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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Alcoholic Hepatitis	Drug: pentoxifylline; Drug: Prednisolone	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	126 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Investigator)
Primary Purpose:	Treatment
Official Title:	Principal Investigator
Study Start Date :	January 2009
Estimated Primary Completion Date :	December 2011
Estimated Study Completion Date :	December 2011

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: prednisolone	Drug: Prednisolone; 40mg qd
Experimental: pentoxifylline	Drug: pentoxifylline; 400mg tid

Outcome Measures

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Primary Outcome Measures :

1. survival rate [ Time Frame: at 1-month ]

Eligibility Criteria

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Ages Eligible for Study:	20 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

No Contacts or Locations Provided

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Seung Ha Park, MD, Inje University
ClinicalTrials.gov Identifier:	NCT01455337 History of Changes
Other Study ID Numbers:	1111
First Posted:	October 19, 2011
Last Update Posted:	October 19, 2011
Last Verified:	October 2011

Keywords provided by Seung Ha Park, Inje University:

severe alcoholic hepatitis

Additional relevant MeSH terms:

Hepatitis, Alcoholic; Hepatitis; Hepatitis A; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders	Prednisolone acetate; Methylprednisolone acetate; Prednisolone; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone hemisuccinate; Prednisolone phosphate; Pentoxifylline; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents