Clinical trial NCT01118663: Safety and Efficacy Study of a New Formulation of Acetylcysteine Injection
Official title: A Multi-center, Double-blind, Randomized, Controlled Study to Determine the Efficacy and Safety of a New Formulation of Acetylcysteine Injection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Acetaminophen Overdose
Keywords: Acetaminophen overdose; induced hepatotoxicity, liver injury
Lead sponsor: Cumberland Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2010-05-07
Enrollment: 17
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is determine if a new formulation of Acetadote is at least as effective as the current formulation in the prevention and treatment of acetaminophen overdose related liver injury.

Detailed description: The primary objective of this study is to demonstrate non-inferiority of efficacy determined by the proportion of subjects who develop hepatotoxicity when treated with a new formulation of Acetadote and the proposed new dosing regimen compared to the rate of hepatotoxicity with the current formulation of Acetadote and the current dosing regimen.

Eligibility criteria: Inclusion Criteria:

1) Any subject requiring treatment with acetylcysteine for acute acetaminophen toxicity

Exclusion Criteria:

1. History of allergy or hypersensitivity to acetylcysteine or any component of Acetadote.
2. Exposed to investigational drugs within 30 days before Clinical Trial Material (CTM) administration.
3. Pregnant or nursing.
4. Less than 12 years of age.
5. Have a baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>1000 U/L.
6. Have a baseline International Normalized. Ratio (INR) \> 2.0
7. Be on dialysis or having existing renal injury such that the volume of the study drug administration would render the patient unsuitable for the study, in the opinion of the investigator.
8. Have congestive heart failure such that the volume of the study drug administration would render the patient unsuitable for the study, in the opinion of the investigator.
9. Inability to understand the requirements of the study. Subjects must be willing to provide written informed consent or consent of parent/legal guardian (as evidenced by signature on an informed consent document approved by an Institutional Review Board \[IRB\]), and agree to abide by the study restrictions. (If the subject is incapacitated, informed consent will be sought from a legally acceptable representative).
10. Refusal to provide written authorization for use and disclosure of protected health information.
11. Be otherwise unsuitable for the study, in the opinion of the Investigator.

Primary outcomes:
measure: The Incidence of Hepatoxicity as Measured by the Percentage of Subjects With an Alanine Transaminase (ALT) or Aspartate Transaminase (AST) Value > 1000 U/L Versus Those With an ALT and AST < 1000 U/L
timeFrame: 21 hours
Secondary outcomes:
measure: To Evaluate the Percentage of Subjects Requiring Continued Therapy
timeFrame: 21 hours
measure: To Evaluate the Incidence of Clinical Need for Therapy Beyond the Current 21 Hour FDA Approved Dosing Regimen.
timeFrame: 42 hours
measure: To Evaluate the Incidence of Treatment Emergent Adverse Events
timeFrame: 21-42 hours
measure: To Evaluate the Incidence of Anaphylactoid Reaction.
timeFrame: 1 hour
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Maricopa Medical Center
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: San Diego
country: United States
facility: UCSD Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Denver
country: United States
facility: Denver Health and Hospital Authority
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Shreveport
country: United States
facility: LSU Health Sciences Center - Shreveport
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health Butterworth Hospital
state: Michigan
city: Greenville
country: United States
facility: East Carolina University Medical Center
state: North Carolina
city: Toledo
country: United States
facility: Toledo Hospital
state: Ohio
city: Temple
country: United States
facility: Scott & White Medical Center
state: Texas
Study officials:
affiliation: Cumberland Pharmaceuticals, Inc.
name: Art Wheeler, MD
role: STUDY_DIRECTOR
References:
citation: Bhushan M, Beck MH. Allergic contact dermatitis from disodium ethylenediamine tetra-acetic acid (EDTA) in a local anaesthetic. Contact Dermatitis. 1998 Mar;38(3):183. doi: 10.1111/j.1600-0536.1998.tb05702.x. No abstract available.
citation: van Laar T, van Hilten B, Neef C, Rutgers AW, Pavel S, Bruijn JA. The role of EDTA in provoking allergic reactions to subcutaneous infusion of apomorphine in patients with Parkinson's disease: a histologic study. Mov Disord. 1998 Jan;13(1):52-5. doi: 10.1002/mds.870130113.
citation: Kimura M, Kawada A. Contact dermatitis due to trisodium ethylenediaminetetra-acetic acid (EDTA) in a cosmetic lotion. Contact Dermatitis. 1999 Dec;41(6):341. doi: 10.1111/j.1600-0536.1999.tb06184.x. No abstract available.
citation: Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des. 2004;10(29):3639-49. doi: 10.2174/1381612043382846.