Clinical, Pharmacological and Molecular Effects of IV and Oral Acetaminophen in Adults With aSAH

Stroke Clinical Trial

— aSAH  

Official title:

Clinical, Pharmacological and Molecular Effects of Intravenous and Oral Acetaminophen in Adults With Aneurysmal Sub-Arachnoid Hemorrhage

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02549716
• Other study ID #: IRBSTUDY00002767
• Status: Terminated
• Phase: Phase 4
• Start date: January 5, 2017
• Est. completion date: June 8, 2018

Study information

• Verified date: March 2019
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: June 8, 2018
• Est. primary completion date: June 8, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Hemorrhage
• Stroke
• Subarachnoid Hemorrhage

Intervention

Drug:
• IV acetaminophen
Patients in this group will receive IV acetaminophen and an oral placebo every 6 hours for a 14 day period. Blood and CSF samples will be collected from patients throughout the 14 day period.
• Oral acetaminophen
Patients in this group will receive oral acetaminophen and an IV saline solution placebo every 6 hours for a 14 day period. Blood and CSF samples will be collected from patients throughout the 14 day period.
• Oral placebo
Patients who receive IV acetaminophen will also receive an oral placebo with their IV treatments (every 6 hours for a 14 day period).
• IV placebo
Patients who receive oral acetaminophen will also receive a saline solution placebo at the same time that they receive the oral acetaminophen treatment (every 6 hours for 14 days).

Locations

Country	Name	City	State
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bioavailability of Acetaminophen in Cerebral Spinal Fluid (CSF) and Blood	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.	Time = 0, 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes after first drug administration
Secondary	Concentrations of Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Thromboxane A-2 (TXA-2) in Cerebral Spinal Fluid (CSF) and Blood	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. These samples will be examined to determine concentrations of Interleukin-1 (IL-1), Interleukin-6 (IL-6), and thromboxane A-2 (TXA-2) in both the Cerebral Spinal Fluid (CSF) and blood. This will enable the team to determine if route of entry of acetaminophen plays a significant role in the level of inflammatory markers in critically ill patients.	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).
Secondary	Number of Febrile Periods	Patients in both IV and PO groups will have their temperatures taken at the times listed. This will help determine if route of entry of acetaminophen plays a significant role in the 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).
Secondary	Incidence of Vasospasm	The investigators will measure the incidence of vasospasm in patients with subarachnoid hemorrhage (SAH) who receive 1g Q6 of IV acetaminophen starting on post-bleed day 0 and continuing for 14 consecutive days (typical vasospasm window). Clinical vasospasm will be defined as the presence of new focal neurological deficits (motor or speech deficits) that developed after subarachnoid hemorrhage (SAH), a decrease in the Glasgow Coma Score (GCS) of 2 or more points for >6hrs, a new cerebral infarction unrelated to post-treatment (coiling or clipping) complications, re-bleed, progressive hydrocephalus, electrolyte or metabolic disturbance, or infection. The incidence of clinical vasospasm will be identified in the patients Electronic Medical Record (EMR) after the 14 day period.	Days 0-14 following diagnosis with subarachnoid hemorrhage.