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

NCT ID: NCT01455337

Last Updated: 2011-10-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2011-12-31

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.

Conditions

Alcoholic Hepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

prednisolone

Group Type: ACTIVE_COMPARATOR

Prednisolone

Intervention Type: DRUG

40mg qd

pentoxifylline

Group Type: EXPERIMENTAL

pentoxifylline

Intervention Type: DRUG

400mg tid

Interventions

pentoxifylline

400mg tid

Intervention Type: DRUG

Prednisolone

40mg qd

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Inje University

OTHER

Sponsor Role: lead

Responsible Party

Seung Ha Park

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

1111

Identifier Type: -

Identifier Source: org_study_id