Design of a multicenter randomized clinical trial for treatment of Alcohol-Associated Hepatitis.

Autor:	Tu W; Indiana University School of Medicine, USA., Gawrieh S; Indiana University School of Medicine, USA., Dasarathy S; Cleveland Clinic, USA., Mitchell MC; University of Texas Southwestern Medical Center, USA., Simonetto DA; Mayo Clinic, USA., Patidar KR; Indiana University School of Medicine, USA., McClain CJ; University of Louisville Medical Center, USA., Bataller R; University of Pittsburgh, USA., Szabo G; Harvard Medical School, USA., Tang Q; Indiana University School of Medicine, USA., Barton BA; University of Massachusetts Chan Medical School, USA., Radaeva S; National Institute of Alcohol Abuse and Alcoholism, USA., Sanyal AJ; Virginia Commonwealth University, USA., Shah V; Mayo Clinic, USA.
Jazyk:	angličtina
Zdroj:	Contemporary clinical trials communications [Contemp Clin Trials Commun] 2023 Jan 18; Vol. 32, pp. 101074. Date of Electronic Publication: 2023 Jan 18 (Print Publication: 2023).
DOI:	10.1016/j.conctc.2023.101074
Abstrakt:	Background: 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. Competing Interests: Dr. Samer Gawrieh provides consulting services to TransMedics and Pfizer and he receives research grant support from Cirius, Viking, and Zydus. Dr. Vijay Shah serves on Advisory boards of Akaza Bioscience Ltd, AgomAb Therapeutics, Generon Shanghai, Intercept Pharmaceuticals, Inc, Mallinckrodt Pharmaceuticals, and Surrozen. He provides consulting services Ambys Medicines, Durect Corporation, HepaRegeniX, and Novartis Pharma AG. Dr. Mack Mitchell owns stocks in Amygdala Neuroscience and Advisory at Prodigy Biotech. Dr. Douglass Simonetto provides consulting services to BioVie and Mallinckrodt. Dr. Wanzhu Tu provides consulting services to Bayer. Dr. Gyongyi Szabo provides consulting services to Alnylam, Duret, Generon, Glympse Bio, Novartis, Quest Diagnostics, Surrozen, Terra Firma, and Zomagen. Dr. Arun Sanyal owns stocks in Sanyal Bio, Exhalenz, Conatus, Genfit, Duret, Indalo, and Tiziana. He provides consulting services to Conatus, Genfit, Gilead, Mallinckrodt Pharmaceuticals, Pfizer, BI, Novartis, Merck, Lilly, Novo Nordisk, Terns, Albireo, Sanofi, Jannsen, Takeda, Northsea, Poxel, 89Bio, NGM Bio, Amgen, Genentech, Roche, Madrigal, Inventiva, Covance, Prosciento, Histoindex, PathAI, and Biocellvia. Other authors declared no conflicts of interest. (© 2023 Published by Elsevier Inc.)
Databáze:	MEDLINE
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