Supplementary Material for: 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

Background: Patients with acute tachypnea pose diagnostic challenges in the Emergency Department (ED). Biomarkers such as N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) improve diagnostic accuracy and risk stratification in patients with cardiovascular disease but may not be optimally assessed by clinicians in the ED.

Objectives: 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 pre-determined biomarker algorithm improves clinical outcomes in unselected patients hospitalized with tachypnea compared to standard care. The primary outcome is time to mortality or re-hospitalization.

Design: The ACE 4 Study is a single-center, pragmatic, non-pharmacological, randomized clinical trial including patients with acute tachypnea within 24 hours of hospitalization. Patients will be randomized to either early biomarker measurements and feedback in the patient electronic medical health record using a pre-defined biomarker-based algorithm to assess the risk of heart failure (intervention group) or biomarker measurements without structured feedback (control group). We will pre-register 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 pre-determined 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.

Trial registration: ClinicalTrials.Gov: NCT05699564

### 研究背景
急性呼吸急促患者在急诊室（Emergency Department, ED）的诊断存在显著挑战。N末端B型利钠肽原（N-terminal pro-B-type natriuretic peptide, NT-proBNP）、心肌肌钙蛋白T（cardiac troponin T, cTnT）等生物标志物可提升心血管疾病患者的诊断准确性与风险分层能力，但急诊临床医师往往无法对其进行最优评估。

### 研究目标
阿克什心脏检查4（Akershus Cardiac Examination 4, ACE 4）研究的核心目的为：对比标准护理方案，探究针对因呼吸急促住院的未筛选患者，采用预先设定的生物标志物算法、在患者电子健康档案中提供结构化反馈的早期生物标志物检测，是否可改善其临床结局。本研究的主要结局为至死亡或再住院的时间。

### 研究设计
ACE 4研究为单中心、务实型、非药物干预性随机对照试验，纳入住院24小时内出现急性呼吸急促的患者。受试者将被随机分为两组：干预组采用预先设定的基于生物标志物的算法评估心力衰竭风险，并在患者电子健康档案中提供早期生物标志物检测及结构化反馈；对照组仅开展生物标志物检测，不提供结构化反馈。本研究将预先注册研究方案与统计分析计划，并对数据提取及研究执行过程进行监查。

### 研究结论
我们提出如下假说：相较于标准护理方案，采用预先设定的生物标志物算法、在患者电子健康档案中提供结构化反馈的早期生物标志物检测，可改善因呼吸急促住院患者的临床结局。本研究将采用务实型电子健康档案随机对照设计，在日常临床实践中纳入大规模患者群体，对该假说进行验证。

### 试验注册
ClinicalTrials.gov：NCT05699564