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

  • STATUS
    Recruiting
  • End date
    Feb 1, 2025
  • participants needed
    7500
  • sponsor
    Herlev Hospital
Updated on 2 May 2022
chest pain
myocardial infarction
infarct
troponin
ischemia
acute myocardial infarction
Accepts healthy volunteers

Summary

Acute myocardial infarction (MI) is defined as a rise and/or fall in cardiac troponins 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 in Danish registries for 12 months after first 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.

Description

The present use of non-sex specific diagnostic cut-off levels of troponins in the diagnosis of acute myocardial infarction (MI) leads to under-diagnostication of acute MI in women and over-diagnostication in men. The purpose of this study is to document this through a randomized nationwide clinical implementation of population and sex-specific cut-off levels.

Coronary artery disease (CAD) is globally the leading cause of mortality for men and women. The latest consensus statement defines myocardial infarction as 1) a rise and/or fall in cardiac troponins with 2) at least one value above the 99th percentile upper reference limit (URL) in the context of 3) symptoms or clinical evidence of myocardial ischemia. Thus, levels of cardiac troponins play a key role in the diagnostic work-up in general. Currently, uniform manufacturer-provided URLs, defined by the 99th percentile of cardiac troponins in a healthy reference population, is applied in Danish hospitals as a diagnostic cut-off for acute MI for both men and women.

Lower levels of cardiac troponins are seen in healthy women as compared to healthy men, i.e. twice as high levels are seen in men. On this basis the clinical use of one uniform 99th percentile URL for cardiac troponins - i.e. applying the same diagnostic levels for men and women - may lead to a systematic under-diagnostication of acute MI in women and potentially an over-diagnostication of acute MI in men. Accordingly, the use of sex-specific 99th percentile URL of cardiac troponins are now recommended in recent guidelines by international cardiological societies, but this remains to be introduced in clinical practice.

The 99th percentile URLs for cardiac troponins currently used in Danish Hospitals are provided by the manufacturer of each specific assay based on blood samples from a healthy reference population collected by the manufacturer. Studies have shown that the 99th percentile value is dependent on patient sex as well as on the reference population selected and the definition for "healthy" used in these studies. It is well known that the 99th percentile URL should stem from a local reference population. This recommendation has never been implemented in Denmark.

The overall purpose of the study is to evaluate the clinical effect of implementing population and sex-specific 99th percentile URL for cardiac troponins in Denmark.

To determine the sex-specific 99th percentile URLs of troponins based on a healthy Danish reference population, blood samples from healthy 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 in Danish registries for 12 months after first admission.

The clinical significance of sex-specific 99th percentile URLs of troponin is poorly investigated and for the same reason not yet implemented in Denmark or many other countries. The basic hypothesis of the DANSPOT study is that the 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. This would be guideline-defining for implementing sex-specific cutoffs for cardiac troponin in Denmark as well as internationally as recommended in guidelines by professional cardiological societies.

Details
Condition Coronary Syndrome, Acute, Coronary Artery Disease, Myocardial Infarction
Treatment Implementation of the new population and sex-specific 99th percentile URL for cardiac troponin
Clinical Study IdentifierNCT05336435
SponsorHerlev Hospital
Last Modified on2 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Suspicion of MI and a measurement of troponin

Exclusion Criteria

Age < 18 years
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note