TBI (Traumatic Brain Injury)Neuro-ARCNCT07410624
Augmented Renal Clearance in Neurocritical Care
An observational study of TBI (Traumatic Brain Injury) and Status Epilepticus, run by University of Alberta at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- TBI (Traumatic Brain Injury), Status Epilepticus, Bacterial Meningitis
- How many people
- 512 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 1 Oct 2021to 30 Sep 2026
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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)
Who cannot join
- Incarceration
- Anticipated ICU length of stay is < 72 hours (insufficient time for monitoring)
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 2 countries
United States2 sites, 2 recruiting
- Recruiting
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Casey May, PharmD, BCCCP, FNCS, (614) 814-6519, may.645@osu.edu
- Recruiting
UK HealthCare
Lexington, Kentucky, 40536
Aaron Cook, PharmD, BCCCP, FKSHP, FCCP, 859-257-8444, amcook0@email.uky.edu
Canada1 site, 1 recruiting
- Recruiting
University of Alberta Hospital
Edmonton, Alberta, T6G 2X8
Sherif H Mahmoud, BSc (Pharm), MSc, PhD, FNCS, 780-492-5364, smahmoud@ualberta.ca
Sherif Mahmoud, BSc (Pharm), MSc, PhD, FNCS
About this study
Official title: Augmented Renal Clearance in Neurocritical Care Population: A Prospective Multicenter Study
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:
- To characterize the phenomenon of ARC in neurocritical care population (prevalence, duration and impact on hospital outcomes).
- To measure the impact of ARC on the disposition of commonly used renally eliminated medications in neurocritical care.
- 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.
- Conditions
- TBI (Traumatic Brain Injury), Status Epilepticus, Bacterial Meningitis, Augmented Renal Clearance (ARC), Subarachnoid Hemorrhage, Aneurysmal, Ischemic Stroke
- 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
- Medical subject headings
- Brain Injuries, Traumatic, Status Epilepticus, Meningitis, Bacterial, Subarachnoid Hemorrhage, Ischemic Stroke, Cerebral Hemorrhage, Seizures, Trauma, Nervous System
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2026
- Study start1 Oct 2021
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for TBI (Traumatic Brain Injury)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 512 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- University of Kentucky, Ohio State University
- Responsible party
- Sponsor
- Investigators
- Sherif H Mahmoud, BSc (Pharm), MSc, PhD, FNCS, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07410624
- Sponsor's protocol ID
- Pro00112754
- Acronym
- Neuro-ARC
- Status last verified
- Feb 2026
- First submitted
- 4 Feb 2026
- Last updated
- 18 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared in accordance with maintaining patient confidentiality.
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 24201175Markantonis 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 9972527Barletta 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 27533906Baptista 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 21651804Baptista 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 22386742Minkute 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 23924288Lonsdale 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 23121433Carlier 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 23642005Roberts 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 24429437Carrie 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 28756331Lautrette 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 23013403Morbitzer 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 30870191Morbitzer 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 31832200Morbitzer 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 26942732Udy 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