Diagnostic Accuracy of ECG-less Gated Cardiac CT in Resuscitated Cardiac Arrest Survivors
Phase: NA
Conditions: Cardiac Arrest (CA), Myocardial Infarction (MI)
Sponsor: Universitair Ziekenhuis Brussel

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Study Protocol - Interventional study 
with product or medical device 
 
Study Title: "Diagnostic Accuracy of ECG-less gated Cardiac CT in Resuscitated Cardiac Arrest 
survivors" 
 
Study Acronym: "Optimizing Post-Arrest Evaluation with ECG-less gated Cardiac CT"  (OPEN CCT 
Arrest) 
 
Protocol Version and Date: 
Version 1, March 4
th 2025. 
 
Registry Number: /  
 
Investigational Product or Medical Device: Revolution Apex Elite Computed Tomogrphy Scanning 
Systems, GE Medical Systems LLC 
 
 
 
 
 
 
 
 
 
Sponsor: UZ Brussel 
 
 
 
Coordinating/Principal Investigator: Bert Popelier 
 
 
Study Start Date: 01-06-2025 
 
Expected Study End Date*: 31-05-2027 
 
*In case of extension of study end date à a new date must be submitted to the EC via an amendment and the insurance 
department must be notified regarding the extension. 
 
 
The information contained in this document is the property of the Sponsor/Coordinating 
Investigator and may not be reproduced, published or disclosed to others without written 
authorization of the Sponsor/Coordinating Investigator. 
 
 
 
 

 
 
 
 
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PROTOCOL SIGNATURE PAGE 
 
 
I agree: 
- 
to assume responsibility for the proper conduct of this study 
- 
to conduct the study in compliance with this protocol and any future amendments  
- 
not to implement any deviations from or changes to the protocol without prior review 
and written approval from the Ethics Committee, except where necessary to eliminate an 
immediate hazard to the subjects, or for administrative aspects of the study (where 
permitted by all applicable regulatory requirements) 
- 
that I am thoroughly familiar with the appropriate use of the investigational drug/medical 
device, as described in this protocol 
- 
to ensure that all persons assisting me with the study are adequately informed about the 
investigational drug/medical device and their study-related duties and functions as 
described in the protocol 
- 
that I am aware of and will comply with the current good clinical practice (GCP) guidelines 
and ethical principles outlined in the Declaration of Helsinki 
- 
to conduct the study in accordance with all applicable laws and regulations 
 
 
 
 
 
 
Printed name                                                      Signature                                         Date 
Bert Popelier  
 
 
 
 
 
 
 
 
March 4
th  2025

 
 
 
 
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Table of Contents 
1 
Sponsor/Coordinating Investigator Information ..................................................................... 4 
2 
List of Abbreviations ............................................................................................................. 4 
3 
Protocol Version History ........................................................................................................ 5 
4 
Trial Registration/Protocol Summary ..................................................................................... 6 
5 
Background and Rationale ..................................................................................................... 7 
5.1 
Overview of Disease Pathogenesis with Relevant Literature . Fout! Bladwijzer niet gedefinieerd. 
5.2 
Epidemiology ...................................................................... Fout! Bladwijzer niet gedefinieerd. 
5.3 
Current Treatments ............................................................ Fout! Bladwijzer niet gedefinieerd. 
5.4 
Study Rationale ................................................................... Fout! Bladwijzer niet gedefinieerd. 
5.5 
Rationale for Study Design .................................................. Fout! Bladwijzer niet gedefinieerd. 
5.6 
Rationale for Dose and Regimen ......................................... Fout! Bladwijzer niet gedefinieerd. 
6 
Study Objectives and Endpoints ............................................................................................. 9 
6.1 
Primary Objectives ........................................................................................................ 9 
6.2 
Secondary Objectives ..................................................................................................... 9 
6.3 
Endpoints ...................................................................................................................... 9 
7 
Research Methods ................................................................................................................. 9 
7.1 
Study Design ................................................................................................................. 9 
7.2 
Study Population ............................................................................................................ 9 
7.2.1 Inclusion Criteria ........................................................................................................ 9 
7.2.2 Exclusion Criteria ....................................................................................................... 9 
7.2.3 Contraception / Pregnancy Avoidance Measures ...................................................... 10 
7.3 
Study Duration for Subjects ......................................................................................... 10 
7.4 
Group Allocation & Blinding (if applicable) ................................................................... 10 
8 
Study Assessments and Procedures ..................................................................................... 11 
8.1 
Schedule of Activities ................................................................................................... 11 
8.2 
Study Assessments/Interventions per Visit .......................... Fout! Bladwijzer niet gedefinieerd. 
8.2.1 Screening ................................................................................................................. 14 
8.2.2 Treatment Period .......................................................... Fout! Bladwijzer niet gedefinieerd. 
8.2.3 Follow Up Period ...................................................................................................... 14 
8.2.4 End of Study Visit .......................................................... Fout! Bladwijzer niet gedefinieerd. 
8.3 
Detailed Study Assessments ......................................................................................... 14 
8.3.1 Physical Examination ..................................................... Fout! Bladwijzer niet gedefinieerd. 
8.3.2 Vitals Signs ................................................................... Fout! Bladwijzer niet gedefinieerd. 
8.3.3 Laboratory Testings ................................................................................................. 14 
8.3.4 Efficacy Assessments .................................................... Fout! Bladwijzer niet gedefinieerd. 
8.3.5 Safety Assessments .................................................................................................. 14 
9 
Interventions/Treatment ...................................................................................................... 15 
9.1 
Treatments Administered ............................................................................................ 15 
9.2 
Product/Device Characteristics .................................................................................... 15 
9.3 
Storage, Packaging and Labelling ....................................... Fout! Bladwijzer niet gedefinieerd. 
9.4 
Dosing Regimen .................................................................. Fout! Bladwijzer niet gedefinieerd. 
9.4.1 Dose Administration ..................................................... Fout! Bladwijzer niet gedefinieerd. 
9.4.2 Dose Modifications and Dose Delay ............................... Fout! Bladwijzer niet gedefinieerd. 

