Coronary Syndrome, AcuteDANSPOTNCT05336435
A Study of Population and Sex-specific Troponin Cutoffs for Ruling Out Acute Myocardial Infarction
A study testing Implementation of the new population and sex-specific 99th percentile URL for cardiac troponin in people with Coronary Syndrome, Acute and Coronary Artery Disease, run by Herlev Hospital at 22 sites in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Coronary Syndrome, Acute, Coronary Artery Disease, Myocardial Infarction
- What is being tested?
- Implementation of the new population and sex-specific 99th percentile URL for cardiac troponin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5,175 participants
- Where
- 22 sitesDenmark
- Study dates
- 1 Apr 2022to 28 Feb 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- The primary cohort will include the women and men who are expected to be most significantly impacted by the intervention, and this group is specifically defined by
- Presenting complaints suggestive of ACS
- At least one cTn measurement within 24 hours of admission
- A peak cTn value between the current sex-uniform manufacturer-derived 99th percentile URL and the novel sex-and population-specific 99th percentile URLs for women and men.
- Presenting complaints suggestive of ACS will be identified in hospital records by the following presenting complaints of "chest pain" (DR074), "angina pectoris" (DI20), "observation due to suspicion of myocardial infarction" (Z034), "myocardial infarction" (DI21), "abdominal and pelvic pain" (DR10), "pain in the throat and chest" (DR07), "dyspnea" (DR060), "reflux" (DK21), "ischemic heart disease" (DI22-DI25) and "observation due to suspicion of another cardiovascular disorder" (DZ035).
- Study participants are included at their index admission, and subsequent admissions are evaluated in follow up analyses.
Who cannot join
- Age < 18 years
- Patients with discharge diagnoses with conditions like pericarditis, myocarditis, endocarditis, cardiomyopathy, valve disease, arrhythmia, heart failure, pulmonary embolism, respiratory diseases, infectious diseases, digestive system diseases excluding reflux, digestive system diseases, diseases of the urinary and reproductive organs, and diseases of bones, muscles, and connective tissue, and do not have a discharge diagnosis of myocardial infarction or angina pectoris
- The initial month following the implementation of the new sex-specific 99th percentile URLs will be excluded from consideration, as it will be seen as an adjustment period. Consequently, the intervention period will be extended by one month.
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
Denmark22 sites
Hospital of Southern Jutland
Aabenraa, 6200
Aalborg University Hospital
Aalborg, 9000
Aarhus University Hospital
Aarhus, 8000
Bispebjerg & Frederiksberg Hospital
Bispebjerg, 2400
Rigshospitalet (Blegdamsvej)
Copenhagen Ø, 2100
Sydvestjysk Sygehus
Esbjerg, 6700
Glostrup University Hospital
Glostrup Municipality, 2600
Gødstrup Regional Hospital
Gødstrup, 7400
Herlev & Gentofte Hospital
Herlev, 2730
C Torp-Pedersen
Hillerød, 3400
North Denmark Regional Hospital
Hjørring, 9800
Holbaek Sygehus
Holbæk, 4300
Horsens Hospital
Horsens, 8700
Amager & Hvidovre Hospital
Hvidovre, 2650
Zealand University Hospital
Køge, 4600
Sygehus Lillebælt (Kolding Sygehus & Vejle Sygehus)
Kolding, 6000
Nykøbing Falster County Hospital
Nykøbing Falster, 4800
Odense University Hospital
Odense, 5000
Randers Regional Hospital
Randers, 8930
Slagelse Sygehus
Slagelse, 4200
Svendborg Hospital
Svendborg, 5700
Central Jutland Regional Hospital (Viborg Hospital & Silkeborg Hospital)
Viborg, 8800
About this study
Official title: A Randomised Clinical Trial (RCT) of Population- and Sex-specific Troponin Cutoffs for Ruling Out Acute Myocardial Infarction - The Danish Study of Population and Sex-Specific Cutoffs of Troponin
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 utilised 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.
