Evaluation of the Efficacy of Fomepizole in the Treatment of Acetaminophen Overdose

• Status: Not yet recruiting
• Trial end date: 2025-11-30
• Target enrollment: 0
• Participant gender: All

Summary

This study is a randomized, placebo-controlled double-blinded clinical trial of patients presenting with acetaminophen poisoning who are at increased risk of developing liver injury. With this trial the investigators are hoping to show the superiority of acetylcysteine (NAC) + fomepizole (4-MP) compared to treatment with acetylcysteine alone. The primary objective of this trial is to determine the effect of fomepizole on the severity of acute liver injury in patients with acetaminophen poisoning.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Richard Dart, MD, PhD
• Collaborator: Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division
• Treatments: Acetylcysteine; Fomepizole; N-monoacetylcystine

Criteria

Inclusion Criteria:

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with mandatory study procedures and availability for the duration of the study

3. Adults ages 18 years or older

4. Evidence of acetaminophen ingestion (serum acetaminophen greater or equal to 10 mg/L) after correction for bilirubin, when applicable

5. Baseline AT Multiplication Product at screening ([APAP] multiplied by the serum AST or ALT in IU/L, whichever is higher) of 1500 or higher

6. If acute ingestion, more than 5 hours elapsed from the time of ingestion and the time screening tests were performed

7. Patient planned to be admitted to hospital for treatment and/or observation or treatment in Emergency Department

Exclusion Criteria:

1. Serum ALT greater than 1000 IU/L at time of screening

2. Another overdose episode with acetaminophen within the preceding 14 days

3. Serum alcohol concentration over 100 mg/dL (serum or breathalyzer allowed)

4. History of preexisting liver disease with last ALT > 100 IU/L before current illness. If ALT is ≤ 100 then that value should be at least 50% higher than the highest in the preceding 12 months.

5. History of liver cirrhosis diagnosis or current clinical evidence of liver cirrhosis regardless of serum ALT activity

6. Known allergic reaction to acetylcysteine or fomepizole

7. Pregnancy or lactation

8. 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.

9. Concomitant ingestion of high dosage iron preparations (e.g. prenatal iron sulfate capsules)

10. 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 be 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

11. Treatment with another investigational drug within the preceding 30 days.

12. Previous participation in this study