Clinical, Pharmacological and Molecular Effects of Intravenous and Oral Acetaminophen in Adults With Aneurysmal Sub-Arachnoid Hemorrhage
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Bioavailability of Acetaminophen in Cerebral Spinal Fluid (CSF) and Blood
研究概览
简要总结
This study compares the bioavailability of IV and PO acetaminophen in both blood and the cerebrospinal fluid (CSF) of patients following subarachnoid hemorrhage. The study will also compare the temperature and levels of inflammatory cytokines in both blood and CSF of patients treated with IV and PO acetaminophen.
详细描述
In individuals diagnosed with subarachnoid hemorrhage (SAH), fevers have been shown to have detrimental micro and macroscopic effects on the brain that can ultimately cause secondary brain injury. The anti-pyretic effects of oral acetaminophen have been studied in critically ill patients but no study has been able to compare these effects to the IV form of acetaminophen also known as OFIRMEV. The investigators wish to explore the notion that IV acetaminophen will be more effective than enteral acetaminophen in reducing the incidence of non-infectious fevers in critically ill patients. In addition, the investigators propose to study the levels of inflammatory cytokines after administration of IV or enteral acetaminophen, as well as, determine the incidence of vasospasm in SAH patients treated with IV acetaminophen. Currently, external ventricular drain (EVD) placement is the "standard of care" in patients who present with SAH and altered mental status/coma. The presence of an EVD allows for continuous sampling and removal of cerebral spinal fluid (CSF) as necessary to alleviate dangerous elevations in intracranial pressure. This clinical scenario allows for a unique, continuous outlet to access the CSF, without placing patients at risk, and without further invasive procedures (i.e. repeated spinal taps). These samples of CSF can be assayed for levels of acetaminophen, as well as inflammatory markers of fever which include interleukin-1 (IL-1), interleukin-6 (IL-6), and thromboxane-2 (TXA-2), in patients selected to be given enteral or IV acetaminophen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of subarachnoid hemorrhage (must be confirmed by CT, CT angiography, lumbar puncture, or MRI).
- •Fisher Grade between 1-3 (subarachnoid blood without signs of intraventricular hemorrhage or parenchymal extension).
- •Placement of an external ventricular drain.
- •Adults aged 18-100 years.
排除标准
- •Anyone under the age of 18 or over the age of
- •Adult patients with subarachnoid hemorrhage with interventricular hemorrhage or parenchymal extension (Fisher Grade 4).
- •Contraindication to acetaminophen such as a known hypersensitivity, severe hepatic impairment, or severe active liver disease.
- •Severe renal impairment (creatinine clearance ≤ 30 mL/min).
研究组 & 干预措施
IV acetaminophen + oral placebo
Patients in this group will receive IV acetaminophen and an oral placebo. The IV formulation will be given using the FDA approved OFIRMEV which comes in a single glass bottle at a concentration of 1000mg/100ml (10mg/ml) containing a total of 1 gram of acetaminophen.
干预措施: IV acetaminophen (Drug)
IV acetaminophen + oral placebo
Patients in this group will receive IV acetaminophen and an oral placebo. The IV formulation will be given using the FDA approved OFIRMEV which comes in a single glass bottle at a concentration of 1000mg/100ml (10mg/ml) containing a total of 1 gram of acetaminophen.
干预措施: Oral placebo (Drug)
Oral acetaminophen + IV placebo
Patients in this group will receive oral acetaminophen and a saline solution placebo through their IV. The enteral formulation will be in the standard tablet form of 500mg per pill. Patients will receive two pills, or 1 gram of acetaminophen.
干预措施: Oral acetaminophen (Drug)
Oral acetaminophen + IV placebo
Patients in this group will receive oral acetaminophen and a saline solution placebo through their IV. The enteral formulation will be in the standard tablet form of 500mg per pill. Patients will receive two pills, or 1 gram of acetaminophen.
干预措施: IV placebo (Drug)
结局指标
主要结局
Bioavailability of Acetaminophen in Cerebral Spinal Fluid (CSF) and Blood
时间窗: Time = 0, 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes after first drug administration
Patients in both IV and PO groups will have samples taken from their Cerebral Spinal Fluid (CSF) and blood at the above times after acetaminophen is administered for the first time. They will then have additional samples taken every 24 hours following the time of first drug administration for 14 days. Patients will also have a sample collected every 35 hours (1 hour before the 6th loading dose) to determine the steady state level of acetaminophen.
次要结局
- Concentrations of Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Thromboxane A-2 (TXA-2) in Cerebral Spinal Fluid (CSF) and Blood(Time = 0, 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes after first drug administration. Additionally, every 24 hours after time t=0 for 14 days (14 additional samples from both blood and CSF).)
- Number of Febrile Periods(Time = 0, 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes after first drug administration. Additionally, every 24 hours after time t=0 for 14 days (14 additional samples from both blood and CSF).)
- Incidence of Vasospasm(Days 0-14 following diagnosis with subarachnoid hemorrhage.)
研究者
Sprague W Hazard III
Assistant Professor of Anesthesiology
Milton S. Hershey Medical Center