarding the identification, monitoring and drug dosing in neurocritical care patients exhibiting ARC (Knowledge Translation).

Methods/Approaches/Expertise: This will be a multicenter prospective observational study in adult patients admitted to the Neuroscience Intensive Care Units (ICU) for acute neurological illnesses. Participants' CrCl will be measured using the 8-h urine collection method daily for 10 days or until ICU discharge. Participants with a urine CrCl > 130 ml/min/m2 will be included in the ARC group. Regression modeling will be utilized to determine predictors of ARC and propose an ARC prediction model. In addition, patients treated with levetiracetam, lacosamide, vancomycin, meropenem, cefepime or piperacillin-tazobactam will have blood samples collected for plasma concentration determination. Pharmacokinetic parameters will be calculated and dosage regimens will be proposed.

This work will be a collaborative effort among investigators with diverse expertise in pharmacokinetics, critical care and clinical research.

Expected Outcomes: 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 patient outcomes.

02

Conditions studied

  • 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
03

In context

Brain Injuries, Traumatic

1,721 studies on the registry are indexed under Brain Injuries, Traumatic; 447 are open to participants now.

This study's planned enrollment of 512 is above the median of 117 across 557 observational studies indexed under Brain Injuries, Traumatic.

Browse Brain Injuries, Traumatic studies →

Lead sponsor

University of Alberta is the lead sponsor of 823 studies on the registry; 169 are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 3 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No
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.

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

  1. Incarceration
  2. Anticipated ICU length of stay is \< 72 hours (insufficient time for monitoring)
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
512 participants (estimated)
Patient registry
No

Groups and cohorts

  • 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).

06

What researchers measure

Primary outcomes

  1. 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

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

  2. 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.

    Time frame: 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.

