Rationale and Design of ACO-REAL: A Real-World Non-Interventional Study of Acoramidis in Routine Clinical Practice

Introduction Acoramidis, an oral transthyretin stabilizer that achieves near-complete stabilization, is approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) based on the phase 3 study, ATTRibute-CM (NCT03860935). To complement trial data, ACO-REAL (NCT07235462) was designed to generate real-world evidence on acoramidis use in ATTR-CM. This article describes the rationale and design of ACO-REAL.Methods ACO-REAL is an ongoing, prospective, non-interventional, multicenter study planned in approximately 2000 adults with ATTR-CM (wild-type or variant) initiating treatment with acoramidis in real-world settings across 21 European countries. The primary objective of ACO-REAL is to assess the characteristics and treatment patterns of participants with ATTR-CM receiving acoramidis during an observational period of around 12 months.Planned outcomes The primary objective is to assess demographics (including age and sex), disease characteristics, and treatment patterns of participants treated with acoramidis. Disease characteristics include type, diagnosis, and manifestations of ATTR-CM, and ATTR-CM-relevant comorbidities. Treatment patterns include adherence, persistence, and reasons for treatment modifications, including switching from a different ATTR-CM medication to acoramidis. The secondary objective is to describe the safety profile of acoramidis. The clinical course of ATTR-CM in participants initiating acoramidis is also being evaluated through measuring cardiac function, functional capacity and health status (New York Heart Association classification and 6-min walk distance), and health-related quality of life (Kansas City Cardiomyopathy Questionnaire and EuroQol 5-Dimension 5-Level questionnaire). Healthcare resource utilization is also being evaluated. Statistical analyses will be exploratory and descriptive. Categorical variables will be presented as frequencies and continuous variables as sample statistics.Conclusions ACO-REAL is the first multinational observational study to collect regular, prospective, real-world data in participants with ATTR-CM treated with acoramidis. This study aims to provide insights into ATTR-CM treatment using real-world evidence from European healthcare systems and may help to guide decision-making in clinical practice. Graphical abstract available for this article.Trial registration ClinicalTrials.gov identifier, NCT07235462.