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Trial record 2 of 1933 for:    ACETAMINOPHEN

APAP-CYS Protein Adduct Concentrations in Patients With Liver-Directed Therapy Intended to Treat Hepatic Tumors

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ClinicalTrials.gov Identifier: NCT02911961
Recruitment Status : Recruiting
First Posted : September 23, 2016
Last Update Posted : January 29, 2020
Sponsor:
Collaborators:
Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division
University of Colorado, Denver
Rocky Mountain Poison and Drug Center
Information provided by (Responsible Party):
Kennon Heard, Denver Health and Hospital Authority

Tracking Information
First Submitted Date  ICMJE August 17, 2016
First Posted Date  ICMJE September 23, 2016
Last Update Posted Date January 29, 2020
Estimated Study Start Date  ICMJE February 1, 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 30, 2018)
APAP-CYS Concentrations Over Time - Acetaminophen Group [ Time Frame: 14 days ]
To describe the course of APAP-CYS concentrations following hepatic embolization in subjects who receive 4 grams/day of acetaminophen for three days prior to the procedure
Original Primary Outcome Measures  ICMJE
 (submitted: September 20, 2016)
APAP-CYS Concentrations Over Time - Acetaminophen Group [ Time Frame: 2 years ]
To describe the course of APAP-CYS concentrations following hepatic embolization in subjects who receive 4 grams/day of acetaminophen for three days prior to the procedure
Change History Complete list of historical versions of study NCT02911961 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2018)
  • APAP-CYS Concentrations Over Time - Non-Acetaminophen Group [ Time Frame: 2 years ]
    To determine if subjects who report no exposure to acetaminophen prior to the procedure have detectable APAP-CYS concentrations
  • Relationship between APAP-CYS and other biochemical markers of liver function [ Time Frame: 2 years ]
    To evaluate the relationship between APAP-CYS concentrations with aspartate aminotransferase (AST), alanine aminotransferase (ALT), and miRNA activity
Original Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2016)
  • APAP-CYS Concentrations Over Time - Non-Acetaminophen Group [ Time Frame: 2 years ]
    To determine if subjects who report no exposure to acetaminophen prior to the procedure have detectable APAP-CYS concentrations
  • Relationship between APAP-CYS and other biochemical markers of liver function [ Time Frame: 2 years ]
    To evaluate the relationship between APAP-CYS concentrations with aspartate aminotransferase (AST), alanine aminotransferase (ALT), and miRNA activity
  • Accuracy of Medication History Assessment Tool (MedHAT) [ Time Frame: 2 years ]
    To evaluate the Medication History Assessment Tool (MedHAT) in an oncology population (Exploratory objective)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE APAP-CYS Protein Adduct Concentrations in Patients With Liver-Directed Therapy Intended to Treat Hepatic Tumors
Official Title  ICMJE Serum Acetaminophen-Cysteine (APAP-CYS) Adduct Concentrations in Subjects Expected to Develop Aminotransferase Elevations With Liver-Directed Therapy Intended to Treat Hepatic Tumors
Brief Summary The objective of this study is to provide preliminary data to describe serum acetaminophen-cysteine protein adduct (APAP-CYS) concentrations following therapeutic doses of acetaminophen in the setting of non-acetaminophen induced liver injury. This study will utilize hepatic embolization as a model of hepatic injury.
Detailed Description Acetaminophen-cysteine protein adducts (APAP-CYS) are formed when acetaminophen is oxidized by CYP 2E-1. When hepatocytes die, these proteins are released into the serum and can be detected. APAP-CYS can therefore be an experimental biomarker of acetaminophen exposure. It is possible that massive necrosis of hepatocytes that contain APAP-CYS from therapeutic doses of acetaminophen can be misinterpreted as acetaminophen overdose as the cause of liver injury. This study aims to describe serum APAP-CYS concentrations in patients taking a therapeutic dose of acetaminophen who develop a liver injury from a cause other than acetaminophen. This study will seek to enroll subjects undergoing a hepatic embolization procedure to treat a secondary liver tumor. This procedure is a reproducible model of non-acetaminophen induced hepatic injury. A small number of subjects who are otherwise eligible to participate but are unwilling to take acetaminophen will be offered participation in the observational arm of the study. They will undergo the same assessments with the exception of acetaminophen dosing. Subjects willing to take acetaminophen will be asked to take extra strength acetaminophen (4g/day) for the 3 days prior to their embolization procedure. All subjects will be asked to keep a detailed medication diary for the three days prior and up to their embolization procedure. Blood samples for the measurement of APAP-CYS concentrations and markers of liver function will be collected prior to acetaminophen dosing, prior to the embolization procedure, and at several time points after the procedure.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Condition  ICMJE Acetaminophen Exposure
Intervention  ICMJE Drug: Acetaminophen
1 gram acetaminophen 4 times a day with at least 6 hour intervals between doses for the 3 days prior to the embolization procedure.
Other Name: Tylenol
Study Arms  ICMJE
  • Experimental: Acetaminophen
    Subjects will take extra strength acetaminophen (4g/day) for the three days prior to the embolization procedure.
    Intervention: Drug: Acetaminophen
  • No Intervention: Observational - No Acetaminophen
    Subjects will take no acetaminophen containing products prior to the embolization procedure.
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 20, 2016)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects of any gender or ethnic background who are between 21 and 80 years old
  • Subjects who are able to provide written, informed consent
  • Subjects with secondary liver cancer
  • Subjects undergoing portal vein or bland embolization for the treatment of secondary hepatic tumor
  • Subjects who are willing to have their blood drawn at least 12 times for study purposes
  • Subjects who agree to stay for ~18-21 hours after being discharged from the Department of Radiology for research purposes
  • Subjects who agree to refrain from using acetaminophen, other than the study drug, during the dosing phase through a minimum of 5 days post-procedure
  • Subjects who agree to consume less than 3 alcoholic drinks per day while taking study drug (acetaminophen group only)
  • Subjects who are willing to complete a study diary for 3 days prior to and the day of the procedure
  • Subjects who will be in the Denver metro area for the duration of the study

