Clinical trial NCT02549716: Clinical, Pharmacological and Molecular Effects of IV and Oral Acetaminophen in Adults With aSAH
Official title: Clinical, Pharmacological and Molecular Effects of Intravenous and Oral Acetaminophen in Adults With Aneurysmal Sub-Arachnoid Hemorrhage
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Subarachnoid Hemorrhage
Stroke
Keywords: Acetaminophen
interleukin-6
interleukin-1
thromboxane A2
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2015-09-15
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Anyone under the age of 18 or over the age of 100.
* 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).

Primary outcomes:
measure: Bioavailability of Acetaminophen in Cerebral Spinal Fluid (CSF) and Blood
timeFrame: Time = 0, 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes after first drug administration
Secondary outcomes:
measure: Concentrations of Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Thromboxane A-2 (TXA-2) in Cerebral Spinal Fluid (CSF) and Blood
timeFrame: 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).
measure: Number of Febrile Periods
timeFrame: 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).
measure: Incidence of Vasospasm
timeFrame: Days 0-14 following diagnosis with subarachnoid hemorrhage.
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
Study officials:
affiliation: "Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
name: Sprague W Hazard, MD
role: PRINCIPAL_INVESTIGATOR
References: