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.