Augmented Renal Clearance in Neurocritical Care Population: A Prospective Multicenter Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 512
- 试验地点
- 3
- 主要终点
- CrCl Measurements
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •Incarceration
- •Anticipated ICU length of stay is < 72 hours (insufficient time for monitoring)
研究组 & 干预措施
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).
结局指标
主要结局
CrCl Measurements
时间窗: 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
Drug Concentration Determination
时间窗: 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.
次要结局
未报告次要终点