 
 
 
 
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9.4.3 Treatment Interruption and Treatment Discontinuation . Fout! Bladwijzer niet gedefinieerd. 
9.5 
Treatment Compliance & Accountability .............................. Fout! Bladwijzer niet gedefinieerd. 
9.6 
Blinding & Unblinding Procedures ....................................... Fout! Bladwijzer niet gedefinieerd. 
9.7 
Concomitant Treatment ...................................................... Fout! Bladwijzer niet gedefinieerd. 
9.8 
Prohibited Treatment .......................................................... Fout! Bladwijzer niet gedefinieerd. 
9.9 
Known Interactions with Other Drugs ................................. Fout! Bladwijzer niet gedefinieerd. 
9.10 
Known Undesirable Effects of Study Drug ............................ Fout! Bladwijzer niet gedefinieerd. 
9.11 
Study Drug Disposal and Destruction .................................. Fout! Bladwijzer niet gedefinieerd. 
10 Data Collection and Management ........................................................................................ 16 
10.1 
Monitoring ................................................................................................................... 16 
10.1.1 
Composition of a Data Monitoring Committee (if applicable) ........ Fout! Bladwijzer niet 
gedefinieerd. 
10.2 
Data Collection ............................................................................................................ 16 
10.3 
Database Management and Quality Control ................................................................. 16 
11 Safety Monitoring and Reporting ......................................................................................... 16 
11.1 Adverse Events ................................................................................................................ 16 
11.1.1 
Definitions ........................................................................................................... 16 
11.1.2 
Reporting ............................................................................................................. 16 
11.1.3 
Laboratory Test Abnormalities ............................................................................. 16 
11.2 
Serious Adverse Events ................................................................................................ 16 
11.2.1 
Definitions ........................................................................................................... 16 
11.2.2 
Immediate Reporting ............................................................................................ 17 
11.3 
Suspected Unexpected Serious Adverse Reactions (SUSAR) ............................................ 17 
11.3.1 
Definitions ........................................................................................................... 17 
11.3.2 
Immediate Reporting ................................................. Fout! Bladwijzer niet gedefinieerd. 
11.4 
Device Deficiencies ....................................................................................................... 17 
11.4.1 
Definitions ........................................................................................................... 17 
11.4.2 
Immediate Reporting ................................................. Fout! Bladwijzer niet gedefinieerd. 
11.5 
Procedures for Handling Special Situations ......................... Fout! Bladwijzer niet gedefinieerd. 
11.5.1 
Overdose Management .............................................. Fout! Bladwijzer niet gedefinieerd. 
11.5.2 
Pregnancy ................................................................. Fout! Bladwijzer niet gedefinieerd. 
11.6 
Annual Safety Report .......................................................... Fout! Bladwijzer niet gedefinieerd. 
12 Ethical Considerations ......................................................................................................... 18 
12.1 
Ethical Conduct of the Study ........................................................................................ 18 
12.1.1 
Declaration of Helsinki ......................................................................................... 18 
12.1.2 
Ethics Committee ................................................................................................. 18 
12.2 
Recruitment and Informed Consent .............................................................................. 18 
12.3 
Study Data Protection .................................................................................................. 18 
12.4 
Subject Identification ................................................................................................... 18 
13 Insurance ............................................................................................................................ 18 
14 Reporting and Dissemination .............................................................................................. 18 
15 Finance and Conflict of Interest Statement ................................ Fout! Bladwijzer niet gedefinieerd. 
16 Tables and Figures ................................................................... Fout! Bladwijzer niet gedefinieerd. 
17 References .......................................................................................................................... 19 
 
