Clinical trial NCT01137591: Acetaminophen in Combination With N-Acetylcysteine (NAC) Versus Placebo in Treating Fever
Official title: Acetaminophen in Combination With N-Acetylcysteine (NAC) vs. Placebo in the Treatment of Fever: A Double-Blind, Randomized Control Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Liver Failure
Liver Failure, Acute
Drug Induced Liver Injury
Prevention & Control
Fever
Keywords: Acetaminophen
Acetylcysteine
Antidotes
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2010-06-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Difference in temperature reduction between participants who are administered combination N-acetyl-p-aminophenol and N-Acetylcysteine (APAP-NAC) versus combination APAP-placebo
timeFrame: 6 hours after study drug administration
Secondary outcomes:
measure: 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
timeFrame: Within 24 hours of study drug administration
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Matthew Chang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bronstein AC, Spyker DA, Cantilena LR Jr, Green J, Rumack BH, Heard SE. 2006 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS). Clin Toxicol (Phila). 2007 Dec;45(8):815-917. doi: 10.1080/15563650701754763.
citation: Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med. 1988 Dec 15;319(24):1557-62. doi: 10.1056/NEJM198812153192401.
citation: Vale JA, Proudfoot AT. Paracetamol (acetaminophen) poisoning. Lancet. 1995 Aug 26;346(8974):547-52. doi: 10.1016/s0140-6736(95)91385-8. No abstract available.