Clinical trial NCT01852123: High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome
Official title: High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Coronary Syndrome
Myocardial Infarction
Keywords: High-sensitivity troponin assay
Myocardial infarction
Unstable angina
Myocardial injury
Cluster randomized trial
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: NHS Lothian
name: NHS Greater Glasgow and Clyde
name: Abbott Diagnostics Division
First posted: 2013-05-13
Enrollment: 48282
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: In patients with chest pain the diagnosis of a heart attack (myocardial infarction) is made where there is evidence of heart muscle damage using a blood test to measure the heart muscle protein troponin. A new a more sensitive troponin test may help us to identify patients with myocardial infarction more easily.

The investigators propose to evaluate whether use of a novel high-sensitivity troponin test to lower the threshold for diagnosis of myocardial infarction is appropriate. If increased sensitivity does not reduce specificity for the diagnosis, then this new test will improve patient outcome through better targeting of therapies for coronary heart disease. However, if increased sensitivity leads to poor specificity, then patients may be misdiagnosed and given inappropriate cardiac medications with potentially detrimental outcomes.

In ten secondary and tertiary care hospitals across Scotland, the investigators will undertake a stepped wedge cluster randomized controlled trial of the implementation of a novel high-sensitivity troponin test. The primary end-point will be the one-year rate of cardiovascular death or recurrent myocardial infarction. This will establish whether the introduction of this high-sensitivity troponin test into routine clinical practice is beneficial to patient management and outcomes.

A subset of patients will be asked to give consent for inclusion into a sub-study that will permit storage of blood samples and will require the completion of a survey during the index admission and after 6 and 12 months of follow up.


Eligibility criteria: Inclusion criteria:

* Suspected acute coronary syndrome
* Troponin I measurement as part of routine clinical care

Exclusion criteria:

