Augmented Renal Clearance in Neurocritical Care (Neuro-ARC)

February 15, 2026 updated by: University of Alberta

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.

Study Overview

Status

Recruiting

Conditions

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.

Study Type

Observational

Enrollment (Estimated)

512

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Sherif H Mahmoud, BSc (Pharm), MSc, PhD, FNCS
  • Phone Number: 780.492.5364
  • Email: smahmoud@ualberta.ca

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2X8
        • Recruiting
        • University of Alberta Hospital
        • Contact:
          • Sherif H Mahmoud, BSc (Pharm), MSc, PhD, FNCS
          • Phone Number: 780-492-5364
          • Email: smahmoud@ualberta.ca
        • Principal Investigator:
          • Sherif Mahmoud, BSc (Pharm), MSc, PhD, FNCS
  • United States
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • UK HealthCare
        • Contact:
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University Wexner Medical Center
        • Contact:
          • Casey May, PharmD, BCCCP, FNCS
          • Phone Number: (614) 814-6519
          • Email: may.645@osu.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

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.

Description

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 informed consent
  5. Foley catheter in place at time of consent (to facilitate urine collection)

Exclusion Criteria:

  1. Incarceration
  2. Anticipated ICU length of stay is < 72 hours (insufficient time for monitoring)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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 the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CrCl Measurements
Time Frame: During hospital admission from enrolment for 10 days or until discharge from ICU, whichever comes first.
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
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alberta

Collaborators

Ohio State University
University of Kentucky

Investigators

  • Principal Investigator: Sherif H Mahmoud, BSc (Pharm), MSc, PhD, FNCS, University of Alberta

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2021

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2026

Study Registration Dates

First Submitted

February 4, 2026

First Submitted That Met QC Criteria

February 7, 2026

First Posted (Actual)

February 13, 2026

Study Record Updates

Last Update Posted (Actual)

February 18, 2026

Last Update Submitted That Met QC Criteria

February 15, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00112754

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD will not be shared in accordance with maintaining patient confidentiality.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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