Read more
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 analysed using one troponin T assay and four troponin I assays. Second, the DANSPOT study is a nationwide cluster-randomised trial with a "stepped-wedge" design, with participation of all 22 Danish hospital laboratories and associated departments of cardiology. With one-month intervals, each of the 22 centres is randomised to shift from the presently applied uniform 99th percentile URL of troponin to our newly determined population- and sex-specific 99th percentile URL. 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 percentile 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.
Read the detailed description
The present use of non-sex-specific diagnostic cut-off levels of troponins in the diagnosis of acute myocardial infarction (MI) leads to underdiagnosis of acute MI in women and overdiagnosis in men. The purpose of this study is to document this through a randomised 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, are 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 compared with healthy men; i.e., levels are twice as high 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 URLs of cardiac troponins is 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 depends on patient sex, the reference population selected, and the definition of "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 URLs 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 analysed using one troponin T assay and four troponin I assays. Second, the DANSPOT study is a nationwide cluster-randomised trial with a "stepped-wedge" design, with participation of all 22 Danish hospital laboratories and associated departments of cardiology. With one-month intervals, each of the 22 centres is randomised to shift from the presently applied uniform 99th percentile URL of troponin to our newly determined population- and sex-specific 99th percentile URL. Each patient is followed up for 12 months after their first troponin measurement during the index admission.
The clinical significance of sex-specific 99th percentile URLs for troponin remains 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 implementing population- and sex-specific 99th percentile 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 and internationally, as recommended by professional cardiological societies.
- Being tested
- Implementation of the new population and sex-specific 99th percentile URL for cardiac troponin
- Keywords
- coronary syndrome, myocardial infarction, clinical assessment, biomarker, troponin, myocardial injury
- Medical subject headings
- Acute Coronary Syndrome, Coronary Artery Disease, Myocardial Infarction, Angina, Unstable
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Implementation of the new population and sex-specific 99th percentile URL for cardiac troponinDiagnostic test
The new population and sex-specific 99th percentile 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 randomised, step-by-step introduction of population- and sex-specific 99th percentile URLs for troponin in all hospital centres, with a monthly start time interval. Each centre is randomised to shift from the sex-uniform manufacturer-provided 99th percentile URL of cardiac troponin currently used nationwide to the new population- and sex-specific 99th percentile URLs provided by the DANSPOT study's first phase.
| Study group | Role | What they receive |
|---|---|---|
| Control Arm - Current sex-uniform manufacturer provided 99th percentile URL of troponin | No intervention | Standard use of the current sex-uniform manufacturer-provided 99th percentile URL of troponin is utilised at Danish hospitals as a diagnostic cutoff for acute MI for both men and women |
| Intervention Arm - New population and sex-specific 99th percentile URLs of troponin | Active comparator | Implementation of the new population and sex-specific 99th percentile URLs of troponin for the specific assay utilized at the enrolled centers. Receives: Diagnostic Test: Implementation of the new population and sex-specific 99th percentile URL for cardiac troponin |
What is being measured
The primary outcome is the main question the study is designed to answer.
A composite endpoint of: 1) readmission for myocardial infarction 2) readmission for unplanned revascularisation (PCI or CABG) 3) all cause mortality All events must occur within 12 months of the first troponin measurement during the index admission
We will compare the occurrence of the primary outcome separately in men and women within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. For individuals included in the primary cohort, all readmissions within the 12-month follow-up period will be adjudicated by an endpoint committee to identify type 1, type 2, and type 4b myocardial infarction, as well as unplanned coronary revascularisation. All-cause mortality will be ascertained from national patient data extracts. For the diagnosis of type 2 infarctions, we will utilise the criteria established by Saaby et al. Unplanned coronary revascularisation is defined as any percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) performed after discharge from the index admission, in patients without coronary angiography or cardiac CT performed or planned during the index admission, leading to planned revascularisation.
Measured: The 12-month period starting from the first troponin measurement during the index admission.
Secondary outcomes (11)
All-cause mortality within 12 months
Secondary endpoints will be evaluated separately in women and men within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. All-cause mortality within follow-up will be identified through patient data extracts. Follow-up is defined as the 12-month period starting from the first troponin measurement during the index admission.
Measured: Within 12 months from the first troponin measurement during the index admission
Non-fatal myocardial infarction (MI) occurring during any readmission within 12 months
Secondary endpoints will be evaluated separately in women and men within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. Non-fatal MI during readmissions within follow-up will be identified through endpoint adjudication. Follow-up is defined as the 12-month period starting from the first troponin measurement during the index admission.
Measured: Within 12 months from the first troponin measurement during the index admission
Unplanned coronary revascularisation (PCI or CABG) performed during any readmission within 12 months
Secondary endpoints will be evaluated separately in women and men within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. Unplanned coronary revascularisation during readmissions within follow-up will be identified through endpoint adjudication. Follow-up is defined as the 12-month period starting from the first troponin measurement during the index admission.
Measured: Within 12 months from the first troponin measurement during the index admission
Non-fatal myocardial infarction (MI) occurring during the index admission
Secondary endpoints will be evaluated separately in women and men within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. Non-fatal MI during the index admission will be identified through patient data extracts.
Measured: During index admission
Myocardial injury occurring during any readmission within 12 months
Secondary endpoints will be evaluated separately in women and men within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. Myocardial injury during readmissions within follow-up will be identified through endpoint adjudication. Follow-up is defined as the 12-month period starting from the first troponin measurement during the index admission.
Measured: Within 12 months from the first troponin measurement during the index admission
Myocardial injury occurring during the index admission
Secondary endpoints will be evaluated separately in women and men within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. Myocardial injury during the index admission will be identified through patient data extracts.
Measured: During index admission
Coronary angiography or coronary computed tomography performed during the index admission
Secondary endpoints will be evaluated separately in women and men within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. Coronary angiography and coronary computed tomography performed during the index admission will be identified through patient data extracts.
Measured: During index admission
Documented initiation or continuation of guideline-directed medical therapy for myocardial infarction during the index admission
Secondary endpoints will be evaluated separately in women and men within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. Guideline-directed medical therapy during the index admission will be identified through patient data extracts and verified in the medical records for the indication of myocardial infarction. Guideline-directed medical therapy is defined as treatment with acetylsalicylic acid, a P2Y12 inhibitor, and statin therapy, or appropriate alternative therapy when standard treatment is contraindicated, not tolerated, or clinically inappropriate. Treatment classification will be based on the documented clinical indication and treatment intention.
Measured: During the index admission
Coronary revascularisation (PCI or CABG) performed during the index admission or planned during the index admission and subsequently performed within 3 months
Secondary endpoints will be evaluated separately in women and men within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. Coronary revascularisation performed during the index admission, or planned during the index admission and subsequently performed within 3 months, will be identified using patient data extracts.
Measured: During the index admission or within 3 months of discharge
Coronary angiography or coronary computed tomography performed during the index admission without subsequent planned coronary revascularisation within 3 months
Secondary endpoints will be evaluated separately in women and men within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. Coronary angiography and coronary computed tomography performed during the index admission without subsequent planned coronary revascularisation within 3 months will be identified through patient data extracts.
Measured: During the index admission or within 3 months of discharge
Length of stay during the index admission in the primary cohort
Secondary endpoints will be evaluated separately in women and men within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. The length of stay during the index admission will be identified through patient data extracts.
Measured: During index admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2022
- Study start1 Apr 2022
- Primary completion28 Feb 2025
- Study completion28 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Coronary Syndrome, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- A nationwide cluster-randomised trial with "stepped-wedge" design
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 5,175 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herlev Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Nordsjaellands Hospital, Amager Hospital, Bispebjerg Hospital, Zealand University Hospital, Slagelse Sygehus, Nykøbing Falster County Hospital, Holbaek Sygehus, Odense University Hospital, Svendborg Hospital, Kolding Sygehus, Aarhus University Hospital, Gødstrup Hospital, Central Jutland Regional Hospital, Randers Regional Hospital, Glostrup University Hospital, Copenhagen, Hvidovre University Hospital, Vejle Hospital, Hospital of Southern Jutland, Horsens Hospital, Aalborg University Hospital, Regionshospital Nordjylland, Sydvestjysk Sygehus, Herlev and Gentofte Hospital
- Responsible party
- Principal investigator, Kasper Iversen, Herlev Hospital
- Investigators
- Kasper K Iversen, MD, DMsc, Principal investigator, Herlev Hospital, University Hospital of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05336435
- Sponsor's protocol ID
- FSP 20067240
- Acronym
- DANSPOT
- Status last verified
- Aug 2026
- First submitted
- 29 Mar 2022
- Last updated
- 26 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Hasselbalch RB, Strandkjaer N, Kristensen J, Jorgensen N, Kock TO, Lange T, Ostrowski SR, Nissen J, Larsen MH, Vesterager Pedersen OB, Bor MV, Afzal S, Kamstrup PR, Dahl M, Hilsted L, Rode L, Jorgensen NR, Torp-Pedersen C, Bundgaard H, Iversen KK. Impact of age on cardiac troponin concentration among healthy individuals. Clin Biochem. 2025 Aug;138:110956. doi: 10.1016/j.clinbiochem.2025.110956. Epub 2025 Jun 11.
PubMed 40513714Strandkjaer N, Jorgensen N, Hasselbalch RB, Kristensen J, Knudsen MSS, Kock TO, Lange T, Lindholm MG, Bruun NE, Holmvang L, Terkelsen CJ, Pedersen CK, Christensen MK, Lassen JF, Hilsted L, Ladefoged S, Nybo M, Bor MV, Dahl M, Hansen AB, Kamstrup PR, Bundgaard H, Torp-Pedersen C, Iversen KK. DANSPOT: A Multicenter Stepped-Wedge Cluster-Randomized Trial of the Reclassification of Acute Myocardial Infarction: Rationale and Study Design. J Am Heart Assoc. 2024 May 7;13(9):e033493. doi: 10.1161/JAHA.123.033493. Epub 2024 Apr 19.
PubMed 38639348
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Clinical Trial (RCT) of Population- and Sex-specific Troponin Cutoffs for Ruling Out Acute Myocardial Infarction - The Danish Study of Population and Sex-Specific Cutoffs of Troponin
- ClinicalTrials.gov ID
- NCT05336435
- Acronym / sponsor ID
- DANSPOT / FSP 20067240
- Keywords
- coronary syndrome, myocardial infarction, clinical assessment, biomarker, troponin, myocardial injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5,175 participants (actual)
- Lead sponsor
- Herlev HospitalUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Nordsjaellands Hospital, Amager Hospital, Bispebjerg Hospital, Zealand University Hospital, Slagelse Sygehus, Nykøbing Falster County Hospital, Holbaek Sygehus, Odense University Hospital, Svendborg Hospital, Kolding Sygehus, Aarhus University Hospital, Gødstrup Hospital, Central Jutland Regional Hospital, Randers Regional Hospital, Glostrup University Hospital, Copenhagen, Hvidovre University Hospital, Vejle Hospital, Hospital of Southern Jutland, Horsens Hospital, Aalborg University Hospital, Regionshospital Nordjylland, Sydvestjysk Sygehus, Herlev and Gentofte Hospital
- Study start
- 1 Apr 2022 (actual)
- Primary completion
- 28 Feb 2025 (actual)
- Study completion
- 28 Feb 2025 (actual)
- First posted
- 20 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 utilised 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 analysed using one troponin T assay and four troponin I assays. Second, the DANSPOT study is a nationwide cluster-randomised trial with a "stepped-wedge" design, with participation of all 22 Danish hospital laboratories and associated departments of cardiology. With one-month intervals, each of the 22 centres is randomised to shift from the presently applied uniform 99th percentile URL of troponin to our newly determined population- and sex-specific 99th percentile URL. 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 percentile 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.
