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

NCT02549716 | Terminated Phase 4 Results DMC

• 1 other identifier: IRBSTUDY00002767
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Subarachnoid Hemorrhage; Stroke

Keywords

Acetaminophen; interleukin-6; interleukin-1; thromboxane A2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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.

Study Arms (2)

IV acetaminophen + oral placebo

EXPERIMENTAL

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.

Drug: IV acetaminophen; Drug: Oral placebo

Oral acetaminophen + IV placebo

EXPERIMENTAL

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.

Drug: Oral acetaminophen; Drug: IV placebo

Interventions

IV acetaminophen 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.

Also known as: Ofirmev, IV paracetamol

IV acetaminophen + oral placebo

Oral acetaminophen 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.

Also known as: Tylenol, paracetamol

Oral acetaminophen + IV placebo

Oral placebo DRUG

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

Also known as: placebo

IV acetaminophen + oral placebo

IV placebo 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).

Also known as: placebo, saline solution

Oral acetaminophen + IV placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Stroke

Interventions

Acetaminophen; Saline Solution

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Study was terminated early

Results Point of Contact

• Title: Sprague W. Hazard III, M.D.
• Organization: Milton S. Hershey Medical Center

shazard@pennstatehealth.psu.edu

717-531-0003

Study Officials

• Sprague W Hazard, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anesthesiology

Study Record Dates

• First Submitted: July 1, 2015
• First Posted: September 15, 2015
• Study Start: January 5, 2017
• Primary Completion: June 8, 2018
• Study Completion: June 8, 2018
• Last Updated: April 10, 2019
• Results First Posted: April 10, 2019

Record last verified: 2019-03

Locations

US (1)