Therapies for alcohol use disorder in alcohol-associated hepatitis clinical trials: Integrated trial design with a composite clinical outcome as the primary endpoint.

Abstract

Alcohol-associated hepatitis (AH) continues to have high morbidity and mortality. Despite rising incidence and health care utilization, there are no approved therapies for AH. Hazardous alcohol use is the underlying cause of AH and return to drinking influences the risk of AH recurrence and long-term survival in these patients. Yet, alcohol misuse is not directly targeted in clinical trials for AH. In this article, we discuss the conceptual basis, potential challenges, and approaches for designing integrated trials for AH that address both the alcohol misuse and liver injury components of the disease. We also provide the rationale for adopting a composite clinical endpoint for such a trial that includes both liver- and alcohol-related outcomes. We highlight how these concepts were applied to the design of the Integrated Therapies for Alcohol Use in Alcohol-associated Liver Disease (ITAALD) trial.