Detailed description
The present use of non-sex-specific diagnostic cut-off levels of troponins in the diagnosis of acute myocardial infarction (MI) leads to underdiagnosis of acute MI in women and overdiagnosis in men. The purpose of this study is to document this through a randomised 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, are 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 compared with healthy men; i.e., levels are twice as high 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 URLs of cardiac troponins is 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 depends on patient sex, the reference population selected, and the definition of "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 URLs 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 analysed using one troponin T assay and four troponin I assays. Second, the DANSPOT study is a nationwide cluster-randomised trial with a "stepped-wedge" design, with participation of all 22 Danish hospital laboratories and associated departments of cardiology. With one-month intervals, each of the 22 centres is randomised to shift from the presently applied uniform 99th percentile URL of troponin to our newly determined population- and sex-specific 99th percentile URL. Each patient is followed up for 12 months after their first troponin measurement during the index admission.
The clinical significance of sex-specific 99th percentile URLs for troponin remains 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 implementing population- and sex-specific 99th percentile 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 and internationally, as recommended by professional cardiological societies.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- A nationwide cluster-randomised trial with "stepped-wedge" design
| Arm | Type | Receives |
|---|---|---|
| Control Arm - Current sex-uniform manufacturer provided 99th percentile URL of troponin | No intervention | –Standard use of the current sex-uniform manufacturer-provided 99th percentile URL of troponin is utilised at Danish hospitals as a diagnostic cutoff for acute MI for both men and women |
| Intervention Arm - New population and sex-specific 99th percentile URLs of troponin | Active comparator | Diagnostic Test: Implementation of the new population and sex-specific 99th percentile URL for cardiac troponinImplementation of the new population and sex-specific 99th percentile URLs of troponin for the specific assay utilized at the enrolled centers. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- The primary cohort will include the women and men who are expected to be most significantly impacted by the intervention, and this group is specifically defined by
- Presenting complaints suggestive of ACS
- At least one cTn measurement within 24 hours of admission
- A peak cTn value between the current sex-uniform manufacturer-derived 99th percentile URL and the novel sex-and population-specific 99th percentile URLs for women and men.
- Presenting complaints suggestive of ACS will be identified in hospital records by the following presenting complaints of "chest pain" (DR074), "angina pectoris" (DI20), "observation due to suspicion of myocardial infarction" (Z034), "myocardial infarction" (DI21), "abdominal and pelvic pain" (DR10), "pain in the throat and chest" (DR07), "dyspnea" (DR060), "reflux" (DK21), "ischemic heart disease" (DI22-DI25) and "observation due to suspicion of another cardiovascular disorder" (DZ035).
Key exclusion criteria (3 listed)
- Age < 18 years
- Patients with discharge diagnoses with conditions like pericarditis, myocarditis, endocarditis, cardiomyopathy, valve disease, arrhythmia, heart failure, pulmonary embolism, respiratory diseases, infectious diseases, digestive system diseases excluding reflux, digestive system diseases, diseases of the urinary and reproductive organs, and diseases of bones, muscles, and connective tissue, and do not have a discharge diagnosis of myocardial infarction or angina pectoris
- The initial month following the implementation of the new sex-specific 99th percentile URLs will be excluded from consideration, as it will be seen as an adjustment period. Consequently, the intervention period will be extended by one month.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Implementation of the new population and sex-specific 99th percentile URL for cardiac troponinThe new population and sex-specific 99th percentile 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 randomised, step-by-step introduction of population- and sex-specific 99th percentile URLs for troponin in all hospital centres, with a monthly start time interval. Each centre is randomised to shift from the sex-uniform manufacturer-provided 99th percentile URL of cardiac troponin currently used nationwide to the new population- and sex-specific 99th percentile URLs provided by the DANSPOT study's first phase. | Diagnostic test | Intervention Arm - New population and sex-specific 99th percentile URLs of troponin |
Primary outcome
A composite endpoint of: 1) readmission for myocardial infarction 2) readmission for unplanned revascularisation (PCI or CABG) 3) all cause mortality All events must occur within 12 months of the first troponin measurement during the index admission
Time frame: The 12-month period starting from the first troponin measurement during the index admission.
