CAOCT: Intra CoronAry Optical Computerized Tomography in out-of Hospital Cardiac Arrest Patients

Study Overview
=================
Brief Summary
-----------------
Out-of-hospital cardiac arrest (OHCA) is a leading cause of sudden death in Europe and the United States. Mortality is currently close to 40% among those patients who had been successfully resuscitated after OHCA associated with ventricular fibrillation or pulseless ventricular tachycardia . Coronary artery disease is observed in up to 70% of patients with OHCA and immediate coronary angiography . Current European and American guidelines recommend immediate coronary angiography with primary angioplasty in OHCA patients with ST-segment elevation on ECG after successful resuscitation . Furthermore, the identification of the culprit lesion by coronary angiography among patients with an acute coronary syndrome (ACS) and no OHCA is challenging. In a recent cardiac magnetic resonance study, Heitner et al. found that in almost half of the patients with non-ST segment elevation ACS, the culprit lesion was not properly detected or identified by coronary angiography. In the Coronary Angiography after cardiac arrest (COACT) trial, a randomized controlled trial comparing immediate versus delayed coronary angiography after OHCA in patients without ST segment elevation on ECG, some degree of coronary artery disease was found in 64.5% of the patients in the immediate angiography group and an unstable coronary lesion was identified in only 13.6% of the patients. However, in survivors of OHCA without ST segment elevation on ECG, the use of intra coronary optical computerized tomography (OCT) led to identification of plaque rupture (27%), plaque erosion (36%) and coronary thrombosis (59%) undetected on angiography. There is hence a clear need to improve causality diagnosis among patients resuscitated after OHCA and without ST segment elevation on ECG, and, in the case of coronary artery disease detection, to better identify the culprit vessel/lesion ultimately leading to a targeted treatment. These are the reasons why we have designed a prospective, multi-centre, single cohort, diagnostic accuracy study: to better explore the incidence of a true ACS among OHCA survivors and to evaluate the accuracy of angiography to detect the culprit lesion when compared to OCT.

Official Title
-----------------
CAOCT Study is a Prospective, Multi-centre, Single Cohort, Diagnostic Accuracy Study, Planned to Include 131 Patients in About 3 European Countries After Successful Return of Spontaneous Circulation After Out of Hospital Cardiac Arrest

Conditions
-----------------
Out of Hospital Cardiac Arrest

Intervention / Treatment
-----------------
* Procedure: Optical Coherence Tomography
* Procedure: Coronary Angiography
* Procedure: Per cutaneous coronary intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects of age ≥ 18 years and ≤ 85 years, The delay between OHCA and basic life support (no flow period) is ≤ 5 minutes, First recorded ECG exhibits a shockable rhythm (ventricular tachycardia/ventricular fibrillation). Exclusion Criteria: The patient is still receiving cardiac massage at the time of admission in the cath-lab, There is an obvious extra cardiac cause to the cardiac arrest (suicide, drowning, hanging, trauma etc.), The patient has prior coronary artery bypass grafting, The patient has incessant ventricular tachycardia/fibrillation, The patient has at least one acute or chronic coronary occlusion of an epicardial coronary artery ≥2.0mm of diameter on conventional angiography, The coronary artery anatomy does not allow realization of three vessels OCT according to the interventional cardiologist (severe tortuosity, severe calcifications etc.), The patient is in cardiogenic shock or with a left ventricular assistance device, The post ROSC ECG (12 leads) exhibits ST segment elevation (defined as a ≥1mm ST segment elevation in two or more contiguous standard leads or as a ≥2mm ST segment elevation in two or more precordial leads), The post ROSC ECG (12 leads) exhibits new left bundle block branch (LBBB).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

