Very Early veRsus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes

Study Overview
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Brief Summary
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The aim of this study is to evaluate if acute invasive coronary evaluation and treatment conducted within 12 hours of diagnosis improves clinical outcome compared to a deferred, subacute strategy in patients with unstable angina pectoris (UAP) / non-ST segment elevation myocardial infarction (NSTEMI) Acute coronary syndrome (ACS) Furthermore, in an observational design the potential clinical benefit of coronary computed tomography angiography (CCTA) to select patients for invasive investigation and treatment in the two treatment arms (acute vs deferred) is evaluated. The following main hypothesis will be tested: Very early invasive coronary investigation improves clinical outcome in patients with UAP/NSTEMI-ACS CCTA performed before invasive coronary investigation will improve clinical management of patients with UAP/NSTEMI-ACS

Detailed Description
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MATERIAL Consecutive patients suspected of UAP/NSTEMI will be screened for participation in the study. Only patients deemed clinically suited for invasive coronary evaluation and treatment will be included. A total of 2500 patients will be included in the trial at Departments of Cardiology of Danish Hospitals. METHODS If the patients accept participation in the trial a computerized 1:1 randomization for acute invasive coronary evaluation (Intervention group - within 12 hours from time of diagnosis) or for deferred invasive evaluation (Control group - no later than 72 hours from time of diagnosis). All included patients undergo CCTA prior to invasive coronary evaluation, except for patient with moderately reduced renal function (se below). The treating invasive cardiologist will remain blinded to observational CCTA data. Patients with endstage renal disease in dialysis may undergo CCTA. CCTA data recorded as part of the research protocol will not be made available for the treating physician. SECONDARY EXCLUSION Based on post-hoc expert clinical evaluation patients not having UAP/NSTEMI-ACS (arrythmias, pulmonary oedema, missed STEMI, pneumonia, Pulmonary emboli) will be excluded from analysis of difference between outcome measures in treatment strategy groups. STATISTICAL METHODS Patients with UAP/NSTEMI-ACS are based on previous studies expected to have an event rate of 15% within 1 year and 50% at 4 years of the primary combined endpoint: all cause mortality, non-fatal recurrent myocardial infarction, hospitalisation for refractory ischemia or heart failure. In order to demonstrate a reduction of 25% within 3 years 711 patients in each group are needed. The study is powered to detect a clinical relevant reduction in mortality or heart failure hospitalization with a total of 2500 patients.

Official Title
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Entire Danish Initiative To ImrpOve Revascularization Strategies (EDITORS) - A Randomised Evaluation of Clinical Outcome After Acute or Deferred Invasive Intervention Integrated With MDCT Imaging in Patients With Acute Coronary Syndromes

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Procedure: Invasive coronary evaluation (Deferred)
* Procedure: Invasive coronary evaluation (Acute)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with clinical suspicion of of UAP/NSTEMI acute coronary syndrome deemed suitable for invasive evaluation and treatment will be included in the study. Age> 18 years At least one of the following: ECG abnormalities suggestive of myocardial ischemia (newly developed ST segment depression, horizontal or descending >= 0,05mV in two anatomically adjacent leads and/or T-wave inversion >0,01 mV in two leads with prominent R wave or R/S ratio >1 Elevated myocardial ischemia biomarkers (Troponin, CK-MB) Exclusion Criteria: Pregnancy Circumstances preventing the patient from reading and/or understanding the research protocol information Clinical indication for acute invasive coronary angiography - severe chest pain despite intravenous nitroglycerin infusion or hemodynamic instability Expected survival of less than 1 year Known allergy/hypersensitivity of pharmacological platelet inhibitors and/or iodine contrast that cannot be prevented medically Patients with known eGFR below 60 ml/min will not undergo CCTA, whereas patients in dialysis will undergo the entire study protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Deferred invasive evaluation<br>Deferred invasive coronary evaluation and revascularization (PCI/CABG) within 72 hours from time of clinical diagnosis (CONTROL group) | Procedure: Invasive coronary evaluation (Deferred)<br>* Invasive coronary angiography and revascularization (PCI/CABG)<br>|
| Experimental: Very early invasive evaluation<br>Acute invasive coronary evaluation within 12 hours from time of diagnosis - INTERVENTION group | Procedure: Invasive coronary evaluation (Acute)<br>* Invasive coronary angiography and revascularization (PCI/CABG)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite clinical endpoint | Composite endpoint of all cause mortality, non-fatal recurrent acute myocardial infarction, hospitalisation for refractory ischemia (acute coronary syndrome) or heart failure | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding | Major and minor bleeding according to TIMI and BARC classification systems | During index hospitalization - an expected average of 5 days | 
| Non-bleeding, invasive procedure related complications | Invasive procedure related acute myocardial infarction, embolic stroke, cardiac arrest | During index hospitalization - an expected average of 5 days | 
| Death | All-cause death | 3 and 5 years | 
| Non-fatal acute myocardial infarction |  | 3 and 5 years | 
| Hospital admittance due to refractory myocardial ischemia (acute coronary syndrome) |  | 3 and 5 years | 
| Repeat coronary revascularization | Recorded from 30 days post-index procedure | 3 and 5 years | 
| Hospital admittance due to left ventricular heart failure |  | 3 and 5 years | 
| GRACE Risk Score | All primary and secondary endpoints stratified by GRACE score at a threshold of 140 | 3 and 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary Stenosis, Coronary Artery Disease, Acute coronary syndrome, Percutaneous Coronary Intervention, Multidetector Computed Tomography