Acetaminophen in Combination With N-Acetylcysteine (NAC) Versus Placebo in Treating Fever

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy of the an N-acetyl-p-aminophenol (APAP, also known as acetaminophen) and N-acetylcysteine (NAC) combination versus an APAP-placebo combination as an anti-pyretic agent.

Detailed Description
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N-acetyl-p-aminophenol (APAP), or more commonly known as acetaminophen in the United States, accounts for more overdose and overdose deaths in the United States and United Kingdom than any other pharmaceutical agent. If N-acetylcysteine (NAC) is given within 8 to 10 hours of APAP ingestion, it has been shown to prevent serious liver failure and death in the setting of overdoses. Therefore, it may be beneficial to administer APAP in combination with NAC routinely to reduce rates of liver failure and death. Because NAC's main role is to reduce the accumulation of APAP's toxic metabolites, the concomitant administration of NAC should have no impact on the efficacy of APAP as an antipyretic and analgesic. Thus, we propose a single-center, non-inferiority randomized control study comparing the efficacy of the APAP-NAC combination as compared to APAP-placebo as an anti-pyretic agent.

Official Title
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Acetaminophen in Combination With N-Acetylcysteine (NAC) vs. Placebo in the Treatment of Fever: A Double-Blind, Randomized Control Study

Conditions
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Liver Failure, Liver Failure, Acute, Drug Induced Liver Injury, Prevention & Control, Fever

Intervention / Treatment
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* Drug: APAP and NAC combination
* Drug: APAP and Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adults aged 18 to 75 years old admitted to an inpatient unit at Columbia-Presbyterian Medical Center fever defined as an oral temperature of 38.5°C Exclusion Criteria: if oral temperature cannot be obtained abnormal aminotransferase levels prior adverse reaction to acetaminophen or N-acetylcysteine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APAP and NAC combination<br>N-acetyl-p-aminophenol and placebo (APAP-NAC) combination pill | Drug: APAP and NAC combination<br>* APAP 650mg and NAC 600mg combination oral tablet administered once<br>* Other names: NAC: n-acetylcysteine; Mucomyst;|
| Placebo Comparator: APAP and Placebo combination<br>N-acetyl-p-aminophenol and placebo (APAP-placebo) combination pill | Drug: APAP and Placebo<br>* APAP 650mg and Placebo combination oral tablet administered once<br>* Other names: APAP: n-acetyl-p-aminophenol; acetaminophen; Tylenol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in temperature reduction between participants who are administered combination N-acetyl-p-aminophenol and N-Acetylcysteine (APAP-NAC) versus combination APAP-placebo |  | 6 hours after study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in liver function tests after study drug administration between participants who are administered combination N-acetyl-p-aminophenol and N-Acetylcysteine (APAP-NAC) versus combination APAP-placebo | Change in serum total protein (TP), albumin (Alb), total bilirubin (TB), direct bilirubin (DB), amino alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatate (AP) levels before and after the study drug administration. | Within 24 hours of study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acetaminophen, Acetylcysteine, Antidotes