07

Study locations

3 of 3 sites recruiting
08

References and documents

Publications

  • Udy AA, Baptista JP, Lim NL, Joynt GM, Jarrett P, Wockner L, Boots RJ, Lipman J. 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 Mar;42(3):520-7. doi: 10.1097/CCM.0000000000000029. PubMed 24201175 ↗
  • 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. PubMed 9972527 ↗
  • Barletta JF, Mangram AJ, Byrne M, Hollingworth AK, Sucher JF, Ali-Osman FR, Shirah GR, Dzandu JK. 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? J Trauma Acute Care Surg. 2016 Dec;81(6):1115-1121. doi: 10.1097/TA.0000000000001211. PubMed 27533906 ↗
  • Baptista JP, Udy AA, Sousa E, Pimentel J, Wang L, Roberts JA, Lipman J. A comparison of estimates of glomerular filtration in critically ill patients with augmented renal clearance. Crit Care. 2011 Jun 8;15(3):R139. doi: 10.1186/cc10262. PubMed 21651804 ↗
  • Baptista JP, Sousa E, Martins PJ, Pimentel JM. Augmented renal clearance in septic patients and implications for vancomycin optimisation. Int J Antimicrob Agents. 2012 May;39(5):420-3. doi: 10.1016/j.ijantimicag.2011.12.011. Epub 2012 Mar 3. PubMed 22386742 ↗
  • 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 Dec;38(6):462-7. doi: 10.1111/jcpt.12088. Epub 2013 Aug 8. PubMed 23924288 ↗
  • Lonsdale DO, Udy AA, Roberts JA, Lipman J. Antibacterial therapeutic drug monitoring in cerebrospinal fluid: difficulty in achieving adequate drug concentrations. J Neurosurg. 2013 Feb;118(2):297-301. doi: 10.3171/2012.10.JNS12883. Epub 2012 Nov 2. PubMed 23121433 ↗
  • Carlier M, Carrette S, Roberts JA, Stove V, Verstraete A, Hoste E, Depuydt P, Decruyenaere J, Lipman J, Wallis SC, De Waele JJ. 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 May 3;17(3):R84. doi: 10.1186/cc12705. PubMed 23642005 ↗
  • Roberts JA, Paul SK, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, Kaukonen KM, Koulenti D, Martin C, Montravers P, Rello J, Rhodes A, Starr T, Wallis SC, Lipman J; DALI Study. DALI: defining antibiotic levels in intensive care unit patients: are current beta-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis. 2014 Apr;58(8):1072-83. doi: 10.1093/cid/ciu027. Epub 2014 Jan 14. PubMed 24429437 ↗
  • Carrie C, Bentejac M, Cottenceau V, Masson F, Petit L, Cochard JF, Sztark F. 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 Feb;37(1):35-41. doi: 10.1016/j.accpm.2017.06.006. Epub 2017 Jul 26. PubMed 28756331 ↗
  • Lautrette A, Phan TN, Ouchchane L, Aithssain A, Tixier V, Heng AE, Souweine B. High creatinine clearance in critically ill patients with community-acquired acute infectious meningitis. BMC Nephrol. 2012 Sep 27;13:124. doi: 10.1186/1471-2369-13-124. PubMed 23013403 ↗
  • 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 Jun;47(6):800-808. doi: 10.1097/CCM.0000000000003716. PubMed 30870191 ↗
  • 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. PubMed 31832200 ↗
  • 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. PubMed 26942732 ↗
  • 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. PubMed 21048095 ↗
  • Cook AM, Hatton-Kolpek J. Augmented Renal Clearance. Pharmacotherapy. 2019 Mar;39(3):346-354. doi: 10.1002/phar.2231. Epub 2019 Mar 11. PubMed 30723936 ↗
  • Cook AM, Arora S, Davis J, Pittman T. Augmented renal clearance of vancomycin and levetiracetam in a traumatic brain injury patient. Neurocrit Care. 2013 Oct;19(2):210-4. doi: 10.1007/s12028-013-9837-y. PubMed 23907742 ↗
  • 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. PubMed 25761425 ↗
  • 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. PubMed 28926966 ↗
  • 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 Nov;35(11):1063-75. doi: 10.1002/phar.1653. PubMed 26598098 ↗
  • 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. PubMed 21554215 ↗
  • Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2010;49(1):1-16. doi: 10.2165/11318140-000000000-00000. PubMed 20000886 ↗
  • 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. PubMed 18579024 ↗
  • 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. PubMed 24277723 ↗
  • Mahmoud SH, Buxton J. Seizures and Choice of Antiepileptic Drugs Following Subarachnoid Hemorrhage: A Review. Can J Neurol Sci. 2017 Nov;44(6):643-653. doi: 10.1017/cjn.2017.206. PubMed 29391074 ↗
  • 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/ PubMed 21735578 ↗
  • 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 May-Jun;23(5):861-8. doi: 10.1016/j.jstrokecerebrovasdis.2013.07.017. Epub 2013 Aug 15. PubMed 23954598 ↗
  • 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. PubMed 25564314 ↗

Individual participant data

Plan to share: No — IPD will not be shared in accordance with maintaining patient confidentiality.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Oct 2021 (actual). Primary completion is estimated for Sep 2026, 59 months after the start.

Of 228 non-industry observational studies under Brain Injuries, Traumatic, half reached primary completion within 50 months of starting (the median), counting those still running; a quarter within 23 and three quarters within 95. This study's planned 59 months is above that.

Counting every sponsor, half of 250 studies reached it within 49 months; a quarter within 23 and three quarters within 95.

How these figures are worked out, and which studies are left out of them.

Registered
Feb 4, 2026
First posted
Feb 13, 2026
StartActual
Oct 1, 2021
Primary completionEst.
Sep 30, 2026
CompletionEst.
Sep 30, 2026
Last update
Feb 18, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 18, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07410624
Collaborators
University of Kentucky, Ohio State University
Responsible party
Sponsor
First posted
Feb 13, 2026
Start date
Oct 1, 2021
Primary completion
Sep 30, 2026 (estimated)
Completion
Sep 30, 2026 (estimated)
Last update
Feb 18, 2026

Study contacts

Sherif H Mahmoud, BSc (Pharm), MSc, PhD, FNCS
Contact
smahmoud@ualberta.ca
780.492.5364
Sherif H Mahmoud, BSc (Pharm), MSc, PhD, FNCS
principal investigator · University of Alberta

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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