Condition category
Digestive System
Date applied
12/05/2010
Date assigned
12/05/2010
Last edited
14/07/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Anil Dhawan

ORCID ID

Contact details

Department of Liver Studies and Transplantation
Strand
London
WC2R 2LS
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00248625

Protocol/serial number

6201

Study information

Scientific title

Acronym

PALF

Study hypothesis

Acute liver failure (ALF) is a rare form of liver disease in children. The condition leads to failure of the function of the liver in a child with no previous history of liver disease. The causative agents include infections, drugs and sometimes metabolic defects that present for the first time as liver failure. However, the cause of the liver failure could only be identified in one-third of the patients.

There is no accepted specific treatment for ALF other than general supportive measures such as maintenance of blood sugar levels, prevention of superadded infections, administration of blood products, measures to reduce brain swelling and assisted breathing in the intensive care unit. In patients with severe disesase, liver transplantation is the only effective treatment.

The purpose of this study is to test whether a drug called N-acetylcysteine (NAC) improves outcome of patients with ALF. This drug is used as an antidote in patients with paracetamol overdose who usually develop liver failure. This drug has been very helpful in improving the survival of patients where overdose is likely to be fatal. N-acetylcysteine reduces cell injury induced by oxidative stress in liver failure not only in liver but other organs also. In a small number of adults in our hospital with liver failure not related to paracetamol overdose an improvement in various parameters of body function like blood pressure and oxygen utilisation was observed after administration of NAC. This drug has also been shown to improve cell function in situations of multi-organ failure not caused by liver failure. However a more recent study from Edinburgh failed to demonstrate these observations. This drug has been used without a definitive evidence of its efficacy in few centres (including ours) in the management of liver failure. This multinational randomised controlled trial will help to establish the safety and efficacy of this drug.

Ethics approval

MREC approved (ref: 02-186)

Study design

Multicentre randomised interventional treatment trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Condition

Topic: Medicines for Children Research Network; Subtopic: All Diagnoses; Disease: All Diseases

Intervention

The study drug or placebo will be given as a 7-day continuous intravenous infusion to children with acute liver failure not due to acute acetaminophen toxicity.

Study drug: intravenous N-acetylcysteine
Total duration of therapy: 7 days. Duration may be less in the event of spontaneous recovery or liver transplantation.

Intervention type

Drug

Phase

Not Applicable

Drug names

N-acetylcysteine

Primary outcome measures

Comparison of survival without liver transplant

Secondary outcome measures

1. Length of intensive care unit and hospital stay
2. Number of organ systems failures

Overall trial start date

01/01/2003

Overall trial end date

01/12/2010

Reason abandoned

Eligibility

Participant inclusion criteria

Enrolment in PALF registry:
1. Evidence of acute liver injury
2. International normalised ratio (INR) greater than or equal to 1.5 or prothrombin time (PT) greater than or equal to 15 with encephalopathy, or INR greater than or equal to 2.0 or PT greater than or equal to 20 with or without encephalopathy
3. Aged less than 18 years, either sex
4. Informed consent, obtained from the patient or parent

Participant type

Patient

Age group

Child

Gender

Not Specified

Target number of participants

Planned sample size: 184; UK sample size: 28

Participant exclusion criteria

1. Acute paracetomol toxicity
2. Patient on N-acetylcysteine or received N-acetylcysteine during the course of this illness
3. Pregnancy
4. Known malignancy
5. Patient is on a liver support device
6. Sepsis
7. Signs of cerebral herniation
8. Intractable hypotension

Recruitment start date

01/01/2003

Recruitment end date

01/12/2010

Locations

Countries of recruitment

Canada, United Kingdom, United States of America

Trial participating centre

Department of Liver Studies and Transplantation
London
WC2R 2LS
United Kingdom

Sponsor information

Organisation

King's College Hospital NHS Foundation Trust (UK)

Sponsor details

Denmark Hill
London
SE5 9RS
United Kingdom

Sponsor type

Government

Website

http://www.kch.nhs.uk/

Funders

Funder type

Government

Funder name

National Institutes of Health (NIH) (USA)

Alternative name(s)

NIH

Funding Body Type

government organisation

Funding Body Subtype

federal/national government

Location

United States of America

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results in http://www.ncbi.nlm.nih.gov/pubmed/22886633

Publication citations

  1. Results

    Squires RH, Dhawan A, Alonso E, Narkewicz MR, Shneider BL, Rodriguez-Baez N, Olio DD, Karpen S, Bucuvalas J, Lobritto S, Rand E, Rosenthal P, Horslen S, Ng V, Subbarao G, Kerkar N, Rudnick D, Lopez MJ, Schwarz K, Romero R, Elisofon S, Doo E, Robuck PR, Lawlor S, Belle SH, , Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: a placebo-controlled clinical trial., Hepatology, 2013, 57, 4, 1542-1549, doi: 10.1002/hep.26001.

Additional files

Editorial Notes