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

NCT ID: NCT02549716

Last Updated: 2019-04-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-05
• Study Completion Date: 2018-06-08

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.

Conditions

Subarachnoid Hemorrhage; Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

IV acetaminophen

Intervention Type: DRUG

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 placebo

Intervention Type: DRUG

Patients who receive IV acetaminophen will also receive an oral placebo with their IV treatments (every 6 hours for a 14 day period).

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.

Group Type: EXPERIMENTAL

Oral acetaminophen

Intervention Type: DRUG

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.

IV placebo

Intervention Type: DRUG

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).

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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).

Intervention Type: DRUG

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).

Intervention Type: DRUG

Other Intervention Names

Ofirmev; IV paracetamol; Tylenol; paracetamol; placebo; placebo, saline solution

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Sprague W Hazard III

Assistant Professor of Anesthesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sprague W Hazard, MD

Role: PRINCIPAL_INVESTIGATOR

"Penn State College of Medicine, Penn State Milton S. Hershey Medical Center

Locations

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRBSTUDY00002767

Identifier Type: -

Identifier Source: org_study_id