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

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.