A Study of Population and Sex-specific Troponin Cutoffs for Ruling Out Acute Myocardial Infarction

Summary

Acute myocardial infarction (MI) is defined as a rise and/or fall in cardiac troponins (cTn) with at least one value above the 99th percentile upper reference limit (URL) in the context of symptoms or clinical evidence of myocardial ischemia. The URL is based on measurements in a healthy reference population. Currently, a sex-uniform manufacturer provided 99th percentile URL of troponin is utilized at Danish hospitals as a diagnostic cutoff for acute MI for both men and women. Reportedly, healthy men have twofold the troponin level compared to healthy women, suggesting that the use of a uniform URL for troponins may lead to the under-diagnostication of acute MI in women and potentially over-diagnostication in men.

The purpose of the DANSPOT study is to evaluate the clinical effect on diagnosis, treatment and outcomes in men and women presenting with acute MI of implementing international guidelines recommendations of sex-specific 99th percentile URLs for troponin into clinical practice.

First, to determine the sex-specific 99th percentile URLs of troponins based on a healthy Danish reference population, blood samples from Danish blood donors, were analyzed using one troponin T assay and four troponin I assays. Second, the DANSPOT study is a nationwide cluster-randomized trial with "stepped-wedge" design with participation of all 22 Danish hospital laboratories and associated departments of cardiology. With one-month intervals, each of 22 centers are randomized to shift from the presently applied uniform 99th percentile URL of troponin to our newly determined population and sex-specific 99th percentiles URLs. Each patient is followed up for 12 months after their first troponin measurement during the index admission.

The hypothesis of the DANSPOT study is that implementation of population and sex-specific 99th URLs for troponin, will ensure that the right patients receive the right treatment. The investigators expect to detect significantly more women with acute MI, theoretically resulting in a more accurate diagnosis and treatment of women and men with acute MI.

Conditions

• Coronary Syndrome, Acute
• Coronary Artery Disease
• Myocardial Infarction

Interventions

DIAGNOSTIC_TEST

Implementation of the new population and sex-specific 99th percentile URL for cardiac troponin

The new population and sex-specific 99th percentiles URLs will be implemented at all Danish hospitals receiving patients with chest pain for initial diagnostics for possible acute MI. This will take place as a randomized step-by-step introduction of population and sex-specific 99th percentile URLs for troponin in all hospital centers with a monthly start time interval. Each center is randomized to shifting from the sex-uniform manufacturer provided 99th percentile URL of cardiac troponin currently used nationwide to the new population and sex-specific 99th percentiles URLs provided by the DANSPOT study's first phase.

Sponsors & Collaborators

• Herlev Hospital

  lead OTHER

• Rigshospitalet, Denmark

  collaborator OTHER

• Nordsjaellands Hospital

  collaborator OTHER

• Amager Hospital

  collaborator OTHER

• Bispebjerg Hospital

  collaborator OTHER

• Zealand University Hospital

  collaborator OTHER

• Slagelse Sygehus

  collaborator OTHER

• Nykøbing Falster County Hospital

  collaborator OTHER

• Holbaek Sygehus

  collaborator OTHER

• Odense University Hospital

  collaborator OTHER

• Svendborg Hospital

  collaborator OTHER

• Kolding Sygehus

  collaborator OTHER

• Aarhus University Hospital

  collaborator OTHER

• Gødstrup Hospital

  collaborator OTHER

• Central Jutland Regional Hospital

  collaborator OTHER

• Randers Regional Hospital

  collaborator OTHER

• Glostrup University Hospital, Copenhagen

  collaborator OTHER

• Hvidovre University Hospital

  collaborator OTHER

• Vejle Hospital

  collaborator OTHER

• Hospital of Southern Jutland

  collaborator OTHER

• Horsens Hospital

  collaborator OTHER

• Aalborg University Hospital

  collaborator OTHER

• Regionshospital Nordjylland

  collaborator OTHER_GOV

• Sydvestjysk Sygehus

  collaborator UNKNOWN

• Herlev and Gentofte Hospital

  collaborator OTHER

Principal Investigators

• Kasper K Iversen, MD, DMsc · Herlev Hospital, University Hospital of Copenhagen

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

SINGLE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-04-01

Primary Completion

2025-02-28

Completion

2025-02-28

Countries

• Denmark

Study Locations