Acute Coronary SyndromeHiSTORICNCT03005158
High-Sensitivity Cardiac Troponin On Presentation to Rule Out Myocardial Infarction
A study testing Validation Phase, Randomization Phase and Implementation Phase in people with Acute Coronary Syndrome and Myocardial Infarction, run by University of Edinburgh.
Trial summary
Patients with suspected acute coronary syndrome account for a tenth of all presentations to the Emergency Department and up to 40 per cent of unplanned hospital admissions. The majority of patients do not have a heart attack (myocardial infarction), and may be safely discharged from the Emergency Department. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Coronary Syndrome, Myocardial Infarction
- What is being tested?
- Validation Phase, Randomization Phase and Implementation Phase
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31,492 participants
- Where
- No sites listed yet
- Study dates
- Nov 2014to 2 Dec 2021
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All consecutive patients with suspected acute coronary syndrome
- High-sensitivity cardiac troponin I measured as part of routine clinical care
Who cannot join
- Patients who are not resident in Scotland
- Patients with ST-segment elevation myocardial infarction
- Patients presenting to hospital in cardiac arrest
- Patients with presentation high-sensitivity cardiac troponin I concentrations greater than sex-specific 99th centile thresholds
About this study
Official title: High-Sensitivity Cardiac Troponin On Presentation to Rule Out Myocardial Infarction (HiSTORIC): A Stepped Wedge Cluster Randomized Trial
Patients with suspected acute coronary syndrome account for a tenth of all presentations to the Emergency Department and up to 40 per cent of unplanned hospital admissions. The majority of patients do not have a heart attack (myocardial infarction), and may be safely discharged from the Emergency Department.
The investigators propose to evaluate whether the use of the HighSTEACS pathway in patients with suspected acute coronary syndrome reduces length of stay and allows more patients to be safely discharged from the Emergency Department. This pathways utilizes high-sensitivity cardiac troponin I testing and will rule out myocardial infarction if troponin concentrations are <5 ng/L on presentation, with further testing indicated at 3 hours only in those presenting early or with troponin concentrations between 5 ng/L and the 99th centile.
In six secondary and tertiary centres across Scotland, the investigators will introduce the pathway as part of a stepped wedge cluster randomized controlled trial. Sequential hypothesis testing will evaluate the efficacy and safety of the pathway. The primary efficacy end-point will be length of stay from time of presentation until final hospital discharge and the primary safety end-point will be survival free from type 1 or 4b myocardial infarction or cardiac death from discharge to 30 days. The study population will consist of those patients with cardiac troponin concentrations within the normal reference range (<99th centile) at presentation.
- Conditions
- Acute Coronary Syndrome, Myocardial Infarction
- Being tested
- Validation Phase, Randomization Phase, Implementation Phase
- Keywords
- High-sensitivity cardiac troponin I, Myocardial infarction, Acute coronary syndrome, Cluster-randomized trial
- Medical subject headings
- Acute Coronary Syndrome, Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Validation PhaseOther
Standard care across all sites during the validation phase will rule out myocardial infarction in those with presentation troponin below the 99th centile with greater than 6 hours of symptoms at the time of blood sampling. In those with less than 6 hours of symptoms, a second test will be measured 6- 12 hours after presentation.
Randomization PhaseOther
Standard care or HighSTEACS pathway.
Implementation PhaseOther
Implementation of the HighSTEACS pathway to rule out myocardial infarction in patients with suspected acute coronary syndrome. Myocardial infarction will be ruled out if presentation cardiac troponin concentrations are <5 ng/L in those with at least 2 hours of symptoms at the time of blood sampling. In patients with less than two hours of symptoms, or where cardiac troponin concentrations are between 5ng/L and the 99th centile, repeat testing will be recommended at 3 hours. Myocardial infarction will be ruled out at 3 hours if cardiac troponin concentrations are unchanged (<3 ng/L change) and remain ≤99th centile on retesting. Those remaining ≤99th centile on retesting but demonstrating a significant change will require admission for further testing at 6-12 hours.
| Study group | Role | What they receive |
|---|---|---|
| Validation Phase | Other | All six hospital sites currently use the ARCHITECT STAT high- sensitive troponin I assay in the assessment of patients with suspected acute coronary syndrome and use sex-specific thresholds upper reference limits (99th centile) to rule out myocardial infarction. This validation phase of up to 10 months will provide baseline information for each site on patients with suspected acute coronary syndrome in whom myocardial infarction is ruled out. Receives: Other: Validation Phase |
| Randomization Phase | Other | Participating centres will be randomized to implement the HighSTEACS pathway (intervention). The order of implementation will be randomized, with paired participating centres implementing in steps over a 6 month period. Receives: Other: Randomization Phase |
| Implementation Phase | Active comparator | A final phase of up to 10 months after implementation of the HighSTEACS pathway will be matched by calendar month in each site to that of the validation phase, allowing each participating centre to act as its own control and to adjust for seasonal differences in the incidence of myocardial infarction and mortality. Receives: Other: Implementation Phase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Length of hospital stay (minutes)
This time frame is unique to each patient
Measured: Length of time from initial presentation to the Emergency Department until final discharge from hospital, an average of 24 hours.
Type 1 or type 4b myocardial infarction or cardiac death after discharge and within 30 days of index admission
Measured: Hospital discharge to 30 days after initial presentation
Secondary outcomes (7)
Proportion of patients discharged directly home from the Emergency Department
Time frame of initial hospital episode is unique to each patient
Measured: Presentation to discharge from hospital, an average of 24 hours.
Type 1 or 4b Myocardial Infarction after hospital discharge (independently double adjudicated using all available clinical information)
An adjudicated diagnosis of type 1 and type 4b myocardial infarction will be made in line with the universal definition of myocardial infarction, using all available clinical information.
Measured: Hospital discharge to 30 days and 1 year after initial presentation
Cardiac death after hospital discharge (independently double adjudicated using all available clinical information)
Measured: Hospital discharge to 30 days and 1 year after initial presentation
Cardiovascular death after hospital discharge (independently double adjudicated using all available clinical information)
Measured: Hospital discharge to 30 days and 1 year after initial presentation
All-cause death after hospital discharge
Measured: Hospital discharge to 30 days and 1 year after initial presentation
Unplanned coronary revascularisation after hospital discharge (from cardiac intervention databases and case note review)
We will identify any patients who require unplanned percutaneous coronary intervention or coronary artery bypass grafting.
Measured: Hospital discharge to 30 days and 1 year after initial presentation
Proportion of patients re-attending the Emergency Department
Measured: Hospital discharge to 30 days and 1 year after initial presentation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2016 (estimated)
- Study startNov 2014
- Primary completion2 Jan 2017
- Study completion2 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Acute Coronary SyndromeStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- 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
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 31,492 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian, NHS Greater Glasgow and Clyde
- Responsible party
- Sponsor
- Investigators
- Nicholas L Mills, MD, PhD, Principal investigator, University of EdinburghIan Ford, PhD, Study chair, University of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03005158
- Sponsor's protocol ID
- PG/15/51/31596
- Acronym
- HiSTORIC
- Status last verified
- May 2024
- First submitted
- 15 Aug 2016
- Last updated
- 21 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Shah AS, Anand A, Sandoval Y, Lee KK, Smith SW, Adamson PD, Chapman AR, Langdon T, Sandeman D, Vaswani A, Strachan FE, Ferry A, Stirzaker AG, Reid A, Gray AJ, Collinson PO, McAllister DA, Apple FS, Newby DE, Mills NL; High-STEACS investigators. High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study. Lancet. 2015 Dec 19;386(10012):2481-8. doi: 10.1016/S0140-6736(15)00391-8. Epub 2015 Oct 8.
PubMed 26454362Shah ASV, Anand A, Chapman AR, Newby DE, Mills NL; High-STEACS Investigators. Measurement of cardiac troponin for exclusion of myocardial infarction - Authors' reply. Lancet. 2016 Jun 4;387(10035):2289-2291. doi: 10.1016/S0140-6736(16)30517-7. No abstract available.
PubMed 27302263Li Z, Doudesis D, Bularga A, Wereski R, Taggart C, Lowry MTH, Chapman AR, Tuck C, Ferry AV, Gray A, Newby DE, Anand A, Lee KK, Mills NL; HiSTORIC Trial Investigators. Safety of Using Risk Stratification Along With High-Sensitivity Cardiac Troponin in the Emergency Department: A Secondary Analysis. J Am Coll Cardiol. 2025 Nov 11;86(19):1738-1748. doi: 10.1016/j.jacc.2025.08.059.
PubMed 41193094Anand A, Lee KK, Chapman AR, Ferry AV, Adamson PD, Strachan FE, Berry C, Findlay I, Cruikshank A, Reid A, Collinson PO, Apple FS, McAllister DA, Maguire D, Fox KAA, Newby DE, Tuck C, Harkess R, Keerie C, Weir CJ, Parker RA, Gray A, Shah ASV, Mills NL; HiSTORIC Investigatorsdagger. High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction: A Stepped-Wedge Cluster Randomized Controlled Trial. Circulation. 2021 Jun 8;143(23):2214-2224. doi: 10.1161/CIRCULATIONAHA.120.052380. Epub 2021 Mar 23.
PubMed 33752439Ferry AV, Strachan FE, Stewart SD, Marshall L, Lee KK, Anand A, Shah ASV, Chapman AR, Mills NL, Cunningham-Burley S. Exploring Patient Experience of Chest Pain Before and After Implementation of an Early Rule-Out Pathway for Myocardial Infarction: A Qualitative Study. Ann Emerg Med. 2020 Apr;75(4):502-513. doi: 10.1016/j.annemergmed.2019.11.012. Epub 2020 Jan 23.
