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

• ClinicalTrials.gov Identifier: NCT03005158
• Recruitment Status: Unknown
• First Posted: December 29, 2016
• Last Update Posted: May 29, 2019
• Sponsor: University of Edinburgh
• Collaborators: NHS Lothian; NHS Greater Glasgow and Clyde
• Information provided by (Responsible Party): University of Edinburgh

Tracking Information

• First Submitted Date: August 15, 2016
• First Posted Date: December 29, 2016
• Last Update Posted Date: May 29, 2019
• Actual Study Start Date: November 2014
• Actual Primary Completion Date: January 2, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 28, 2016)

• 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 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 28, 2016)

• Proportion of patients discharged directly home from the Emergency Department [ Time Frame: Presentation to discharge from hospital, an average of 24 hours. ]
  Time frame of initial hospital episode is unique to each patient
• 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 ]
  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.
• 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 ]
  We will identify any patients who require unplanned percutaneous coronary intervention or coronary artery bypass grafting.
• Proportion of patients re-attending the Emergency Department [ Time Frame: Hospital discharge to 30 days and 1 year after initial presentation ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: December 28, 2016)

• Pre-specified sub-group analyses of the primary outcome [ Time Frame: 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 ]
  We will evaluate if the effect of intervention is significantly stronger or weaker in pre-specified sub-groups by assessing the co-primary endpoints in those who present with cardiac troponin <5 ng/L (low risk group), and in the whole population across different ages (considering age as a continuous variable), by duration of symptoms (considered as a continuous variable), by gender, by those who have or do not have a pre-existing history of ischaemic heart disease, by those with a presentation electrocardiogram suggesting ischaemia, by the GRACE risk score (considered as a continuous variable), and by day of patient presentation (assessing differences in weekday/weekend or routine/out-of-hours presentation).
• Cost-effectiveness analysis [ Time Frame: 1 year ]
  Based on costs of investigation and management in the year after initial hospital presentation

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Diagnostic

Condition

• Acute Coronary Syndrome
• Myocardial Infarction

Intervention

• Other: Validation Phase
  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.
• Other: Randomization Phase
  Standard care or HighSTEACS pathway.
• Other: Implementation Phase
  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 Arms

• Validation Phase
  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.
  Intervention: Other: Validation Phase
• Randomization Phase
  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.
  Intervention: Other: Randomization Phase
• Active Comparator: Implementation Phase
  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.
  Intervention: Other: Implementation Phase

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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 28, 2016): 39000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2, 2021
• Actual Primary Completion Date: January 2, 2017 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT03005158
• Other Study ID Numbers: PG/15/51/31596
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: University of Edinburgh
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Edinburgh
• Original Study Sponsor: Same as current

Collaborators

• NHS Lothian
• NHS Greater Glasgow and Clyde

Investigators

• Principal Investigator: Nicholas L Mills, MD, PhD; University of Edinburgh
• Study Chair: Ian Ford, PhD; University of Glasgow

• PRS Account: University of Edinburgh
• Verification Date: May 2019