Study Design of the Akershus Cardiac Examination (ACE) 4 Study: Pragmatic Randomized Controlled Trial Assessing the Effect of Early Biomarker Measurements and Structured Feedback in Unselected Patients Hospitalized with Tachypnea

INTRODUCTION: Patients with acute tachypnea pose diagnostic challenges in the emergency department (ED). Biomarkers such as N-terminal pro-B-type natriuretic peptide and cardiac troponin T improve diagnostic accuracy and risk stratification in patients with cardiovascular disease but may not be optimally assessed by clinicians in the ED. The aim of the Akershus Cardiac Examination 4 (ACE 4) study is to test whether early biomarker measurements with structured feedback in patients' electronic health records using a predetermined biomarker algorithm improve clinical outcomes in unselected patients hospitalized with tachypnea compared to standard care. The primary outcome is time to mortality or rehospitalization. METHODS: The ACE 4 study is a single-center, pragmatic, non-pharmacological, randomized clinical trial including patients with acute tachypnea within 24 h of hospitalization. Patients will be randomized to either early biomarker measurements and feedback in the patient electronic medical health record using a predefined biomarker-based algorithm to assess the risk of heart failure (intervention group) or biomarker measurements without structured feedback (control group). We will preregister the study protocol and statistical analysis plan, and we will monitor data extraction and study execution. CONCLUSION: We hypothesize that early biomarker measurements and structured feedback in the patients' electronic health records using a predetermined biomarker algorithm will improve clinical outcomes in patients hospitalized with tachypnea compared to the standard of care. We will test this hypothesis in the ACE 4 study using a pragmatic, electronic health record-randomized controlled design, which enables inclusion of large patient groups in daily clinical practice.