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

NCT05336435 | Completed

• 1 other identifier: FSP 20067240
• Study Type: interventional
• Target: 4,865
• Locations: 1 country
• Sites: 22

Brief 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

Keywords

coronary syndrome; myocardial infarction; clinical assessment; biomarker; troponin; myocardial injury

Outcome Measures

Primary Outcomes (1)

• 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 revascularization. All-cause mortality will be ascertained from national patient data extracts. For the diagnosis of type 2 infarctions, we will utilize the criteria established by Saaby et al. Unplanned coronary revascularization 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 revascularization.

  The 12-month period starting from the first troponin measurement during the index admission.

Secondary Outcomes (9)

• All-cause mortality within 12 months

  Within 12 months from the first troponin measurement during the index admission

• Non-fatal myocardial infarction (MI) occurring during any readmission within 12 months

  Within 12 months from the first troponin measurement during the index admission

• Unplanned coronary revascularization (PCI or CABG) performed during any readmission within 12 months

  Within 12 months from the first troponin measurement during the index admission

• Non-fatal myocardial infarction (MI) occurring during the index admission

  During index admission

• Myocardial injury occurring during the index admission

  During index admission

Study Arms (2)

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 utilized 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.

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

Interventions

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

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.

Intervention Arm - New population and sex-specific 99th percentile URLs of troponin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Herlev Hospital: lead
• Rigshospitalet, Denmark: collaborator
• Nordsjaellands Hospital: collaborator
• Amager Hospital: collaborator
• Bispebjerg Hospital: collaborator
• Zealand University Hospital: collaborator
• Slagelse Sygehus: collaborator
• Nykøbing Falster County Hospital: collaborator
• Holbaek Sygehus: collaborator
• Odense University Hospital: collaborator
• Svendborg Hospital: collaborator
• Kolding Sygehus: collaborator
• Aarhus University Hospital: collaborator
• Gødstrup Hospital: collaborator
• Central Jutland Regional Hospital: collaborator
• Randers Regional Hospital: collaborator
• Glostrup University Hospital, Copenhagen: collaborator
• Hvidovre University Hospital: collaborator
• Vejle Hospital: collaborator
• Hospital of Southern Jutland: collaborator
• Horsens Hospital: collaborator
• Aalborg University Hospital: collaborator
• Regionshospital Nordjylland: collaborator
• Sydvestjysk Sygehus: collaborator
• Herlev and Gentofte Hospital: collaborator

Study Sites (22)

Hospital of Southern Jutland

Aabenraa, 6200, Denmark

Location

Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Bispebjerg & Frederiksberg Hospital

Bispebjerg, 2400, Denmark

Location

Rigshospitalet (Blegdamsvej)

Copenhagen Ø, 2100, Denmark

Location

Sydvestjysk Sygehus

Esbjerg, 6700, Denmark

Location

Glostrup University Hospital

Glostrup Municipality, 2600, Denmark

Location

Gødstrup Regional Hospital

Gødstrup, 7400, Denmark

Location

Herlev & Gentofte Hospital

Herlev, 2730, Denmark

Location

C Torp-Pedersen

Hillerød, 3400, Denmark

Location

North Denmark Regional Hospital

Hjørring, 9800, Denmark

Location

Holbaek Sygehus

Holbæk, 4300, Denmark

Location

Horsens Hospital

Horsens, 8700, Denmark

Location

Amager & Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

Sygehus Lillebælt (Kolding Sygehus & Vejle Sygehus)

Kolding, 6000, Denmark

Location

Zealand University Hospital

Køge, 4600, Denmark

Location

Nykøbing Falster County Hospital

Nykøbing Falster, 4800, Denmark

Location

Odense University Hospital

Odense, 5000, Denmark

Location

Randers Regional Hospital

Randers, 8930, Denmark

Location

Slagelse Sygehus

Slagelse, 4200, Denmark

Location

Svendborg Hospital

Svendborg, 5700, Denmark

Location

Central Jutland Regional Hospital (Viborg Hospital & Silkeborg Hospital)

Viborg, 8800, Denmark

Location

Related Publications (2)

• 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.

  PMID: 40513714 DERIVED

• Strandkjaer 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.

  PMID: 38639348 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome; Coronary Artery Disease; Myocardial Infarction; Angina, Unstable

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Kasper K Iversen, MD, DMsc

  Herlev Hospital, University Hospital of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: A readmission diagnosis of acute MI and unplanned coronary revascularization will be adjudicated for all individuals in the primary cohort by an endpoint committee consisting of three cardiologists from another region in Denmark.
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Consultant, DMSc

Model Details: A nationwide cluster-randomized trial with "stepped-wedge" design

Study Record Dates

• First Submitted: March 29, 2022
• First Posted: April 20, 2022
• Study Start: April 1, 2022
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: May 15, 2026

Record last verified: 2026-05

Locations

DK (22)