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Trial record 7 of 1888 for:    ACETAMINOPHEN

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

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ClinicalTrials.gov Identifier: NCT02549716
Recruitment Status : Terminated (Funding was stopped)
First Posted : September 15, 2015
Results First Posted : April 10, 2019
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Sprague W Hazard III, Milton S. Hershey Medical Center

Tracking Information
First Submitted Date  ICMJE July 1, 2015
First Posted Date  ICMJE September 15, 2015
Results First Submitted Date  ICMJE February 28, 2019
Results First Posted Date  ICMJE April 10, 2019
Last Update Posted Date April 10, 2019
Actual Study Start Date  ICMJE January 5, 2017
Actual Primary Completion Date June 8, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2019)
Bioavailability of Acetaminophen in Cerebral Spinal Fluid (CSF) and Blood [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 11, 2015)
Bioavailability of Acetaminophen in CSF and blood [ Time Frame: 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 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.
Change History Complete list of historical versions of study NCT02549716 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2019)
  • Concentrations of Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Thromboxane A-2 (TXA-2) in Cerebral Spinal Fluid (CSF) and Blood [ Time Frame: 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). ]
    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.
  • Number of Febrile Periods [ Time Frame: 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). ]
    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.
  • Incidence of Vasospasm [ Time Frame: Days 0-14 following diagnosis with subarachnoid hemorrhage. ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2015)
  • Concentrations of IL-1, IL-6, and TXA-2 in CSF and blood [ Time Frame: 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). ]
    Patients in both IV and PO groups will have samples taken from their 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 IL-1, IL-6, and TXA-2 in both the 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.
  • Number of Febrile Periods [ Time Frame: 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). ]
    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.
  • Incidence of Vasospasm [ Time Frame: Days 0-14 following diagnosis with subarachnoid hemorrhage. ]
    The investigators will measure the incidence of vasospasm in patients with 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 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 EMR after the 14 day period.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical, Pharmacological and Molecular Effects of IV and Oral Acetaminophen in Adults With aSAH
Official Title  ICMJE Clinical, Pharmacological and Molecular Effects of Intravenous and Oral Acetaminophen in Adults With Aneurysmal Sub-Arachnoid Hemorrhage
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Subarachnoid Hemorrhage
  • Stroke
Intervention  ICMJE
  • 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.
    Other Names:
    • Ofirmev
    • IV paracetamol
  • 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.
    Other Names:
    • Tylenol
    • paracetamol
  • 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).
    Other Name: placebo
  • 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).
    Other Name: placebo, saline solution
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Drug: IV acetaminophen
    • Drug: Oral placebo
  • Experimental: 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.
    Interventions:
    • Drug: Oral acetaminophen
    • Drug: IV placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 20, 2019)
3
Original Estimated Enrollment  ICMJE
 (submitted: September 11, 2015)
50
Actual Study Completion Date  ICMJE June 8, 2018
Actual Primary Completion Date June 8, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02549716
Other Study ID Numbers  ICMJE IRBSTUDY00002767
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sprague W Hazard III, Milton S. Hershey Medical Center
Study Sponsor  ICMJE Milton S. Hershey Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sprague W Hazard, MD "Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
PRS Account Milton S. Hershey Medical Center
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP