High-Sensitivity Cardiac Troponin On Presentation to Rule Out Myocardial Infarction

NCT03005158 | Completed DMC

• 1 other identifier: PG/15/51/31596
• Study Type: interventional
• Target: 31,492
• Locations: 0 countries
• Sites: N/A

Brief 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. 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

Keywords

High-sensitivity cardiac troponin I; Myocardial infarction; Acute coronary syndrome; Cluster-randomized trial

Outcome Measures

Primary Outcomes (2)

• Length of hospital stay (minutes)

  This time frame is unique to each patient

  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

  Hospital discharge to 30 days after initial presentation

Secondary Outcomes (7)

• Proportion of patients discharged directly home from the Emergency Department

  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)

  Hospital discharge to 30 days and 1 year after initial presentation

• Cardiac death after hospital discharge (independently double adjudicated using all available clinical information)

  Hospital discharge to 30 days and 1 year after initial presentation

• Cardiovascular death after hospital discharge (independently double adjudicated using all available clinical information)

  Hospital discharge to 30 days and 1 year after initial presentation

• All-cause death after hospital discharge

  Hospital discharge to 30 days and 1 year after initial presentation

Other Outcomes (2)

• Pre-specified sub-group analyses of the primary outcome

  length of hospital stay defined as the length of time from initial presentation to the Emergency Department until final discharge from hospital; safety follow-up time frame of 30 days and 1 year after hospital discharge

• Cost-effectiveness analysis

  1 year

Study Arms (3)

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.

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.

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.

Other: Implementation Phase

Interventions

Validation Phase OTHER

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.

Validation Phase

Randomization Phase OTHER

Standard care or HighSTEACS pathway.

Randomization Phase

Implementation Phase OTHER

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.

Implementation Phase

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All consecutive patients with suspected acute coronary syndrome
• High-sensitivity cardiac troponin I measured as part of routine clinical care

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator
• NHS Greater Glasgow and Clyde: collaborator

Related Publications (5)

• 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.

  PMID: 26454362 BACKGROUND

• Shah 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.

  PMID: 27302263 BACKGROUND

• Li 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.

  PMID: 41193094 DERIVED

• Anand 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.

  PMID: 33752439 DERIVED

• Ferry 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.

  PMID: 31983496 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome; Myocardial Infarction

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Nicholas L Mills, MD, PhD

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

• Ian Ford, PhD

  University of Glasgow

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2016
• First Posted: December 29, 2016
• Study Start: November 1, 2014
• Primary Completion: January 2, 2017
• Study Completion: December 2, 2021
• Last Updated: May 21, 2024

Record last verified: 2024-05