Exclusion Criteria:

  • Subjects with known cirrhosis
  • Subjects with a history of moderate to severe anemia at screening as defined by:

    1. Moderate: Hemoglobin 8-9.5 g/dL
    2. Severe: Hemoglobin <8 g/dL
  • Subjects with an ALT or AST greater than 200 IU/L at screening
  • Subjects with a total bilirubin greater than 1.5 mg/dL at screening
  • Subjects with an INR greater than 1.3 at screening
  • Subjects with a platelet count less than 125 10^9/L at screening
  • Subjects who are currently taking warfarin (acetaminophen group only)
  • Subjects with anorexia nervosa (self-reported; acetaminophen group only)
  • Subjects who weigh ≤50 kg at screening (acetaminophen group only)
  • Subjects who adhere to a fasting type diet (self-reported; acetaminophen group only)
  • Subjects with a known hypersensitivity or allergy to acetaminophen (acetaminophen group only)
  • Subjects who are currently taking isoniazid (acetaminophen group only)
  • Subjects who are currently taking disulfiram (acetaminophen group only)
  • Subjects who are pregnant or breastfeeding (female participants only)
  • Subjects who are currently enrolled in a clinical trial, have participated in a clinical trial within the 30 days prior to the procedure, or who plan to participate in a clinical trial during the 5 day post-procedure follow-up period
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Research Coordinator 303-389-1800 Clinical.Trials@rmpdc.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02911961
Other Study ID Numbers  ICMJE 16-0031
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kennon Heard, Denver Health and Hospital Authority
Study Sponsor  ICMJE Denver Health and Hospital Authority
Collaborators  ICMJE
  • Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division
  • University of Colorado, Denver
  • Rocky Mountain Poison and Drug Center
Investigators  ICMJE
Principal Investigator: Kennon Heard, MD, PhD University of Colorado, Denver
PRS Account Denver Health and Hospital Authority
Verification Date January 2020

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