Liver FailureNCT01137591
Acetaminophen in Combination With N-Acetylcysteine (NAC) Versus Placebo in Treating Fever
A study testing APAP and NAC combination in people with Liver Failure and Liver Failure, Acute, run by Columbia University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Failure, Liver Failure, Acute, Drug Induced Liver Injury
- What is being tested?
- APAP and NAC combination
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2009to not given
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- if oral temperature cannot be obtained
- abnormal aminotransferase levels
- prior adverse reaction to acetaminophen or N-acetylcysteine
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: Acetaminophen in Combination With N-Acetylcysteine (NAC) vs. Placebo in the Treatment of Fever: A Double-Blind, Randomized Control Study
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.
Read the 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.
- Conditions
- Liver Failure, Liver Failure, Acute, Drug Induced Liver Injury, Prevention & Control, Fever
- Being tested
- APAP and NAC combination, APAP and Placebo
- Keywords
- Acetaminophen, Acetylcysteine, Antidotes
- Medical subject headings
- Liver Failure, Liver Failure, Acute, Chemical and Drug Induced Liver Injury, Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APAP and NAC combinationDrug
Also called APAP: n-acetyl-p-aminophenol; acetaminophen; Tylenol, NAC: n-acetylcysteine; Mucomyst
APAP 650mg and NAC 600mg combination oral tablet administered once
APAP and PlaceboDrug
Also called APAP: n-acetyl-p-aminophenol; acetaminophen; Tylenol
APAP 650mg and Placebo combination oral tablet administered once
| Study group | Role | What they receive |
|---|---|---|
| APAP and NAC combination | Experimental | N-acetyl-p-aminophenol and placebo (APAP-NAC) combination pill Receives: Drug: APAP and NAC combination |
| APAP and Placebo combination | Placebo comparator | N-acetyl-p-aminophenol and placebo (APAP-placebo) combination pill Receives: Drug: APAP and Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in temperature reduction between participants who are administered combination N-acetyl-p-aminophenol and N-Acetylcysteine (APAP-NAC) versus combination APAP-placebo
Measured: 6 hours after study drug administration
Secondary outcomes (1)
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.
Measured: Within 24 hours of study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2010 (estimated)
- Study startApr 2009
Why it stopped: Unable to recruit sufficient participants due to lack of funding; PI has left the institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Liver FailureStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthew Chang, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01137591
- Sponsor's protocol ID
- AAAD4090
- Status last verified
- Mar 2015
- First submitted
- 3 Jun 2010
- Last updated
- 5 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 18163234Smilkstein 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.
PubMed 3059186Vale 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.
PubMed 7658783
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acetaminophen in Combination With N-Acetylcysteine (NAC) vs. Placebo in the Treatment of Fever: A Double-Blind, Randomized Control Study
- ClinicalTrials.gov ID
- NCT01137591
- Acronym / sponsor ID
- AAAD4090
- Conditions
- Liver Failure, Liver Failure, Acute, Drug Induced Liver Injury, Prevention & Control, Fever
- Keywords
- Acetaminophen, Acetylcysteine, Antidotes
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Unable to recruit sufficient participants due to lack of funding; PI has left the institution.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Apr 2009
- First posted
- 4 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| APAP and NAC combination | Experimental | Drug: APAP and NAC combinationN-acetyl-p-aminophenol and placebo (APAP-NAC) combination pill |
| APAP and Placebo combination | Placebo comparator | Drug: APAP and PlaceboN-acetyl-p-aminophenol and placebo (APAP-placebo) combination pill |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- if oral temperature cannot be obtained
- abnormal aminotransferase levels
- prior adverse reaction to acetaminophen or N-acetylcysteine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APAP and NAC combinationAlso: APAP: n-acetyl-p-aminophenol; acetaminophen; Tylenol, NAC: n-acetylcysteine; MucomystAPAP 650mg and NAC 600mg combination oral tablet administered once | Drug | APAP and NAC combination |
| APAP and PlaceboAlso: APAP: n-acetyl-p-aminophenol; acetaminophen; TylenolAPAP 650mg and Placebo combination oral tablet administered once | Drug | APAP and Placebo combination |
Primary outcome
Difference in temperature reduction between participants who are administered combination N-acetyl-p-aminophenol and N-Acetylcysteine (APAP-NAC) versus combination APAP-placebo
Time frame: 6 hours after study drug administration
1 secondary outcome
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
Time frame: Within 24 hours of study drug administration
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2015.
- Background: PubMed 18163234Bronstein 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.
- Background: PubMed 3059186Smilkstein 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.
- Background: PubMed 7658783Vale 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.
- Acetaminophen overdose information from the NIHLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Chang, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing APAP and NAC combination in people with Liver Failure and Liver Failure, Acute, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in temperature reduction between participants who are administered combination N-acetyl-p-aminophenol and N-Acetylcysteine (APAP-NAC) versus combination APAP-placebo (time frame: 6 hours after study drug administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01137591, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2015.