Rapid Use of High-sensitive Cardiac Troponin I for ruling-in and Ruling-out of Acute Myocardial Infarction

NCT ID: NCT03634384

Last Updated: 2018-12-05

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-11-21
• Study Completion Date: 2020-12-31

Brief Summary

Early rule-in or rule-out of myocardial infarction (MI) is essential in patients presenting to the Emergency Department with chest pain. Recently, the European Society of Cardiology has suggested an accelerated 0h/1h algorithm to rule-in or rule-out MI as a valid alternative to the standard 0h/3h approach. So far, the 0h/1h algorithm has only been validated for certain high-sensitive Troponin assays. Moreover, it is unknown if MI can be ruled-out by measuring hs-cTn already at 30 minutes (0h/30m) after presentation to the Emergency Department.

This prospective cohort study aims to investigate, if a high-sensitive Troponin assay can rule-in or rule-out MI, when using a 0h/30m and a 0h/1h algorithm. Serial blood samples will be drawn from each patient and used for biomarker analysis. In addition, patients will be asked to complete a detailed questionnaire on chest pain characteristics.

Detailed Description

Background: Chest pain is a key symptom of acute coronary syndrome (ACS), but can also represent other cardiac and non-cardiac diseases. Rapid identification of ACS in terms of 'rule-in' or 'rule-out' is essential in order to minimize treatment delay and time to discharge. In the absence of ST-segment elevation myocardial infarction (STEMI) at initial ACS evaluation, the European Society of Cardiology guidelines recommend repeated measurements of high-sensitive cardiac troponin (hs-cTn) at presentation (0h) and 3 hours (3h) after presentation to rule-in and rule-out myocardial infarction (MI). An accelerated algorithm for ruling-in and ruling-out MI after 1h (0h/1h algorithm) has recently been suggested by the European Society of Cardiology as a valid alternative to the standard approach. The novel 0h/1h algorithm has only been validated for certain hs-cTn assays. However, routine use of the 0h/1h algorithm is still not widely implemented, as further data on algorithm performance are warranted.

A study of patients undergoing transcoronary ablation of septal hypertrophy, a clinical model of MI, shows that troponin concentrations measured by a hs-cTn assay significantly increase already after 15 minutes. This indicates that it may be possible to evaluate troponin dynamics even earlier than suggested by the 0h/1h algorithm. So far, no large-scale studies have included measurements of hs-cTn at 30m, and no 0h/30m algorithm has been derived. Therefore it is unknown if rule-in and rule-out of MI can be done safely using a 0h/30m algorithm.

Aim: To investigate if a high-sensitive Troponin Assay can rule-in or rule-out MI, when using a 0h/30m and a 0h/1h algorithm.

Patients and methods: This prospective cohort study will include patients presenting to the Emergency Department with chest pain suggestive of ACS. The study is designed to enroll 1.000 patients with complete blood samples (0h, 30m, 1h and 3h).

The expected incidence of MI in our population is inevitably low due to pre-hospital risk-stratification based on point-of-care troponin and electrocardiogram evaluation in the ambulance. Thus, patients with a very high pre-test probability of MI will be admitted to tertiary care centers with cardiac catheterization facilities rather than a regional hospital as in present study. Pilot study calculations estimate an expected prevalence of MI in our study cohort of approximately 7.4%. Assuming a negative predictive value of 99.7% in the rule-out group, a distribution with 7% patients in the rule-in group and 20% assigned to the observational zone (patients who can't be stratified to either the rule-out or the rule-in group), enrolment of at least 500 patients for derivation of the algorithms and at least 500 for the validation of the respective algorithms will provide an acceptable lower boundary of 98.2% of the two-sided 95% confidence interval.

All patients aged ≥18 years referred to the emergency department at Randers Regional Hospital, Randers, Denmark with chest pain and admitted on the suspicion of ACS will be eligible for the study. Patients will be recruited after initial contact with an emergency department nurse when results of an electrocardiogram as well as vital sign parameters (blood pressure, heart rate, peripheral oxygen saturation, respiratory rate and temperature) are available. Patients <18 years of age, with STEMI at admission, in dialysis treatment or pregnant will be excluded.

The study is conducted in accordance with the Declaration of Helsinki. Oral and written consent will be obtained. Patients will be asked for informed consent to have information passed on from the electronic patient journal regarding gender, age, medicine, previous MI and co-morbidity for use in this study only. Patients declining to participate will receive standard treatment.

Serial blood samples will be drawn at 0h (admission), 30m, 1h and 3h. The blood samples will be analyzed using high-sensitive troponin assays. Additional blood will be stored for each time point to establish a research biobank. Troponin values and troponin dynamics will be paired with final diagnosis for each patient. Two independent physicians will adjudicate the patients' final diagnosis based on data from the electronic patient journal (including physical examination, patient history, laboratory results, electrocardiogram, and other examinations). In cases of disagreement, a consensus decision will be reached after a case review. The treating physician will be blinded to test results at 30m and 1h, with the final therapeutic decision being left to the discretion of the attending physician and relying on troponin measurements at 0h and 3h only. All patients will be asked to complete a questionnaire on, e.g., time of chest pain onset and peak, chest pain characteristics (localization, radiation, sensation), additional symptoms at presentation (diaphoresis, nausea, abdominal pain, syncope, dyspnoea, palpitations), height and weight, smoking status and family history of coronary artery disease.

Significance: This study challenges existing time limits for ACS evaluation by investigating the diagnostic value of hs-cTnI measurements at 30m. If our study shows that rule-out of MI can be performed safely at 30m, ACS evaluation can potentially be accelerated even further. Furthermore, our study will provide data on the performance of the 0h/1h algorithm in a Danish patient cohort. If this study demonstrates that the 0h/1h diagnostic algorithm can be used to safely rule-out MI in a patient cohort with a different risk profile, it can contribute to the acceptance of novel accelerated diagnostic approaches and favor global implementation of the 0h/1h algorithm.

Conditions

Myocardial Infarction; Chest Pain

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Derivation cohort

We include eligible patients presenting with chest pain suggestive of myocardial infarction to the emergency department (see eligibility).

For the primary study patients will be divided into two groups: 500 patients will serve as derivation cohort.

No interventions assigned to this group

Validation cohort

We include eligible patients presenting with chest pain suggestive of myocardial infarction to the emergency department (see eligibility).

For the primary study patients will be divided into two groups: 500 patients will serve as validation cohort.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Patients over 18 years of age
• Admitted to the Emergency Department
• Chest pain suggestive of myocardial infarction.

Exclusion Criteria

• Patients <18 years of age
• STEMI at admission
• Dialysis
• Pregnancy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Randers Regional Hospital

OTHER

Sponsor Role: collaborator

Aarhus University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Bo Løfgren

Professor, MD, PhD, FESC

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bo Løfgren, Professor, MD, PhD

Role: STUDY_DIRECTOR

Randers Regional Hospital

Camilla Bang, MD

Role: PRINCIPAL_INVESTIGATOR

Randers Regional Hospital

Camilla Hansen, MD

Role: PRINCIPAL_INVESTIGATOR

Randers Regional Hospital

Locations

Randers Regional Hospital

Randers, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Bo Løfgren, Professor, MD, PhD

Role: CONTACT

bl@clin.au.dk

+4578420000

Facility Contacts

Bo Løfgren, Professor, MD, PhD

Role: primary

bl@clin.au.dk

+45 78420000

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Provided Documents

Document Type: Study Protocol

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Other Identifiers

54559

Identifier Type: -

Identifier Source: org_study_id