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

Fever Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01137591
• Other study ID #: AAAD4090
• Status: Withdrawn
• Phase: N/A
• First received: June 3, 2010
• Last updated: March 3, 2015
• Start date: April 2009

Study information

• Verified date: March 2015
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Drug Induced Liver Injury
• Drug-Induced Liver Injury
• Fever
• Liver Failure
• Liver Failure, Acute
• Prevention & Control

Intervention

Drug:
• APAP and NAC combination
APAP 650mg and NAC 600mg combination oral tablet administered once
• APAP and Placebo
APAP 650mg and Placebo combination oral tablet administered once

Locations

Country	Name	City	State
United States	Columbia University Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View Citation

Vale JA, Proudfoot AT. Paracetamol (acetaminophen) poisoning. Lancet. 1995 Aug 26;346(8974):547-52. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes

External Links

•   Acetaminophen overdose information from the NIH