- None

Primary outcomes:
measure: Recurrent myocardial infarction or cardiovascular death at 1 year
timeFrame: 1 year
Secondary outcomes:
measure: Duration of stay
timeFrame: Initial episode
measure: Recurrent myocardial infarction
timeFrame: 1 year
measure: Unplanned coronary revascularization
timeFrame: 1 year
measure: Cardiovascular death
timeFrame: 1 year
measure: All cause death
timeFrame: 1 year
measure: Heart failure hospitalization
timeFrame: 1 year
measure: Major hemorrhage
timeFrame: 1 year
measure: Minor hemorrhage
timeFrame: 1 year
measure: Recurrent unplanned hospitalization excluding acute coronary syndrome
timeFrame: 30 days
measure: Non-cardiovascular death
timeFrame: 1 year
Other outcomes:
measure: Physician diagnosis on discharge
timeFrame: Duration of the index hospital stay, an expected average of 2 weeks
measure: Sensitivity and specificity of sex-specific thresholds for the diagnosis of myocardial infarction
timeFrame: 3 months
measure: Evaluate thresholds to rule out myocardial infarction on presentation and change criteria to rule in myocardial infarction with serial sampling.
timeFrame: 6 months
Locations:
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
state: Lothian
Study officials:
affiliation: University of Edinburgh
name: Nicholas L Mills, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Glasgow
name: Ian Ford, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: Bularga A, Taggart C, Mendusic F, Kimenai DM, Wereski R, Lowry MTH, Lee KK, Ferry AV, Stewart SS, McAllister DA, Shah ASV, Anand A, Newby DE, Mills NL, Chapman AR; High-Sensitivity Troponin in the Evaluation of Patients with Suspected Acute Coronary Syndrome (High-STEACS) Investigators. Assessment of Oxygen Supply-Demand Imbalance and Outcomes Among Patients With Type 2 Myocardial Infarction: A Secondary Analysis of the High-STEACS Cluster Randomized Clinical Trial. JAMA Netw Open. 2022 Jul 1;5(7):e2220162. doi: 10.1001/jamanetworkopen.2022.20162.
citation: Doudesis D, Lee KK, Yang J, Wereski R, Shah ASV, Tsanas A, Anand A, Pickering JW, Than MP, Mills NL; High-STEACS Investigators. Validation of the myocardial-ischaemic-injury-index machine learning algorithm to guide the diagnosis of myocardial infarction in a heterogenous population: a prespecified exploratory analysis. Lancet Digit Health. 2022 May;4(5):e300-e308. doi: 10.1016/S2589-7500(22)00025-5.
citation: Wereski R, Kimenai DM, Taggart C, Doudesis D, Lee KK, Lowry MTH, Bularga A, Lowe DJ, Fujisawa T, Apple FS, Collinson PO, Anand A, Chapman AR, Mills NL. Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction. Circulation. 2021 Aug 17;144(7):528-538. doi: 10.1161/CIRCULATIONAHA.121.054302. Epub 2021 Jun 25.
citation: Hung J, Roos A, Kadesjo E, McAllister DA, Kimenai DM, Shah ASV, Anand A, Strachan FE, Fox KAA, Mills NL, Chapman AR, Holzmann MJ. Performance of the GRACE 2.0 score in patients with type 1 and type 2 myocardial infarction. Eur Heart J. 2021 Jul 8;42(26):2552-2561. doi: 10.1093/eurheartj/ehaa375.
citation: Lee KK, Ferry AV, Anand A, Strachan FE, Chapman AR, Kimenai DM, Meex SJR, Berry C, Findlay I, Reid A, Cruickshank A, Gray A, Collinson PO, Apple FS, McAllister DA, Maguire D, Fox KAA, Newby DE, Tuck C, Keerie C, Weir CJ, Shah ASV, Mills NL; High-STEACS Investigators. Sex-Specific Thresholds of High-Sensitivity Troponin in Patients With Suspected Acute Coronary Syndrome. J Am Coll Cardiol. 2019 Oct 22;74(16):2032-2043. doi: 10.1016/j.jacc.2019.07.082.
citation: Chapman AR, Adamson PD, Shah ASV, Anand A, Strachan FE, Ferry AV, Lee KK, Berry C, Findlay I, Cruikshank A, Reid A, Gray A, Collinson PO, Apple F, McAllister DA, Maguire D, Fox KAA, Vallejos CA, Keerie C, Weir CJ, Newby DE, Mills NL; High-STEACS Investigators. High-Sensitivity Cardiac Troponin and the Universal Definition of Myocardial Infarction. Circulation. 2020 Jan 21;141(3):161-171. doi: 10.1161/CIRCULATIONAHA.119.042960. Epub 2019 Oct 7.
citation: Bularga A, Lee KK, Stewart S, Ferry AV, Chapman AR, Marshall L, Strachan FE, Cruickshank A, Maguire D, Berry C, Findlay I, Shah ASV, Newby DE, Mills NL, Anand A. High-Sensitivity Troponin and the Application of Risk Stratification Thresholds in Patients With Suspected Acute Coronary Syndrome. Circulation. 2019 Nov 5;140(19):1557-1568. doi: 10.1161/CIRCULATIONAHA.119.042866. Epub 2019 Sep 1.
citation: Ferry AV, Anand A, Strachan FE, Mooney L, Stewart SD, Marshall L, Chapman AR, Lee KK, Jones S, Orme K, Shah ASV, Mills NL. Presenting Symptoms in Men and Women Diagnosed With Myocardial Infarction Using Sex-Specific Criteria. J Am Heart Assoc. 2019 Sep 3;8(17):e012307. doi: 10.1161/JAHA.119.012307. Epub 2019 Aug 20.
citation: Neumann JT, Twerenbold R, Ojeda F, Sorensen NA, Chapman AR, Shah ASV, Anand A, Boeddinghaus J, Nestelberger T, Badertscher P, Mokhtari A, Pickering JW, Troughton RW, Greenslade J, Parsonage W, Mueller-Hennessen M, Gori T, Jernberg T, Morris N, Liebetrau C, Hamm C, Katus HA, Munzel T, Landmesser U, Salomaa V, Iacoviello L, Ferrario MM, Giampaoli S, Kee F, Thorand B, Peters A, Borchini R, Jorgensen T, Soderberg S, Sans S, Tunstall-Pedoe H, Kuulasmaa K, Renne T, Lackner KJ, Worster A, Body R, Ekelund U, Kavsak PA, Keller T, Lindahl B, Wild P, Giannitsis E, Than M, Cullen LA, Mills NL, Mueller C, Zeller T, Westermann D, Blankenberg S; COMPASS-MI Study Group. Application of High-Sensitivity Troponin in Suspected Myocardial Infarction. N Engl J Med. 2019 Jun 27;380(26):2529-2540. doi: 10.1056/NEJMoa1803377.
citation: Chapman AR, Fujisawa T, Lee KK, Andrews JP, Anand A, Sandeman D, Ferry AV, Stewart S, Marshall L, Strachan FE, Gray A, Newby DE, Shah ASV, Mills NL. Novel high-sensitivity cardiac troponin I assay in patients with suspected acute coronary syndrome. Heart. 2019 Apr;105(8):616-622. doi: 10.1136/heartjnl-2018-314093. Epub 2018 Nov 15.
citation: Chapman AR, Hesse K, Andrews J, Lee KK, Anand A, Shah ASV, Sandeman D, Ferry AV, Jameson J, Piya S, Stewart S, Marshall L, Strachan FE, Gray A, Newby DE, Mills NL. High-Sensitivity Cardiac Troponin I and Clinical Risk Scores in Patients With Suspected Acute Coronary Syndrome. Circulation. 2018 Oct 16;138(16):1654-1665. doi: 10.1161/CIRCULATIONAHA.118.036426.
citation: Shah ASV, Anand A, Strachan FE, Ferry AV, Lee KK, Chapman AR, Sandeman D, Stables CL, Adamson PD, Andrews JPM, Anwar MS, Hung J, Moss AJ, O'Brien R, Berry C, Findlay I, Walker S, Cruickshank A, Reid A, Gray A, Collinson PO, Apple FS, McAllister DA, Maguire D, Fox KAA, Newby DE, Tuck C, Harkess R, Parker RA, Keerie C, Weir CJ, Mills NL; High-STEACS Investigators. High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial. Lancet. 2018 Sep 15;392(10151):919-928. doi: 10.1016/S0140-6736(18)31923-8. Epub 2018 Aug 28.
citation: Miller-Hodges E, Anand A, Shah ASV, Chapman AR, Gallacher P, Lee KK, Farrah T, Halbesma N, Blackmur JP, Newby DE, Mills NL, Dhaun N. High-Sensitivity Cardiac Troponin and the Risk Stratification of Patients With Renal Impairment Presenting With Suspected Acute Coronary Syndrome. Circulation. 2018 Jan 30;137(5):425-435. doi: 10.1161/CIRCULATIONAHA.117.030320. Epub 2017 Oct 4.
citation: Chapman AR, Anand A, Boeddinghaus J, Ferry AV, Sandeman D, Adamson PD, Andrews J, Tan S, Cheng SF, D'Souza M, Orme K, Strachan FE, Nestelberger T, Twerenbold R, Badertscher P, Reichlin T, Gray A, Shah ASV, Mueller C, Newby DE, Mills NL. Comparison of the Efficacy and Safety of Early Rule-Out Pathways for Acute Myocardial Infarction. Circulation. 2017 Apr 25;135(17):1586-1596. doi: 10.1161/CIRCULATIONAHA.116.025021. Epub 2016 Dec 29.