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

dc.contributor.authorTu, Wanzhu
dc.contributor.authorGawrieh, Samer
dc.contributor.authorDasarathy, Srinivasan
dc.contributor.authorMitchell, Mack C.
dc.contributor.authorSimonetto, Douglas A.
dc.contributor.authorPatidar, Kavish R.
dc.contributor.authorMcClain, Craig J.
dc.contributor.authorBataller, Ramon
dc.contributor.authorSzabo, Gyongyi
dc.contributor.authorTang, Qing
dc.contributor.authorBarton, Bruce A.
dc.contributor.authorRadaeva, Svetlana
dc.contributor.authorSanyal, Arun J.
dc.contributor.authorShah, Vijay
dc.contributor.authorAlcoholic Hepatitis Network (AlcHepNet) Investigators
dc.contributor.departmentBiostatistics, School of Public Health
dc.date.accessioned2023-10-17T16:28:08Z
dc.date.available2023-10-17T16:28:08Z
dc.date.issued2023-01-18
dc.description.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.
dc.eprint.versionFinal published version
dc.identifier.citationTu W, Gawrieh S, Dasarathy S, et al. Design of a multicenter randomized clinical trial for treatment of Alcohol-Associated Hepatitis. Contemp Clin Trials Commun. 2023;32:101074. Published 2023 Jan 18. doi:10.1016/j.conctc.2023.101074
dc.identifier.urihttps://hdl.handle.net/1805/36395
dc.language.isoen_US
dc.publisherElsevier
dc.relation.isversionof10.1016/j.conctc.2023.101074
dc.relation.journalContemporary Clinical Trials Communications
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.sourcePMC
dc.subjectMulticenter clinical trial
dc.subjectAlcohol-associated hepatitis
dc.subjectPrednisone
dc.subjectAnakinra
dc.subjectZinc sulfate
dc.subjectModel for end-stage liver disease (MELD)
dc.titleDesign of a multicenter randomized clinical trial for treatment of Alcohol-Associated Hepatitis
dc.typeArticle
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