Safety and Efficacy Study of a New Formulation of Acetylcysteine Injection

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ClinicalTrials.gov Identifier: NCT01118663

Recruitment Status : Terminated

First Posted : May 7, 2010

Results First Posted : August 4, 2014

Last Update Posted : August 4, 2014

Sponsor:

Information provided by (Responsible Party):

Cumberland Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acetaminophen Overdose	Drug: Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free) Drug: Acetadote	Phase 3

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	17 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Multi-center, Double-blind, Randomized, Controlled Study to Determine the Efficacy and Safety of a New Formulation of Acetylcysteine Injection
Study Start Date :	September 2010
Actual Primary Completion Date :	November 2012
Actual Study Completion Date :	May 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Edetic acid Sodium calcium edetate Pentetic acid Edetate Sodium Acetylcysteine Edetate disodium Edetate calcium disodium Pentetate Calcium Trisodium ZnDTPA

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Acetadote without EDTA Acetadote EF [Ethylenediaminetetraacetic Acid (EDTA) - Free]	Drug: Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free) Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free) {new formulation} 200 mg/kg in 1000 ml diluent over 4 hours; then 100 mg/kg in 1000 ml diluent over 16 hours Other Name: acetylcysteine
Active Comparator: Acetadote Acetadote [Old formulation containing EDTA]	Drug: Acetadote Acetadote [old formulation] 150 mg/kg in 200 mL diluent over 60 minutes; then Acetadote 50 mg/kg in 500 mL diluent over 4 hours; then Acetadote 100 mg/kg in 1000 mL diluent over 16 hours. Other Name: acetylcysteine

Outcome Measures

Primary Outcome Measures :

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 [ Time Frame: 21 hours ]
Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.

Secondary Outcome Measures :

To Evaluate the Percentage of Subjects Requiring Continued Therapy [ Time Frame: 21 hours ]
Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.
To Evaluate the Incidence of Clinical Need for Therapy Beyond the Current 21 Hour FDA Approved Dosing Regimen. [ Time Frame: 42 hours ]
Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.
To Evaluate the Incidence of Treatment Emergent Adverse Events [ Time Frame: 21-42 hours ]
To Evaluate the Incidence of Anaphylactoid Reaction. [ Time Frame: 1 hour ]
Data analysis was conducted on the subjects enrolled in the study prior to study termination. Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.

Eligibility Criteria

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Ages Eligible for Study:	12 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

History of allergy or hypersensitivity to acetylcysteine or any component of Acetadote.
Exposed to investigational drugs within 30 days before Clinical Trial Material (CTM) administration.
Pregnant or nursing.
Less than 12 years of age.
Have a baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1000 U/L.
Have a baseline International Normalized. Ratio (INR) > 2.0
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.
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.
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).
Refusal to provide written authorization for use and disclosure of protected health information.
Be otherwise unsuitable for the study, in the opinion of the Investigator.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01118663

Locations

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United States, Arizona
Maricopa Medical Center
Phoenix, Arizona, United States, 85008
United States, California
Loma Linda University Medical Center
Loma Linda, California, United States, 92350
University of California Irvine Medical Center
Orange, California, United States, 92868
UCSD Medical Center
San Diego, California, United States, 92103
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
Denver Health and Hospital Authority
Denver, Colorado, United States, 80204
United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 06102
United States, Louisiana
LSU Health Sciences Center - Shreveport
Shreveport, Louisiana, United States, 71130
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
UMass Memorial Medical Center
Worcester, Massachusetts, United States, 01655
United States, Michigan
Spectrum Health Butterworth Hospital
Grand Rapids, Michigan, United States, 44506
United States, North Carolina
East Carolina University Medical Center
Greenville, North Carolina, United States, 27834
United States, Ohio
Toledo Hospital
Toledo, Ohio, United States, 43606
United States, Texas
Scott & White Medical Center
Temple, Texas, United States, 76508

Sponsors and Collaborators

Cumberland Pharmaceuticals

Investigators

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Study Director:	Art Wheeler, MD	Cumberland Pharmaceuticals, Inc.

More Information

Publications:

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.

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.

Kimura M, Kawada A. Contact dermatitis due to trisodium ethylenediaminetetra-acetic acid (EDTA) in a cosmetic lotion. Contact Dermatitis. 1999 Dec;41(6):341.

Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des. 2004;10(29):3639-49. Review.

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Responsible Party:	Cumberland Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01118663
Other Study ID Numbers:	CPI-NAC-001
First Posted:	May 7, 2010 Key Record Dates
Results First Posted:	August 4, 2014
Last Update Posted:	August 4, 2014
Last Verified:	August 2014

Keywords provided by Cumberland Pharmaceuticals:


Acetaminophen overdose; induced hepatotoxicity, liver injury

Additional relevant MeSH terms:

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Drug Overdose Substance-Related Disorders Chemically-Induced Disorders Acetylcysteine Edetic Acid N-monoacetylcystine Pentetic Acid Antiviral Agents Anti-Infective Agents Expectorants Respiratory System Agents	Free Radical Scavengers Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Physiological Effects of Drugs Antidotes Anticoagulants Calcium Chelating Agents Chelating Agents Sequestering Agents Iron Chelating Agents

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