 
 

 
 
 
 
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1 Sponsor/Coordinating Investigator Information 
Sponsor: 
UZ Brussel 
 
Principal Investigator: 
Bert Popelier 
 
Subinvestigator(s): 
Stijn Lochy 
 
Statistician: 
Andreea Iulia Motoc 
 
2 List of Abbreviations 
 
ACS  
Acute Coronary Syndrome 
AE 
 
Adverse Event 
AR 
 
Adverse Reaction 
ATMP 
Advanced Therapy Medicinal Product 
AxMP  
Auxiliary Medicinal Product 
CABG  
Coronary Artery Bypass Graft 
CA 
 
Competent Authority 
CCTA  
Cardiac Computed Tomography Angiography 
CRA  
Clinical Research Associate 
CRF  
Case Report Form 
CRO  
Contract Research Organisation 
CPC  
Cerebral Performance Category 
CPR  
Cardiopulmonary Resuscitation 
CT 
 
Clinical Trial 
CTA  
Clinical Trial Authorisation 
CTIS  
Clinical Trial Information System 
CTR   
Clinical Trial Regulation 
DAPT  
 
Dual Antiplatelet Therapy 
DSMB  
Data Safety Monitoring Board 
EC  
 
Ethics Committee 
ECPR  
Extracorporeal Cardiopulmonary Resuscitation 
e-CRF  
Electronic Case Report Form 
EMA   
European Medicines Agency 
EU  
 
European Union 
FANC  
Federal Agency for Nuclear Control 
GCP   
Good Clinical Practice 
GDPR  
General Data Protection Regulation 
IB  
 
Investigator’s Brochure 
IC  
 
Informed Consent 
ICF   
Informed Consent Form 

 
 
 
 
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ICH   
International Conference on Harmonisation 
ICA   
Invasive Coronary Angiography 
IHCA   
In-Hospital Cardiac Arrest 
IMP   
Investigational Medicinal Product 
IMPD  
Investigational Medicinal Product Dossier 
IVUS   
Intravascular Ultrasound 
MCS   
Mechanical Circulatory Support 
MS  
 
Member State 
NSTEMI  
Non-ST Elevation Myocardial Infarction 
OCT   
Optical Coherence Tomography 
OHCA  
Out-of-Hospital Cardiac Arrest 
PCI   
Percutaneous Coronary Intervention 
PI  
 
Principal Investigator 
ROSC  
Return of Spontaneous Circulation 
RSI   
Reference Safety Information 
SAE   
Serious Adverse Event 
SAR   
Serious Adverse Reaction 
SmPC  
 
Summary of Product Characteristics 
SOP   
Standard Operating Procedure 
STEMI  
ST Elevation Myocardial Infarction 
SUSAR  
Suspected Unexpected Serious Adverse Reaction 
VA-ECMO  Veno-Arterial Extracorporeal Membrane Oxygenation 
 
 
3 Protocol Version History 
 
Version N
O  
Version Date 
Summary of changes 
1 
March 4
th 2025 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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4 Trial Registration/Protocol Summary 
Information 
Objectives: 
Investigate the feasibility and diagnostic accuracy of ECG-less gated CCTA in 
cardiac arrest survivors without STEMI, by means of agreement with ICA.  
 
Study 
population: 
Cardiac arrest survivors without STEMI. 
In- 
and 
exclusion 
criteria: 
 
 
- 
Inclusion:  
o 
Adults (≥18 years) with sustained return of spontaneous circulation (ROSC) 
following in/out-of-hospital cardiac arrest. 
o 
Informed consent from patient or representative obtained before invasive 
coronary angiography. 
 
- 
Exclusion 
o 
Patients on VA-ECMO 
o 
ACS STEMI or STEMI “equivalent” 
§ 
New left/right bundle branch block 
§ 
ST segment depression in leads V1-V3, when the terminal T wave is 
positive and concomitant ST-segment elevation ≥ 0,5mm recorded in 
leads V7-V9 (posterior MI) 
§ 
ST-segment elevation in V7-V9 (posterior MI) or V3R-V4R (RV MI) 
o 
ACS NSTEMI with persistent ST depression despite optimal therapy, 
suggesting ongoing myocardial ischemia, with indication for an urgent ICA 
according to the treating physician. 
o 
Hemodynamic/electrical instability precluding CT imaging (as perceived by 
the treating physician) 
o 
Life-threatening arrhythmia potentially caused by acute myocardial ischemia 
o 
Absolute contraindications to iodinated contrast 
o 
Patients with a known non-cardiac cause of cardiac arrest (e.g., traumatic 
brain injury, overt hemorrhage, asphyxia/severe hypoxia due to known lung 
disease, trauma, severe metabolic/electrolyte derangement, or intoxication) 
as perceived by the treating physician, where chest CT is considered 
unnecessary. 
o 
Known or likely pregnancy or lactation 
o 
Severe bleeding issue (as perceived by the treating physician) precluding 
heparin administration during radial access coronary angiography.  
o 
Prior coronary intervention (stent implantation/CABG). 
o 
CT findings indicating a condition that precludes coronary angiography in 
the short term.  
o 
Patients with end-of-life care pathways. 
o 
Participation in another intervention study interfering with the research 
questions in OPEN CCT Arrest. 
 
Factors 
of 
interest / Data 
to be collected: 
Chest CT scan (as early as possible) + CT brain (+ CT abdomen if perceived indicated 
by the treating physician) 
Pulmonary embolism/aortic dissection protocol 
ECG-less gated CCTA 
Invasive coronary angiography (<24 hours after CT scan) 
Registration of baseline characteristics at admission 
Registration of in study related parameters 
Assessment of 90 days outcome 

 
 
 
 
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Assessment of agreement between ECG-less CCTA and ICA 
 
 
 
Endpoints: 
Primary endpoint will be the percentage of patients correctly 
classified to coronary artery disease as the cause of cardiac arrest 
after the CT scan.  
 
Secondary endpoints 
- 
level of agreement between CCTA and ICA based evaluation of 
the degree of coronary stenosis. 
- 
Feasibility: data on coronary stenosis based on ECG-less CCTA 
cannot be provided or is incompletely provided. 
- 
Reasons for failure of complete CCTA reporting. 
- 
Clinical outcomes at 90 days. 
 
Target sample 
size: 
30 patients 
 
 
 
 
Statistical 
considerations: 
We will make use of descriptive statistics. The level of agreement will be assessed 
with the Weighted Kappa coefficient. 
 
 
 
5 Background and Rationale 
5.1 
Overview of Relevant Literature 
 
Acute coronary syndrome (ACS) is the most important treatable cause of cardiac arrest. In contrast 
with cardiac arrest survivors with ST elevation myocardial infarction (STEMI), current guidelines do 
not recommend unselected/routine urgent invasive coronary angiography (ICA) in the patients with 
cardiac arrest without STEMI
1. This recommendation reflects existing evidence indicating that 
immediate invasive strategies may not confer significant benefit in this population and may even be 
harmful
2, 3 4, while another ongoing randomized controlled trial is investigating this
5.  Nevertheless, 
in COACT
2, a landmark trial investigating a strategy of immediate versus delayed coronary 
angiography in out-of-hospital cardiac arrest patients without STEMI, one or more culprit coronary 
lesions responsible for triggering cardiac arrest were identified in 40% of the total patient 
population. The question remains pertinent whether well selected cardiac arrest survivors without 
STEMI can benefit from early ICA. Yet, current available clinical tools fail to identify these patients. 
Markers such as clinical history, echocardiographic abnormalities, arrest rhythm (shockable/non-
shockable), ECG changes other than ST-segment elevation and troponin levels lack sufficient 
sensitivity and specificity in a cardiac arrest setting for predicting ACS requiring intervention
6, 7, 8, 9, 10, 
11. 
The diagnostic value of ECG-gated cardiac computed tomography angiography (CCTA) for detection 
of both acute and chronic coronary artery syndrome is well established
12, 13, with recent evidence 
demonstrating the additional value of fractional flow reserve (FFR)-CT in ACS
14. Nonetheless, the 