PubMed 31983496
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-Sensitivity Cardiac Troponin On Presentation to Rule Out Myocardial Infarction (HiSTORIC): A Stepped Wedge Cluster Randomized Trial
- ClinicalTrials.gov ID
- NCT03005158
- Acronym / sponsor ID
- HiSTORIC / PG/15/51/31596
- Conditions
- Acute Coronary Syndrome, Myocardial Infarction
- Keywords
- High-sensitivity cardiac troponin I, Myocardial infarction, Acute coronary syndrome, Cluster-randomized trial
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31,492 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian, NHS Greater Glasgow and Clyde
- Study start
- Nov 2014 (actual)
- Primary completion
- 2 Jan 2017 (actual)
- Study completion
- 2 Dec 2021 (actual)
- First posted
- 29 Dec 2016 (estimated)
- 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.
Patients with suspected acute coronary syndrome account for a tenth of all presentations to the Emergency Department and up to 40 per cent of unplanned hospital admissions. The majority of patients do not have a heart attack (myocardial infarction), and may be safely discharged from the Emergency Department.
The investigators propose to evaluate whether the use of the HighSTEACS pathway in patients with suspected acute coronary syndrome reduces length of stay and allows more patients to be safely discharged from the Emergency Department. This pathways utilizes high-sensitivity cardiac troponin I testing and will rule out myocardial infarction if troponin concentrations are <5 ng/L on presentation, with further testing indicated at 3 hours only in those presenting early or with troponin concentrations between 5 ng/L and the 99th centile.
In six secondary and tertiary centres across Scotland, the investigators will introduce the pathway as part of a stepped wedge cluster randomized controlled trial. Sequential hypothesis testing will evaluate the efficacy and safety of the pathway. The primary efficacy end-point will be length of stay from time of presentation until final hospital discharge and the primary safety end-point will be survival free from type 1 or 4b myocardial infarction or cardiac death from discharge to 30 days. The study population will consist of those patients with cardiac troponin concentrations within the normal reference range (<99th centile) at presentation.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Validation Phase | Other | Other: Validation PhaseAll six hospital sites currently use the ARCHITECT STAT high- sensitive troponin I assay in the assessment of patients with suspected acute coronary syndrome and use sex-specific thresholds upper reference limits (99th centile) to rule out myocardial infarction. This validation phase of up to 10 months will provide baseline information for each site on patients with suspected acute coronary syndrome in whom myocardial infarction is ruled out. |
| Randomization Phase | Other | Other: Randomization PhaseParticipating centres will be randomized to implement the HighSTEACS pathway (intervention). The order of implementation will be randomized, with paired participating centres implementing in steps over a 6 month period. |
| Implementation Phase | Active comparator | Other: Implementation PhaseA final phase of up to 10 months after implementation of the HighSTEACS pathway will be matched by calendar month in each site to that of the validation phase, allowing each participating centre to act as its own control and to adjust for seasonal differences in the incidence of myocardial infarction and mortality. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- All consecutive patients with suspected acute coronary syndrome
- High-sensitivity cardiac troponin I measured as part of routine clinical care
Key exclusion criteria (4 listed)
- Patients who are not resident in Scotland
- Patients with ST-segment elevation myocardial infarction
- Patients presenting to hospital in cardiac arrest
- Patients with presentation high-sensitivity cardiac troponin I concentrations greater than sex-specific 99th centile thresholds
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 |
|---|---|---|
| Validation PhaseStandard care across all sites during the validation phase will rule out myocardial infarction in those with presentation troponin below the 99th centile with greater than 6 hours of symptoms at the time of blood sampling. In those with less than 6 hours of symptoms, a second test will be measured 6- 12 hours after presentation. | Other | Validation Phase |
| Randomization PhaseStandard care or HighSTEACS pathway. | Other | Randomization Phase |
| Implementation PhaseImplementation of the HighSTEACS pathway to rule out myocardial infarction in patients with suspected acute coronary syndrome. Myocardial infarction will be ruled out if presentation cardiac troponin concentrations are <5 ng/L in those with at least 2 hours of symptoms at the time of blood sampling. In patients with less than two hours of symptoms, or where cardiac troponin concentrations are between 5ng/L and the 99th centile, repeat testing will be recommended at 3 hours. Myocardial infarction will be ruled out at 3 hours if cardiac troponin concentrations are unchanged (<3 ng/L change) and remain ≤99th centile on retesting. Those remaining ≤99th centile on retesting but demonstrating a significant change will require admission for further testing at 6-12 hours. | Other | Implementation Phase |
Primary outcome
Length of hospital stay (minutes)
Time frame: Length of time from initial presentation to the Emergency Department until final discharge from hospital, an average of 24 hours.