We will compare the occurrence of the primary outcome separately in men and women within the primary cohort before and after implementation of the new sex-specific diagnostic thresholds. For individuals included in the primary cohort, all readmissions within the 12-month follow-up period will be adjudicated by an endpoint committee to identify type 1, type 2, and type 4b myocardial infarction, as well as unplanned coronary revascularisation. All-cause mortality will be ascertained from national patient data extracts. For the diagnosis of type 2 infarctions, we will utilise the criteria established by Saaby et al. Unplanned coronary revascularisation is defined as any percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) performed after discharge from the index admission, in patients without coronary angiography or cardiac CT performed or planned during the index admission, leading to planned revascularisation.
11 secondary outcomes
All-cause mortality within 12 months
Time frame: Within 12 months from the first troponin measurement during the index admission
Non-fatal myocardial infarction (MI) occurring during any readmission within 12 months
Time frame: Within 12 months from the first troponin measurement during the index admission
Unplanned coronary revascularisation (PCI or CABG) performed during any readmission within 12 months
Time frame: Within 12 months from the first troponin measurement during the index admission
Non-fatal myocardial infarction (MI) occurring during the index admission
Time frame: During index admission
Myocardial injury occurring during any readmission within 12 months
Time frame: Within 12 months from the first troponin measurement during the index admission
Myocardial injury occurring during the index admission
Time frame: During index admission
Coronary angiography or coronary computed tomography performed during the index admission
Time frame: During index admission
Documented initiation or continuation of guideline-directed medical therapy for myocardial infarction during the index admission
Time frame: During the index admission
Coronary revascularisation (PCI or CABG) performed during the index admission or planned during the index admission and subsequently performed within 3 months
Time frame: During the index admission or within 3 months of discharge
Coronary angiography or coronary computed tomography performed during the index admission without subsequent planned coronary revascularisation within 3 months
Time frame: During the index admission or within 3 months of discharge
Length of stay during the index admission in the primary cohort
Time frame: During index admission
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2026.
- Derived from this study: PubMed 40513714Hasselbalch RB, Strandkjaer N, Kristensen J, Jorgensen N, Kock TO, Lange T, Ostrowski SR, Nissen J, Larsen MH, Vesterager Pedersen OB, Bor MV, Afzal S, Kamstrup PR, Dahl M, Hilsted L, Rode L, Jorgensen NR, Torp-Pedersen C, Bundgaard H, Iversen KK. Impact of age on cardiac troponin concentration among healthy individuals. Clin Biochem. 2025 Aug;138:110956. doi: 10.1016/j.clinbiochem.2025.110956. Epub 2025 Jun 11.
- Derived from this study: PubMed 38639348Strandkjaer N, Jorgensen N, Hasselbalch RB, Kristensen J, Knudsen MSS, Kock TO, Lange T, Lindholm MG, Bruun NE, Holmvang L, Terkelsen CJ, Pedersen CK, Christensen MK, Lassen JF, Hilsted L, Ladefoged S, Nybo M, Bor MV, Dahl M, Hansen AB, Kamstrup PR, Bundgaard H, Torp-Pedersen C, Iversen KK. DANSPOT: A Multicenter Stepped-Wedge Cluster-Randomized Trial of the Reclassification of Acute Myocardial Infarction: Rationale and Study Design. J Am Heart Assoc. 2024 May 7;13(9):e033493. doi: 10.1161/JAHA.123.033493. Epub 2024 Apr 19.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kasper K Iversen, MD, DMsc principal investigator
Herlev Hospital, University Hospital of Copenhagen
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Implementation of the new population and sex-specific 99th percentile URL for cardiac troponin in people with Coronary Syndrome, Acute and Coronary Artery Disease, run by Herlev Hospital at 22 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A composite endpoint of: 1) readmission for myocardial infarction 2) readmission for unplanned revascularisation (PCI or CABG) 3) all cause mortality All events must occur within 12 months of the first troponin measurement during the index admission (time frame: The 12-month period starting from the first troponin measurement during the index admission.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05336435, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.