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

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

Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Optical Coherence Tomography|OCT (DragonFly, Abbott Vascular) will be performed after angiography. OCT images will be acquired using the 6F guide catheter compatible DragonFly System (Abbott Vascular, Santa Clara, USA). The catheter will be introduced into the first coronary artery via a standard 0.014-inch angioplasty wire, after prior injection of an intracoronary bolus of nitro-glycerine (according to the hemodynamic conditions of the patient). To remove all blood adequately from the imaging site, nonocclusive flushing will be performed using continuously inject via an automated power injector, and the OCT catheter will be pulled back at a speed of 18 mm/second to guarantee sufficient time to acquire images of a 54 mm long segment (frame density: 10 frames/mm).|
|Procedure: Coronary Angiography|The coronary angiography will be performed according to the strategies described in the consensus statement from the European Association for Percutaneous Cardiovascular Interventions (EAPCI)/Stent for Life (SFL) groups.Transradial or transfemoral 6F/7F approaches are recommended. The choice of diagnostic catheters, guiding catheters, guidewires, pre-dilatation, atherectomy devices, and post dilatation is let to the investigator's discretion.|
|Procedure: Per cutaneous coronary intervention|Based on coronary angiography and OCT analyses by the investigators, PCI will be performed, preferentially for the identified culprit lesion(s) only. The guiding catheters, guidewires, pre-dilatation, atherectomy devices, and post dilatation are left to physician discretion. The use of semi- or non-compliant balloons number and diameter of drug eluting stent(s) will also be left to the physician discretion, but post dilation will be strongly recommended in case of PCI. OCT can eventually be performed after stent implantation to guide, post dilation strategy.|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of misclassification of at least one unstable coronary artery lesion per patient, between core lab angiography and core lab OCT assessments. | The core lab OCT analysis is considered as the gold standard for unstable coronary lesion detection. Detection of unstable coronary lesion by OCT includes atherosclerosis plaque rupture/erosion and thrombosis, calcified noduli with apposed thrombus, and spontaneous coronary dissection. Angiographically, unstable coronary lesions are defined as coronary lesions with at least >50% stenosis and the presence of characteristics of plaque disruption, including irregularity, dissection, haziness, or thrombus. A misclassification is either an unstable lesion detected by core lab OCT and misdiagnosed or undiagnosed on core lab angiography, or an unstable lesion as defined on core lab angiography but without plaque rupture/erosion and thrombosis, calcified noduli with apposed thrombus, and spontaneous coronary dissection on core lab OCT. | Intra operative, up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The misclassification rate per coronary artery segment analysis, on angiography versus OCT (both techniques peri procedural as assessed by investigators) | All analysable coronary segments according to the American Heart Association (AHA) classification (8) will be included in the final analysis. All paired (peri procedural as assessed by investigators angio and OCT) analysed segments will be included in the analysis. | Intra operative, up to 12 months | 
| The percentage of patients for whom peri procedural OCT findings change their management (including revascularization strategy) when compared to the initial therapeutic strategy decided upon after investigator-assessed on-line angiography | This endpoint represents a comparison between the management of the culprit lesion identified by the investigator after coronary angiography (and strictly captured in the electronic Case Report Form (eCRF) before OCT) and management of the culprit lesion as identified after OCT. Change in interventional management will include patients in whom an initially planned PCI was hold off after OCT and, vice versa, those declined a PCI in whom a PCI was finally decided after OCT. A patient for whom angiography and OCT-based diagnosis would lead to PCI of an additional but distinct coronary segment within the same vessel will be considered as a change in PCI plan. | Intra operative, up to 12 months | 
| The percentage of unstable lesions (core lab OCT) intended to be left untreated by PCI after peri procedural (as assessed by investigators) angiography | The percentage of unstable lesions as defined by the core lab OCT core lab that were not defined as potential culprit lesion by the investigators after conventional angiography. This will reflect the incidence of undiagnosed and untreated coronary culprit coronary lesion after OHCA. | Intra operative, up to 12 months | 
| The percentage of stable lesions (core lab OCT) intended to be treated by PCI after peri procedural (as assessed by investigators) conventional angiography | A stable lesion will be defined as a coronary stenosis ≥20% without any features of instability (no plaque rupture or erosion, no thrombosis) on core-lab OCT. | Intra operative, up to 12 months | 
| The percentage of misclassification for unstable lesion between peri procedural (as assessed by investigators) OCT and core lab OCT analysis. | The unstable lesion as detected during the procedure by the investigator and compared with the corelab analysis. | Intra operative, up to 12 months | 
| The duration of the procedure | Duration on the procedure will include timing from arterial sheath insertion to final run of angiography (angio), to final run of OCT (intracoronary imaging), and from the end of the angiography or intra coronary imaging to the end of the PCI procedure when applicable (Usually between set puncture to introducer removal). | Intra operative, up to 12 months | 
| The irradiation during the procedure | Patient irradiation will be determined after conventional angiography (angio), after OCT procedure (intracoronary imaging), and after PCI when applicable (angioplasty). Total procedural irradiation will also be calculated as the cumulative irradiation received during angio, intracoronary imaging and PCI if applicable. | Intra operative, up to 12 months | 
| The volume of contrast dye injection | The volume of contrast dye injection will be determined after conventional angiography (angio), after OCT procedure (intracoronary imaging), and after PCI when applicable (angioplasty). Total volume of contrast dye injection will also be calculated as the cumulative volume injected during angio, intracoronary imaging and PCI when applicable | Intra operative, up to 12 months | 
| The rate of OCT-related complications | The OCT related complications include coronary dissection, perforation, plaque embolization etc. | Intra operative, up to 12 months | 
| The rate of Major Adverse Coronary and Cerebrovascular Events (MACCE). | The MACCE evaluation will include all-cause mortality, myocardial infarction, stroke, ischemia driven target lesion revascularization. | Day 1, Day 30 and Day 90 | 
| The rate of all-cause mortality | This includes all cause mortality rate | Day 1, Day 30, Day 90 and Day 365 | 
| The rate of stent thrombosis | According to Academic Research Consortium-2 (ARC2) definition | Day 1, Day 30 and Day 90 |