 
 
 
 
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need for ECG-gating remains a limitation.  
Recently an ECG-less CCTA modality was developed, but its diagnostic accuracy is still under 
validation
15. ECG-less cardiac or coronary  CT angiography  (CCTA) allows cardiac imaging without 
requiring an ECG signal from the patient. Thus, it eliminates the steps associated with using a 
patient-attached ECG monitor: skin preparation, attaching the ECG leads, checking impedance, and 
confirming that the leads provide an adequate ECG signal to the scanning system. Therefore, 
workflow is optimized, which is critical in an emergency setting. In situations where it is difficult to 
attach the ECG leads, such as patients in a resuscitation setting who already have diagnostic ECG 
leads in place or other instrumentation, it is also advantageous that there is no need for an ECG 
signal. 
Cardiac arrest patients without STEMI and with no evident non-cardiac cause generally undergo CT 
imaging of head and chest for evaluation of potential causes of cardiac arrest (e.g. pulmonary 
embolism, acute aortic dissection, intracranial hemorrhage). While ECG-gated CCTA is considered 
the optimal modality for non-invasive coronary imaging, ECG-less CCTA might offer a highly 
interesting alternative with the advantages mentioned earlier. Other benefits include no substantially 
longer scanning time, no need for additional contrast injection or administration of betablockers.  
In case the technique is well validated, future clinical questions could include whether ECG-less CCTA 
can help to identify a patient population of cardiac arrest survivors without STEMI that do benefit 
from early invasive coronary angiography and whether earlier treatment could improve outcome. 
 
5.2 
Study Rationale and Purpose 
This study aims to investigate the feasibility and diagnostic accuracy of ECG-less gated CCTA in 
cardiac arrest survivors without STEMI, by means of agreement with ICA.  
 
 
 
 

 
 
 
 
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6 Study Objectives and Endpoints 
6.1  
Primary Objectives 
 
Investigate the feasibility and diagnostic accuracy of ECG-less gated CCTA in cardiac arrest 
survivors without STEMI, by means of agreement with ICA.  
 
6.2  
Secondary Objectives 
- 
level of agreement between CCTA and ICA based evaluation of the degree of coronary 
stenosis. 
- 
Feasibility: data on coronary stenosis based on ECG-less CCTA cannot be provided or is 
incompletely provided. 
- 
Reasons for failure of complete CCTA reporting. 
- 
Clinical outcomes at 90 days. 
6.3 
Endpoints 
Primary endpoint  
- 
Percentage of patients correctly classified to coronary artery disease as the cause of cardiac 
arrest after the CT scan.  
 
Secondary endpoints 
- 
level of agreement between CCTA and ICA based evaluation of the degree of coronary 
stenosis. 
- 
Feasibility: data on coronary stenosis based on ECG-less CCTA cannot be provided or is 
incompletely provided. 
- 
Reasons for failure of complete CCTA reporting. 
- 
Clinical outcomes at 90 days. 
 
7 Research Methods 
7.1 
Study Design 
Single-center, prospective, non randomized, interventional study. 
7.2 
Study Population 
7.2.1 
Inclusion Criteria  
o 
Adults (≥18 years) with sustained return of spontaneous circulation (ROSC) following in/out-
of-hospital cardiac arrest. 
o 
Informed consent from patient or representative obtained before invasive coronary 
angiography. 
7.2.2 
Exclusion Criteria 
o 
Patients on VA-ECMO 
o 
ACS STEMI or STEMI “equivalent” 
§ 
New left/right bundle branch block 
§ 
ST segment depression in leads V1-V3, when the terminal T wave is positive and 
concomitant ST-segment elevation ≥ 0,5mm recorded in leads V7-V9 (posterior MI) 
§ 
ST-segment elevation in V7-V9 (posterior MI) or V3R-V4R (RV MI) 
o 
ACS NSTEMI with persistent ST depression despite optimal therapy, suggesting ongoing 
myocardial ischemia, with indication for an urgent ICA according to the treating physician. 
o 
Hemodynamic/electrical instability precluding CT imaging (as perceived by the treating 
physician) 
o 
Life-threatening arrhythmia potentially caused by acute myocardial ischemia 
o 
Absolute contraindications to iodinated contrast 
o 
Patients with a known non-cardiac cause of cardiac arrest (e.g., traumatic brain injury, overt 
hemorrhage, asphyxia/severe hypoxia due to known lung disease, trauma, severe 

