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

Study Overview
=================
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.

Official Title
-----------------
High-Sensitivity Cardiac Troponin On Presentation to Rule Out Myocardial Infarction (HiSTORIC): A Stepped Wedge Cluster Randomized Trial

Conditions
-----------------
Acute Coronary Syndrome, Myocardial Infarction

Intervention / Treatment
-----------------
* Other: Validation Phase
* Other: Randomization Phase
* Other: Implementation Phase


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All consecutive patients with suspected acute coronary syndrome High-sensitivity cardiac troponin I measured as part of routine clinical care Exclusion Criteria: 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
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Validation Phase<br>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<br>* 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.<br>|
| Other: Randomization Phase<br>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<br>* Standard care or HighSTEACS pathway.<br>|
| Active Comparator: Implementation Phase<br>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<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients discharged directly home from the Emergency Department | Time frame of initial hospital episode is unique to each patient | 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. | 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 | 
| 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. | Hospital discharge to 30 days and 1 year after initial presentation | 
| Proportion of patients re-attending the Emergency Department |  | Hospital discharge to 30 days and 1 year after initial presentation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
High-sensitivity cardiac troponin I, Myocardial infarction, Acute coronary syndrome, Cluster-randomized trial