Design of a multicenter randomized clinical trial for treatment of Alcohol-Associated Hepatitis
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Mitchell, Mack C
Simonetto, Douglas A
Patidar, Kavish R
McClain, Craig J
Barton, Bruce A
Sanyal, Arun J
UMass Chan AffiliationsPopulation and Quantitative Health Sciences
Document TypeJournal Article
Model for end-stage liver disease (MELD)
Multicenter clinical trial
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AbstractBackground: Mortality is high for severe alcohol-associated hepatitis (AH). Corticosteroids are the standard of care for patients without contraindications. Recent data showed that interleukin-1β receptor antagonist anakinra attenuated inflammation and liver damage. We designed a multicenter, double-blind, randomized controlled trial to assess the safety and efficacy of anakinra compared to prednisone. Methods: Patients meeting the clinical and biochemical criteria for severe AH with MELD scores between 20 and 35 were recruited at eight clinical sites. Eligible patients enrolled in the study were randomized to anakinra, 100 mg subcutaneous injection for 14 days, plus zinc sulfate 220 mg for 90 days, vs. prednisone 40 mg PO daily for 30 days. Matching placebos for anakinra, zinc, and prednisone were provided to mask the treatment. Participants were followed for 180 days. The primary outcome was overall survival at 90 days. An unadjusted log-rank test was used to compare the survival of the two treatments in the first 90 days. Between July 10, 2020, and March 4, 2022, we screened 1082 patients with severe AH, and 147 eligible patients were enrolled and randomized. The average baseline MELD score was 25 [range 20-35], Maddrey discriminant function (MDF) was 59.4 [range 20.2-197.5]. The mean aspartate transaminase (AST)-to-alanine transaminase (ALT) ratio was 3.5. The baseline characteristics were not statistically different between the two treatment groups. Conclusions: The study provided a direct comparison of the survival benefits and safety profiles of anakinra plus zinc vs. prednisone in patients with severe AH.
SourceTu W, Gawrieh S, Dasarathy S, Mitchell MC, Simonetto DA, Patidar KR, McClain CJ, Bataller R, Szabo G, Tang Q, Barton BA, Radaeva S, Sanyal AJ, Shah V; Alcoholic Hepatitis Network (AlcHepNet) Investigators. Design of a multicenter randomized clinical trial for treatment of Alcohol-Associated Hepatitis. Contemp Clin Trials Commun. 2023 Jan 18;32:101074. doi: 10.1016/j.conctc.2023.101074. PMID: 36698742; PMCID: PMC9869411.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/51840
Rights© 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/).; Attribution-NonCommercial-NoDerivatives 4.0 International
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Except where otherwise noted, this item's license is described as © 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/).