Evaluation of the Efficacy of Fomepizole in the Treatment of Acetaminophen Overdose
Acetaminophen, Drug Overdose, Acetaminophen Overdose
About this trial
This is an interventional treatment trial for Acetaminophen
Eligibility Criteria
Inclusion Criteria:
- Provision of signed and dated informed consent form
- Stated willingness to comply with mandatory study procedures and availability for the duration of the study
- Adults ages 18 years or older
- Evidence of acetaminophen ingestion (serum acetaminophen greater or equal to 10 mg/L) after correction for bilirubin, when applicable
- Baseline AT Multiplication Product at screening ([APAP] multiplied by the serum AST or ALT in IU/L, whichever is higher) of 1500 or higher
- If acute ingestion, more than 5 hours elapsed from the reliable time of ingestion and the time screening tests were performed. Acute ingestion is defined as less than 8 hours from the time of first ingestion of acetaminophen containing product to last ingestion of acetaminophen containing product.
- Patient planned to be admitted to hospital for treatment and/or observation or treatment in Emergency Department
Exclusion Criteria:
- Serum ALT greater than 3300 IU/L or serum AST greater than 5400 IU/L at time of screening
- Another overdose episode with acetaminophen within the preceding 14 days
- Serum alcohol concentration over 100 mg/dL (serum or breathalyzer allowed)
- Baseline ALT (defined as average of ALTs reported in preceding 12 months) above the ALT reference range for the hospital laboratory unless screening ALT is at least twice the patient's baseline value.
- History of liver cirrhosis diagnosis or current clinical evidence of liver cirrhosis regardless of serum ALT activity
- Known allergic reaction to acetylcysteine or fomepizole
- Pregnancy or lactation
- Co-ingestion of other known activators or inhibitors of CYP2E1 (acetone, cimetidine, nicotine, isoniazid, pyridine, pyrazole, disulfiram). History of cigarette smoking, use of nicotine patches are allowed.
- Concomitant ingestion of high dosage iron preparations (e.g. prenatal iron sulfate capsules)
In the site investigator's judgment, the patient has a condition that would interfere with evaluation of the efficacy of fomepizole. These conditions include, but are not limited to the following conditions:
- Seizure in the previous 24 hours. History of seizure disorder under chronic treatment is allowed
- Cardiac arrest in the preceding 14 days
- Cardiac dysrhythmia that comprises cardiovascular function at screening
- History of liver transplant
- Hypotension or cardiovascular shock in preceding 72 hours
- Treatment with another investigational drug within the preceding 30 days.
- Previous participation in this study
Sites / Locations
- Denver Health and Hospital AuthorityRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
N-acetylcysteine (NAC) only (Control)
N-acetylcysteine (NAC) and Fomepizole (4-MP) (Study)
Patients randomized to Control group will receive placebo (D5W) in addition to N-acetylcysteine. Study participants will receive study drug (fomepizole or placebo) throughout the study.
Patients randomized to Study group will receive fomepizole (diluted in D5W) in addition to N-acetylcysteine. Study participants will receive study drug (fomepizole or placebo) throughout the study. If randomized to Study group, the participant will receive fomepizole in a fixed dose relative to acetylcysteine. The fixed ratio is acetylcysteine 10 : 1 fomepizole. In the first 20-21 hours (2 vs. 3-bag regimen), a total of 30 mg/kg fomepizole is delivered.