DANSPOT: A Multicenter Stepped-Wedge Cluster-Randomized Trial of the Reclassification of Acute Myocardial Infarction: Rationale and Study Design

Abstract

Background: Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex-specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex- and Population-Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population- and sex-specific diagnostic thresholds of troponins into clinical practice.

Methods: This study is a nationwide, multicenter, stepped-wedge cluster-randomized trial of the implementation of population- and sex-specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex-specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer-derived thresholds to the new population- and sex-specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex-specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all-cause mortality within 1 year, separately for men and women before and after the implementation of the new sex-specific thresholds.

Conclusions: The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex-specific diagnostic thresholds for troponin based on a national Danish reference population.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.

Keywords: acute coronary syndrome; biomarkers; myocardial infarction; sex factors; troponin.

Figure 1. Study design of the DANSPOT trial, a nationwide implementation of population‐ and sex‐specific diagnostic thresholds of cardiac troponin using a stepped‐wedge design.

With a monthly start interval, each center implements the new population‐ and sex‐specific diagnostic thresholds. After discharge from index admission, patients are followed individually for 12 months. cTn indicates cardiac troponin.

Figure 2. Implementation of population‐ and sex‐specific diagnostic thresholds.

Each center uses the uniform manufacturer‐derived threshold and is randomized to implement the new population‐ and sex‐specific thresholds during the inclusion period. Patients will individually be followed for 12 months after discharge from index admission.

Figure 3. Flowchart for the selection of the primary cohort for analysis. Current uniform threshold and new sex‐specific thresholds are assay‐specific for each center.

ACS indicates acute coronary syndrome; Hs‐cTn, high‐sensitivity cardiac troponin assay; and MI, myocardial infarction.

Figure 4. A health questionnaire was filled out electronically for each participant at registration by a study employee in cooperation with the participant.

Data were stored in the secured web database Research Electronic Data Capture (REDcap).