N-acetylcysteine in Non-Acetaminophen Pediatric Acute Liver Failure
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| ClinicalTrials.gov Identifier: NCT00248625 |
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Recruitment Status :
Completed
First Posted : November 4, 2005
Results First Posted : July 28, 2016
Last Update Posted : July 28, 2016
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Sponsor:
University of Pittsburgh
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Robert Squires, Jr., University of Pittsburgh
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Brief Summary:
We have completed patient enrollment in the the double blind, randomized, placebo-controlled trial of intravenous (IV) N-acetylcysteine (NAC) vs. placebo for the treatment of non-acetaminophen ALF. The purpose of this study is to examine the safety and efficacy of intravenous NAC in children with ALF for whom no antidote or other specific treatment is available. Inclusion in the NAC Study required enrollment in the Pediatric Acute Liver Failure (PALF) Study Registry.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Liver Failure Hepatic Encephalopathy | Drug: N-acetylcysteine Drug: Placebo | Phase 3 |
The Pediatric Acute Liver Failure (PALF) Study Group to identify, characterize, and develop management strategies for infants, children and adolescents who present with acute liver failure. The PALF study group includes 20 sites (17 in the United States, 2 in the United Kingdom, and 1 in Canada). The primary objective of the Pediatric Acute Liver Failure (PALF) study is to collect, maintain, analyze, and report clinical, epidemiological, and outcome data in children with ALF, including information derived from biospecimens.
Patients enrolled in the PALF study registry were able to enroll in the NAC study providing they met the additional required inclusion/exclusion criteria.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 184 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Multi-center Study of the Safety and Efficacy of N-acetylcysteine in the Treatment of Acute Liver Failure in Pediatric Patients Not Caused by Acetaminophen. |
| Study Start Date : | January 2000 |
| Actual Primary Completion Date : | September 2009 |
| Actual Study Completion Date : | October 2010 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Acetylcysteine
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: N-acetylcysteine (NAC)
Eligible children were adaptively allocated by age (less than 2 years of age or at least 2 years old) and hepatic encephalopathy (grade 0-1 or 2-4) to receive N-acetylcysteine (150 mg/kg/d) in 5% dextrose (D5W) infused over 24 hours for up to 7 consecutive days
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Drug: N-acetylcysteine
The study drug is administered as a continuous infusion at a dose of 150 mg/kg/day for up to 7 days following entry into the study. The infusion is discontinued at the time of death, liver transplant or discharge.
Other Name: Mucomyst |
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Placebo Comparator: placebo
Eligible children were adaptively allocated within strata defined by age (less than 2 years of age or at least 2 years old) and hepatic encephalopathy (grade 0-1 or 2-4) to receive 5% dextrose (D5W) infused over 24 hours for up to 7 consecutive
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Drug: Placebo
Eligible children were adaptively allocated within strata defined by age (less than 2 years of age or at least 2 years old) and hepatic encephalopathy (grade 0-1 or 2-4) to receive N-acetylcysteine (150 mg/kg/d) in 5% dextrose (D5W) and water or placebo consisting of an equal volume of D5W alone. Volumes were adjusted for small children. Study medications were infused over 24 hours for up to 7 consecutive days in a dedicated line without other medications. Treatment was stopped earlier than 7 days in the case of hospital discharge, liver transplantation, or death within 7 days of randomization.
Other Name: dextrose in water |
Primary Outcome Measures :
- Survival [ Time Frame: One year following randomization ]Spontaneous survival without transplant plus survival following transplantation
Secondary Outcome Measures :
- Spontaneous Recovery [ Time Frame: One year following randomization ]Survival without liver transplantation
- Cumulative Percent Incidence of Transplantation by 1 Year [ Time Frame: Within 1 year of randomization ]
- Length of Hospital Stay [ Time Frame: Randomization to hospital discharge ]
- Categorized Length of ICU Stay [ Time Frame: Within 7 days of randomization ]The length of ICU stay was categorized as number of days in ICU within 7 days of randomization, unless participant either died or received an LTx within this time period. Special categories were created for these cases.
- Number of Organ Systems Failing [ Time Frame: Within 7 days of randomization ]
- Highest Coma Grade of Hepatic Encephalopathy [ Time Frame: Within 7 days of randomization ]West Haven Criteria for hepatic encephalopathy (Grade 0 - IV ) is used for participants > 3 year of age. Coma grade IV indicates a participant who is comatose , with no reflexes, is decerebrate and has abnormal EEG changes with very slow delta activity. For participants less than 3 years the Whittington Scale was used. The Whittington scale does not use EEG changes and has only 3 levels, early (grades I and II), Mid (III) with somnolence, stupor, combativeness and Late (IV) for participants who are comatose with absent reflexes and decerebrate or decorticate posturing.
- Infectious Complication [ Time Frame: Within 7 days of randomization ]
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| Ages Eligible for Study: | up to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Meet entry criteria for and be enrolled in the Pediatric Acute Liver Failure prospective database.
- Able to be evaluated and initiate treatment within the first 24 hours of hospitalization
- Patients transferred from referring hospitals to the study site may be considered for enrollment, provided that no other treatment protocol has begun, and that no liver support device (BAL, extracorporeal liver assist device, transgenic pig perfusion) has been used or is contemplated.
- Use of fresh frozen plasma infusions will not disqualify patients from participation.
Exclusion Criteria:
- older than 18 years of age
- pregnancy
- ALF that is secondary to acute acetaminophen toxicity, mushroom poisoning, or a known malignancy.
- Patients who exhibit signs of cerebral herniation, have intractable arterial hypotension, require inotropic drugs, or demonstrate signs of sepsis (temperature ≥ 39.5o C or bacteremia) at the time of enrollment
- No exclusion will be made on the basis of race, ethnic group or gender.
- Criteria for inclusion of females and minorities will be those established in the NIH guidelines
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): NCT00248625
Locations
Show 20 study locations
Sponsors and Collaborators
University of Pittsburgh
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
| Principal Investigator: | Robert H Squires, M.D. | Children's Hospital of Pittsburgh, University of Pittsburgh |
Publications:
| Responsible Party: | Robert Squires, Jr., MD, University of Pittsburgh |
| ClinicalTrials.gov Identifier: | NCT00248625 |
| Other Study ID Numbers: |
IRB #: 0608007 U01DK072146 ( U.S. NIH Grant/Contract ) |
| First Posted: | November 4, 2005 Key Record Dates |
| Results First Posted: | July 28, 2016 |
| Last Update Posted: | July 28, 2016 |
| Last Verified: | June 2016 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
Keywords provided by Robert Squires, Jr., University of Pittsburgh:
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acute liver failure hepatic encephalopathy acetaminophen toxicity N-acetylcysteine |
Additional relevant MeSH terms:
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Liver Failure Hepatic Insufficiency Hepatic Encephalopathy Liver Failure, Acute Brain Diseases Central Nervous System Diseases Nervous System Diseases Liver Diseases Digestive System Diseases Brain Diseases, Metabolic Metabolic Diseases Acetylcysteine |
N-monoacetylcystine 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 |