Short-term Survival in Patients With Severe Alcoholic Hepatitis Treated With Steroid Versus Pentoxifylline

This study is enrolling participants by invitation only.
Information provided by (Responsible Party):
Seung Ha Park, Inje University Identifier:
First received: October 13, 2011
Last updated: October 18, 2011
Last verified: October 2011

Alcoholic hepatitis represents one of the more serious forms of alcoholic liver disease. Critically ill patients with alcoholic hepatitis have high morbidity and mortality rate. Because of data suggesting that the pathogenic mechanisms in alcoholic hepatitis involve cytokine release and the perpetuation of injury by immunologic process, corticosteroid has been extensively evaluated in the treatment of alcoholic hepatitis. Although there are discrepancies in literature as several randomized trials and meta-analyses have reached contradictory results, corticosteroid for a subset of patients with severe alcoholic hepatitis, defined as a discriminant function ≥ 32, who also have no concomitant gastrointestinal bleeding, active infection, renal failure, and pancreatitis, has been recommended. This latter point emphasizes the important of meticulous selection to avoid the side effects of corticosteroid. Thus, the beneficial effects seems confined to a highly selected minority group in which the inhibitory effect of corticosteroid on liver inflammation is not outweighed by side effects such as weakened defense against infection, anti-anabolic effects, and possible ulcer-promoting effects causing gastrointestinal bleeding, which may be deleterious in these critically ill patients.

Newer understanding of the role of the role of TNF-α expression and receptor activity in alcoholic liver injury has prompted to an examination of TNF inhibition as an alternative to corticosteroid for severe alcoholic hepatitis. Pentoxifylline, a nonspecific TNF inhibitor, recently has been demonstrated in a randomized trial to improve survival in the therapy of severe alcoholic hepatitis. In particular, the survival benefit of pentoxifylline appears to be related to a significant reduction in development of hepatorenal syndrome. These results are promising, and support the need to further evaluate the potential of this new therapeutic avenue.

There is a need for head to head comparison of corticosteroid and pentoxifylline in severe alcoholic hepatitis. At the time the current study was designed (2008), corticosteroid was first-line treatment for severe alcoholic hepatitis. This study was designed to demonstrate that the effect of pentoxifylline was similar (i.e., not inferior) to that of prednisolone, an active form of prednisone. The aim of the present study was thus to compare the effects of pentoxifylline and prednisolone on the short-term mortality.

Condition Intervention Phase
Alcoholic Hepatitis
Drug: pentoxifylline
Drug: Prednisolone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: Principal Investigator

Resource links provided by NLM:

Further study details as provided by Inje University:

Primary Outcome Measures:
  • survival rate [ Time Frame: at 1-month ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 126
Study Start Date: January 2009
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: prednisolone Drug: Prednisolone
40mg qd
Experimental: pentoxifylline Drug: pentoxifylline
400mg tid


Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Clinical diagnosis of Severe alcoholic hepatitis (discriminant function ≥ 32 points), Must be able to swallow tablets.

Exclusion Criteria:

  • Gastrointestinal bleeding Bacterial infection HBsAg positivity Acute pancreatitis
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No Contacts or Locations Provided
  More Information

Responsible Party: Seung Ha Park, MD, Inje University Identifier: NCT01455337     History of Changes
Other Study ID Numbers: 1111 
Study First Received: October 13, 2011
Last Updated: October 18, 2011
Health Authority: Korea: Food and Drug Administration

Keywords provided by Inje University:
severe alcoholic hepatitis

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Hepatitis A
Alcohol-Induced Disorders
Alcohol-Related Disorders
Chemically-Induced Disorders
Digestive System Diseases
Enterovirus Infections
Hepatitis, Viral, Human
Liver Diseases
Liver Diseases, Alcoholic
Picornaviridae Infections
RNA Virus Infections
Substance-Related Disorders
Virus Diseases
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Enzyme Inhibitors processed this record on May 26, 2016