Title

Design and rationale of a multicenter defeat alcoholic steatohepatitis trial: (DASH) randomized clinical trial to treat alcohol-associated hepatitis

UMMS Affiliation

Department of Population and Quantitative Health Sciences

Publication Date

2020-09-01

Document Type

Article

Disciplines

Clinical Trials | Digestive System Diseases | Health Services Research

Abstract

BACKGROUND/AIMS: Despite high mortality of alcohol-associated hepatitis, there has been limited advancement in treatment strategies. Defeat Alcoholic Steatohepatitis (DASH) is a multicenter, randomized, double-blind controlled trial whose primary objective was to evaluate the safety and efficacy of a novel combination of 3 drugs targeting different perturbations in AH.

METHODS: Severe AH was diagnosed by liver biopsy or clinical and biochemical criteria and model for end stage liver disease (MELD) score > /= 20 stratified by MELD scores (20-25 and > /= 26) and randomized to a combination of an interleukin receptor 1 antagonist, Anakinra(100 mg daily for 14 days) to suppress acute inflammation, pentoxifylline (400 mg three times a day for 28 days) to prevent hepatorenal syndrome, and zinc sulfate (220 mg orally once daily for 6 months) or the standard of care therapy including methylprednisolone 32 mg orally once daily for 28 days. The primary efficacy outcome was the unadjusted log-rank test of the Kaplan-Meier survival estimates for the two treatment groups at 180 days.

RESULTS: Between July 2012 to March 2018, 500 subjects with severe AH were screened of which 104 subjects were enrolled with MELD score of 25.6 +/- 3.2 (20.0-35.0) in the investigational arm and 25.8 +/- 4.5 (20.0-40.0) in the standard of care arm. Causes of screen failures included not meeting eligibility criteria (n = 347), declining to participate (n = 39), and other reasons (n = 10).

CONCLUSIONS: Data from the DASH consortium studies will determine if a combination of drugs targeting multiple mechanisms of injury in the severe AH will improve clinical outcomes.

DOI of Published Version

10.1016/j.cct.2020.106094

Source

Dasarathy S, Mitchell MC, Barton B, McClain CJ, Szabo G, Nagy LE, Radaeva S, McCullough AJ. Design and rationale of a multicenter defeat alcoholic steatohepatitis trial: (DASH) randomized clinical trial to treat alcohol-associated hepatitis. Contemp Clin Trials. 2020 Sep;96:106094. doi: 10.1016/j.cct.2020.106094. Epub 2020 Jul 31. PMID: 32739495; PMCID: PMC7494528. Link to article on publisher's site

Journal/Book/Conference Title

Contemporary clinical trials

PubMed ID

32739495

Related Resources

Link to Article in PubMed

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