Acetaminophen OverdosePhase 3NCT01118663
Safety and Efficacy Study of a New Formulation of Acetylcysteine Injection
A Phase 3 study testing Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free) and Acetadote in people with Acetaminophen Overdose, run by Cumberland Pharmaceuticals at 14 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Acetaminophen Overdose
- What is being tested?
- Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free) and Acetadote
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 14 sitesUnited States
- Study dates
- Sep 2010to May 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 1) Any subject requiring treatment with acetylcysteine for acute acetaminophen toxicity
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
University of Colorado Hospital
Aurora, Colorado, 80045
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Denver Health and Hospital Authority
Denver, Colorado, 80204
Spectrum Health Butterworth Hospital
Grand Rapids, Michigan, 44506
East Carolina University Medical Center
Greenville, North Carolina, 27834
Hartford Hospital
Hartford, Connecticut, 06102
Loma Linda University Medical Center
Loma Linda, California, 92350
University of California Irvine Medical Center
Orange, California, 92868
Maricopa Medical Center
Phoenix, Arizona, 85008
UCSD Medical Center
San Diego, California, 92103
LSU Health Sciences Center - Shreveport
Shreveport, Louisiana, 71130
Scott & White Medical Center
Temple, Texas, 76508
Toledo Hospital
Toledo, Ohio, 43606
UMass Memorial Medical Center
Worcester, Massachusetts, 01655
About this study
Official title: A Multi-center, Double-blind, Randomized, Controlled Study to Determine the Efficacy and Safety of a New Formulation of Acetylcysteine Injection
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.
Read the 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.
- Conditions
- Acetaminophen Overdose
- Being tested
- Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free), Acetadote
- Keywords
- Acetaminophen overdose; induced hepatotoxicity, liver injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free)Drug
Also called acetylcysteine
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
AcetadoteDrug
Also called acetylcysteine
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.
| Study group | Role | What they receive |
|---|---|---|
| Acetadote without EDTA | Experimental | Acetadote EF [Ethylenediaminetetraacetic Acid (EDTA) - Free] Receives: Drug: Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free) |
| Acetadote | Active comparator | Acetadote [Old formulation containing EDTA] Receives: Drug: Acetadote |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.
Measured: 21 hours
Secondary outcomes (4)
To Evaluate the Percentage of Subjects Requiring Continued Therapy
Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.
Measured: 21 hours
To Evaluate the Incidence of Clinical Need for Therapy Beyond the Current 21 Hour FDA Approved Dosing Regimen.
Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.
Measured: 42 hours
To Evaluate the Incidence of Treatment Emergent Adverse Events
Measured: 21-42 hours
To Evaluate the Incidence of Anaphylactoid Reaction.
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.
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2010 (estimated)
- Study startSep 2010
- Primary completionNov 2012
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Acetaminophen OverdoseStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cumberland Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Art Wheeler, MD, Study director, Cumberland Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01118663
- Sponsor's protocol ID
- CPI-NAC-001
- Status last verified
- Aug 2014
- First submitted
- 4 May 2010
- Last updated
- 4 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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. doi: 10.1111/j.1600-0536.1998.tb05702.x. No abstract available.
PubMed 9536427van 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.
PubMed 9452326Kimura 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.
PubMed 10617216Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des. 2004;10(29):3639-49. doi: 10.2174/1381612043382846.
PubMed 15579060
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Double-blind, Randomized, Controlled Study to Determine the Efficacy and Safety of a New Formulation of Acetylcysteine Injection
- ClinicalTrials.gov ID
- NCT01118663
- Acronym / sponsor ID
- CPI-NAC-001
- Conditions
- Acetaminophen Overdose
- Keywords
- Acetaminophen overdose; induced hepatotoxicity, liver injury
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Cumberland PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Sep 2010
- Primary completion
- Nov 2012 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 7 May 2010 (estimated)
- Results
- Posted 4 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acetadote without EDTA | Experimental | Drug: Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free)Acetadote EF [Ethylenediaminetetraacetic Acid (EDTA) - Free] |
| Acetadote | Active comparator | Drug: AcetadoteAcetadote [Old formulation containing EDTA] |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 1) Any subject requiring treatment with acetylcysteine for acute acetaminophen toxicity
Key exclusion criteria (11 listed)
- 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.
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 |
|---|---|---|
| Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free)Also: acetylcysteineAcetadote 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 | Drug | Acetadote without EDTA |
| AcetadoteAlso: acetylcysteineAcetadote [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. | Drug | Acetadote |
Primary outcome
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.
4 secondary outcomes
To Evaluate the Percentage of Subjects Requiring Continued Therapy
Time frame: 21 hours
To Evaluate the Incidence of Clinical Need for Therapy Beyond the Current 21 Hour FDA Approved Dosing Regimen.
Time frame: 42 hours
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9536427Bhushan 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.
- Background: PubMed 9452326van 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.
- Background: PubMed 10617216Kimura 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.
- Background: PubMed 15579060Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des. 2004;10(29):3639-49. doi: 10.2174/1381612043382846.
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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.
Art Wheeler, MD study director
Cumberland Pharmaceuticals
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free) and Acetadote in people with Acetaminophen Overdose, run by Cumberland Pharmaceuticals at 14 sites 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 1 inclusion and 11 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: stopped early, as of the sponsor's last update on 4 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
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). 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 NCT01118663, which also lists 4 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 4 Aug 2014.