Myocardial InfarctionCODE-MINCT03819894
Hs-cTn - Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women
A study testing Introduction of a lower female hs-cTn threshold in people with Myocardial Infarction and Sex Differences, run by BC Centre for Improved Cardiovascular Health at 1 site in Canada.
Trial summary
The project is focussed on evaluating the impact of using a female-specific threshold in the diagnosis of myocardial infarction. This female threshold is lower than the overall hs-cTn threshold currently in use. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Myocardial Infarction, Sex Differences, High Sensitivity Troponin
- What is being tested?
- Introduction of a lower female hs-cTn threshold
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24,000 participants
- Where
- 1 siteCanada
- Study dates
- 8 Feb 2020to 31 Mar 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >20 years of age
- Present to the ED with chest pain or shortness of breath suggestive of ischemia
- Have a valid personal health identifier
- Have 1 hs-cTn test result
Who cannot join
- Have ST elevation myocardial infarction (STEMI)
- Not residents in the same province as the hospital ED to which they present or move out of province within a year
Trial locations and contacts
1 site in 1 country.
About this study
The project is focussed on evaluating the impact of using a female-specific threshold in the diagnosis of myocardial infarction. This female threshold is lower than the overall hs-cTn threshold currently in use. The investigators hypothesize that this change in process, applied at the hospital level, will lead to better assessment, treatment and outcomes of women presenting to the emergency department with chest pain that is cardiac in nature.
Read the detailed description
In subjects with suspected acute coronary syndromes (ACS), females are significantly less likely to undergo investigations, receive evidence-based treatments, and consistently have worse outcomes than males. The gap in outcomes is particularly marked among adults < 55 years of age. Sex differences in symptom presentation and in the diagnostic threshold for cardiac biomarkers have been suggested as reasons for the under-diagnosis and under-treatment of women. Cardiac troponin (cTn) T and I are proteins specific to the myocardium, which with elevated and changing concentrations detected in the blood, along with signs or symptoms consistent with myocardial ischemia, are indicative of a diagnosis of myocardial infarction (MI). With the introduction of high-sensitivity (hs) cTn tests, which allow the detection of very low concentrations of troponin, it has become evident that the level of cTn in a healthy population is approximately two-fold higher in males than in females.
Consequently, the 99th percentile threshold for cTn, the reference value used in diagnosis of MI, is lower in females compared to males. Despite this evidence and recent guidelines recommending the use of sex specific thresholds, a single, overall cTn threshold is still being used for diagnosis of MI, in both men and women, in most clinical settings.
There is mounting evidence from several jurisdictions that the rate of MI is increasing among younger females, and that there is a persistent under-diagnosis, under-treatment, and high risk of adverse outcomes among females, especially younger females, compared to their male counterparts. A better approach to the diagnostic assessment of females presenting to the emergency department (ED) with chest pain is therefore urgently needed. Additionally, several Canadian hospitals have recently made the transition from sensitive to high sensitivity cTn assays, allowing for the examination of subtle but important sex-specific differences in cTn concentrations. With this background, the investigators propose a nationwide, randomized clinical trial (RCT) to determine whether establishing female thresholds results in improved diagnosis and treatment of MI and therefore improved prognosis in women.
To determine whether the use of female hs-cTn thresholds in the assessment of women presenting to the ED with chest pain suggestive of cardiac ischemia, improves diagnostic assessment, treatment and 2-year outcomes. Specifically, the investigators will examine the impact of using female hs-cTn thresholds on:
- Diagnostic and therapeutic strategies;
- Prognosis: 2-year all-cause mortality, non-fatal MI, incident heart failure (HF) hospitalization or emergent/urgent coronary revascularization;
- Costs of diagnostic testing and treatment.
- Being tested
- Introduction of a lower female hs-cTn threshold
- Keywords
- myocardial infarction, sex differences, high-sensitivity cardiac troponin, biomarkers, heart attack, emergency department, acute coronary syndrome
- Medical subject headings
- Myocardial Infarction, Emergencies, Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Introduction of a lower female hs-cTn thresholdDiagnostic test
The new female hs-cTn threshold will be baed on current recommendations for each of the assays used (hs-cTn T and I). The hospitals are the unit of randomization. At 5-month intervals, randomly selected hospitals will be advised that they are to transition to the intervention phase. For all men, the standard of care, overall population threshold will be used throughout the entire study.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | The intervention is the introduction of a lower female threshold. In cluster-randomized trials, the cluster (i.e., hospital) is the unit of randomization. Receives: Diagnostic Test: Introduction of a lower female hs-cTn threshold |
| Control | No intervention | The control phase will be standard of care, with the use of an overall population hs-cTn T and I threshold, for both men and women, to identify those with myocardial injury/infarction. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with all-cause mortality, non-fatal myocardial infarction, hospitalization for incident heart failure, or urgent/emergent coronary revascularization (percutaneous coronary intervention or coronary artery bypass surgery)
Composite of all-cause mortality, re-admission for non-fatal MI, incident HF, or urgent/emergent coronary revascularization
Measured: 2-year post index emergency department presentation
Secondary outcomes (3)
Number of patients with a) Non-fatal myocardial infarction or all-cause mortality; b) Urgent/emergent coronary revascularization or all-cause mortality; c) Hospitalization for heart failure or all-cause mortality.
The secondary outcomes include the individual components of the composite outcome with death, to account for competing risk.
Measured: 2-year post index emergency department presentation
Proportion of patients who fill at least one prescription for evidence-based cardiac medications
Medications include beta-blockers, Angiotensin Converting Enzyme (ACE)-I/Angiotensin II receptor blockers (ARB), statins, anti-platelets
Measured: Within 90 days of ED visit
Proportion of patients who undergo diagnostic tests
Diagnostic tests include nuclear medicine cardiac scan, exercise stress test, diagnostic cardiac catheterization/CT angiogram or echocardiogram
Measured: Within 90 days of ED visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2019
- Study start8 Feb 2020
- Primary completion31 Mar 2025 (estimated)
- Study completion31 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myocardial InfarctionStudies 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
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Stepped-wedge cluster-randomized trial. Unidirectional crossover design where clusters cross over sequentially, in random order, from the control to intervention phase.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 24,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BC Centre for Improved Cardiovascular Health
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Karin Humphries, DSc, Principal investigator, Medicine, Cardiology, UBC, BC Centre for Improved Cardiovascular Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03819894
- Sponsor's protocol ID
- H18-02116
- Acronym
- CODE-MI
- Status last verified
- Oct 2024
- First submitted
- 21 Jan 2019
- Last updated
- 9 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Zhao Y, Izadnegahdar M, Lee MK, Kavsak PA, Singer J, Scheuermeyer F, Udell JA, Robinson S, Norris CM, Lyon AW, Pilote L, Cox J, Hassan A, Rychtera A, Johnson D, Mills NL, Christenson J, Humphries KH. High-Sensitivity Cardiac Troponin-Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women (CODE-MI): Rationale and design for a multicenter, stepped-wedge, cluster-randomized trial. Am Heart J. 2020 Nov;229:18-28. doi: 10.1016/j.ahj.2020.06.013. Epub 2020 Jun 25.
PubMed 32916606
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hs-cTn - Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women
- ClinicalTrials.gov ID
- NCT03819894
- Acronym / sponsor ID
- CODE-MI / H18-02116
- Keywords
- myocardial infarction, sex differences, high-sensitivity cardiac troponin, biomarkers, heart attack, emergency department, acute coronary syndrome
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24,000 participants (estimated)
- Lead sponsor
- BC Centre for Improved Cardiovascular HealthUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- 8 Feb 2020 (actual)
- Primary completion
- 31 Mar 2025 (estimated)
- Study completion
- 31 Mar 2025 (estimated)
- First posted
- 29 Jan 2019 (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.
The project is focussed on evaluating the impact of using a female-specific threshold in the diagnosis of myocardial infarction. This female threshold is lower than the overall hs-cTn threshold currently in use. The investigators hypothesize that this change in process, applied at the hospital level, will lead to better assessment, treatment and outcomes of women presenting to the emergency department with chest pain that is cardiac in nature.
Detailed description
In subjects with suspected acute coronary syndromes (ACS), females are significantly less likely to undergo investigations, receive evidence-based treatments, and consistently have worse outcomes than males. The gap in outcomes is particularly marked among adults < 55 years of age. Sex differences in symptom presentation and in the diagnostic threshold for cardiac biomarkers have been suggested as reasons for the under-diagnosis and under-treatment of women. Cardiac troponin (cTn) T and I are proteins specific to the myocardium, which with elevated and changing concentrations detected in the blood, along with signs or symptoms consistent with myocardial ischemia, are indicative of a diagnosis of myocardial infarction (MI). With the introduction of high-sensitivity (hs) cTn tests, which allow the detection of very low concentrations of troponin, it has become evident that the level of cTn in a healthy population is approximately two-fold higher in males than in females.
Consequently, the 99th percentile threshold for cTn, the reference value used in diagnosis of MI, is lower in females compared to males. Despite this evidence and recent guidelines recommending the use of sex specific thresholds, a single, overall cTn threshold is still being used for diagnosis of MI, in both men and women, in most clinical settings.
There is mounting evidence from several jurisdictions that the rate of MI is increasing among younger females, and that there is a persistent under-diagnosis, under-treatment, and high risk of adverse outcomes among females, especially younger females, compared to their male counterparts. A better approach to the diagnostic assessment of females presenting to the emergency department (ED) with chest pain is therefore urgently needed. Additionally, several Canadian hospitals have recently made the transition from sensitive to high sensitivity cTn assays, allowing for the examination of subtle but important sex-specific differences in cTn concentrations. With this background, the investigators propose a nationwide, randomized clinical trial (RCT) to determine whether establishing female thresholds results in improved diagnosis and treatment of MI and therefore improved prognosis in women.
To determine whether the use of female hs-cTn thresholds in the assessment of women presenting to the ED with chest pain suggestive of cardiac ischemia, improves diagnostic assessment, treatment and 2-year outcomes. Specifically, the investigators will examine the impact of using female hs-cTn thresholds on:
- Diagnostic and therapeutic strategies;
- Prognosis: 2-year all-cause mortality, non-fatal MI, incident heart failure (HF) hospitalization or emergent/urgent coronary revascularization;
- Costs of diagnostic testing and treatment.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Stepped-wedge cluster-randomized trial. Unidirectional crossover design where clusters cross over sequentially, in random order, from the control to intervention phase.
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Diagnostic Test: Introduction of a lower female hs-cTn thresholdThe intervention is the introduction of a lower female threshold. In cluster-randomized trials, the cluster (i.e., hospital) is the unit of randomization. |
| Control | No intervention | –The control phase will be standard of care, with the use of an overall population hs-cTn T and I threshold, for both men and women, to identify those with myocardial injury/infarction. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- >20 years of age
- Present to the ED with chest pain or shortness of breath suggestive of ischemia
- Have a valid personal health identifier
- Have 1 hs-cTn test result
Key exclusion criteria (2 listed)
- Have ST elevation myocardial infarction (STEMI)
- Not residents in the same province as the hospital ED to which they present or move out of province within a year
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 |
|---|---|---|
| Introduction of a lower female hs-cTn thresholdThe new female hs-cTn threshold will be baed on current recommendations for each of the assays used (hs-cTn T and I). The hospitals are the unit of randomization. At 5-month intervals, randomly selected hospitals will be advised that they are to transition to the intervention phase. For all men, the standard of care, overall population threshold will be used throughout the entire study. | Diagnostic test | Intervention |
Primary outcome
Number of patients with all-cause mortality, non-fatal myocardial infarction, hospitalization for incident heart failure, or urgent/emergent coronary revascularization (percutaneous coronary intervention or coronary artery bypass surgery)
Time frame: 2-year post index emergency department presentation
Composite of all-cause mortality, re-admission for non-fatal MI, incident HF, or urgent/emergent coronary revascularization
3 secondary outcomes
Number of patients with a) Non-fatal myocardial infarction or all-cause mortality; b) Urgent/emergent coronary revascularization or all-cause mortality; c) Hospitalization for heart failure or all-cause mortality.
Time frame: 2-year post index emergency department presentation
Proportion of patients who fill at least one prescription for evidence-based cardiac medications
Time frame: Within 90 days of ED visit
Proportion of patients who undergo diagnostic tests
Time frame: Within 90 days of ED visit
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2024.
- Derived from this study: PubMed 32916606Zhao Y, Izadnegahdar M, Lee MK, Kavsak PA, Singer J, Scheuermeyer F, Udell JA, Robinson S, Norris CM, Lyon AW, Pilote L, Cox J, Hassan A, Rychtera A, Johnson D, Mills NL, Christenson J, Humphries KH. High-Sensitivity Cardiac Troponin-Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women (CODE-MI): Rationale and design for a multicenter, stepped-wedge, cluster-randomized trial. Am Heart J. 2020 Nov;229:18-28. doi: 10.1016/j.ahj.2020.06.013. Epub 2020 Jun 25.
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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.
Karin Humphries, DSc principal investigator
Medicine, Cardiology, UBC, BC Centre for Improved Cardiovascular Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Introduction of a lower female hs-cTn threshold in people with Myocardial Infarction and Sex Differences, run by BC Centre for Improved Cardiovascular Health at 1 site in Canada.
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 4 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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?
Results are not available in the source record.
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?
Number of patients with all-cause mortality, non-fatal myocardial infarction, hospitalization for incident heart failure, or urgent/emergent coronary revascularization (percutaneous coronary intervention or coronary artery bypass surgery) (time frame: 2-year post index emergency department presentation). 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 NCT03819894, which also lists 1 linked publication.
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 9 Oct 2024.