This time frame is unique to each patient
Type 1 or type 4b myocardial infarction or cardiac death after discharge and within 30 days of index admission
Time frame: Hospital discharge to 30 days after initial presentation
7 secondary outcomes
Proportion of patients discharged directly home from the Emergency Department
Time frame: Presentation to discharge from hospital, an average of 24 hours.
Type 1 or 4b Myocardial Infarction after hospital discharge (independently double adjudicated using all available clinical information)
Time frame: Hospital discharge to 30 days and 1 year after initial presentation
Cardiac death after hospital discharge (independently double adjudicated using all available clinical information)
Time frame: Hospital discharge to 30 days and 1 year after initial presentation
Cardiovascular death after hospital discharge (independently double adjudicated using all available clinical information)
Time frame: Hospital discharge to 30 days and 1 year after initial presentation
All-cause death after hospital discharge
Time frame: Hospital discharge to 30 days and 1 year after initial presentation
Unplanned coronary revascularisation after hospital discharge (from cardiac intervention databases and case note review)
Time frame: Hospital discharge to 30 days and 1 year after initial presentation
Proportion of patients re-attending the Emergency Department
Time frame: Hospital discharge to 30 days and 1 year after initial presentation
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 21 May 2024.
- Background: PubMed 26454362Shah AS, Anand A, Sandoval Y, Lee KK, Smith SW, Adamson PD, Chapman AR, Langdon T, Sandeman D, Vaswani A, Strachan FE, Ferry A, Stirzaker AG, Reid A, Gray AJ, Collinson PO, McAllister DA, Apple FS, Newby DE, Mills NL; High-STEACS investigators. High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study. Lancet. 2015 Dec 19;386(10012):2481-8. doi: 10.1016/S0140-6736(15)00391-8. Epub 2015 Oct 8.
- Background: PubMed 27302263Shah ASV, Anand A, Chapman AR, Newby DE, Mills NL; High-STEACS Investigators. Measurement of cardiac troponin for exclusion of myocardial infarction - Authors' reply. Lancet. 2016 Jun 4;387(10035):2289-2291. doi: 10.1016/S0140-6736(16)30517-7. No abstract available.
- Derived from this study: PubMed 41193094Li Z, Doudesis D, Bularga A, Wereski R, Taggart C, Lowry MTH, Chapman AR, Tuck C, Ferry AV, Gray A, Newby DE, Anand A, Lee KK, Mills NL; HiSTORIC Trial Investigators. Safety of Using Risk Stratification Along With High-Sensitivity Cardiac Troponin in the Emergency Department: A Secondary Analysis. J Am Coll Cardiol. 2025 Nov 11;86(19):1738-1748. doi: 10.1016/j.jacc.2025.08.059.
- Derived from this study: PubMed 33752439Anand A, Lee KK, Chapman AR, Ferry AV, Adamson PD, Strachan FE, Berry C, Findlay I, Cruikshank A, Reid A, Collinson PO, Apple FS, McAllister DA, Maguire D, Fox KAA, Newby DE, Tuck C, Harkess R, Keerie C, Weir CJ, Parker RA, Gray A, Shah ASV, Mills NL; HiSTORIC Investigatorsdagger. High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction: A Stepped-Wedge Cluster Randomized Controlled Trial. Circulation. 2021 Jun 8;143(23):2214-2224. doi: 10.1161/CIRCULATIONAHA.120.052380. Epub 2021 Mar 23.
- Derived from this study: PubMed 31983496Ferry AV, Strachan FE, Stewart SD, Marshall L, Lee KK, Anand A, Shah ASV, Chapman AR, Mills NL, Cunningham-Burley S. Exploring Patient Experience of Chest Pain Before and After Implementation of an Early Rule-Out Pathway for Myocardial Infarction: A Qualitative Study. Ann Emerg Med. 2020 Apr;75(4):502-513. doi: 10.1016/j.annemergmed.2019.11.012. Epub 2020 Jan 23.
- 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.
Nicholas L Mills, MD, PhD principal investigator
University of Edinburgh
Ian Ford, PhD study chair
University of Glasgow
Questions about this trial
What is this clinical trial studying?
A study testing Validation Phase, Randomization Phase and Implementation Phase in people with Acute Coronary Syndrome and Myocardial Infarction, run by University of Edinburgh.
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 2 inclusion and 4 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 21 May 2024. Status can change between updates, so confirm with the study contact before making plans.
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?
Length of hospital stay (minutes) (time frame: Length of time from initial presentation to the Emergency Department until final discharge from hospital, an average of 24 hours.). The study lists 2 primary outcomes in all. 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 NCT03005158, which also lists 5 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 21 May 2024.