 
 
 
 
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metabolic/electrolyte derangement, or intoxication) as perceived by the treating physician, 
where chest CT is considered unnecessary. 
o 
Known or likely pregnancy or lactation 
o 
Severe bleeding issue (as perceived by the treating physician) precluding heparin 
administration during radial access coronary angiography.  
o 
Prior coronary intervention (stent implantation/CABG). 
o 
CT findings indicating a condition that precludes coronary angiography in the short term.  
o 
Patients with end-of-life care pathways. 
o 
Participation in another intervention study interfering with the research questions in OPEN 
CCT Arrest. 
7.2.3 
Contraception / Pregnancy Avoidance Measures 
Pregnant women will be excluded.  
7.3 
Study Duration for Subjects 
90 days.  
7.4 
Group Allocation & Blinding (if applicable) 
Not applicable. 
 
 

 
 
 
 
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8 Study Assessments and Procedures 
8.1 
Schedule of Activities 
Chest CT scan (as early as possible) 
 + CT brain (+ CT abdomen if perceived indicated by the treating physician) 
Pulmonary embolism/aortic dissection protocol 
ECG-less gated CCTA (1) 
 
 
Standard of care 
Study-specific 
Invasive coronary angiography (<24 hours after CT scan) 
Standard of care 
Registration of baseline characteristics at admission (2) 
Standard of care 
Registration of study related parameters (3) 
Study specific 
Assessment of 90 days outcome (4) 
Study-specific 
Assessment of agreement between ECG-less CCTA and ICA (5) 
Study-specific 
 
ECG-less gated CCTA 
ECG-less Cardiac software is an FDA-approved cardiac scan mode that acquires cardiac images 
without the need of a patient-attached ECG monitor. ECG-less Cardiac essentially utilizes existing 
CT system scan technology. The system uses a wide detector coverage of 160mm to provide full 
heart coverage and a fast gantry speed of 0.23 seconds per rotation to perform imaging in a single 
cardiac cycle. An estimate of the heart rhythm has to be provided, which is often readily available 
because emergency patients are already monitored. Based on the heart rhythm the scanner 
simulates an ECG signal. This simulated ECG signal provides virtual gating of the scan. The 
acquisition can be performed during a full heart cycle or three-quarters or half cycle, depending on 
how fast the heart rhythm is. The existing cardiac software options of SmartPhase (automated phase 
selection) and SnapShot Freeze 2 (optimized volume registration) amplify the quality of the images 
and correct for motion. 
Patients are scanned using a Revolution Apex Elite system (GE Healthcare, Waukesha, WI -USA). We 
use a hyperdrive pulmonary CT angiography (523mm/s with 0.28s/rotation gantry speed). After a 
short delay of a few seconds (5-12 sec), allowing the contrast to leave the pulmonary circulation, 
and enter the aorta and coronary arteries, a coronary CT angiography is performed within the same 
contrast bolus. No extra contrast is given to acquire the cardiac images. No intravenous beta-blocker 
nor 
sublingual 
nitroglycerin 
is 
administered. 
The total added exam time (assessing heart rhythm, preparing the scan parameters, the delay time 
and 
the 
acquisition 
itself) 
is 
about 
one 
to 
two 
minutes. 
The dose-length product (DLP) of the ECG-less cardiac scan depends on the duration of the scan 
time that is chosen. The average DLP is between 150 and 200 mGy.cm. The diagnostic reference 
level (DRL) as set by the Federal Agency for Nuclear Controle (FANC) for a coronary CT angiography 
is 300 mGy.cm.  
The combined pulmonary CT angiography and ECG-less cardiac scan can be used to diagnose all the 
pathologies that can be assessed on a conventional pulmonary CT angiography scan (including, but 
not limited to, pneumonia, pleural fluid, pulmonary embolism, pulmonary infarct, pulmonary mass, 
pneumothorax, pericardial fluid, etc.) and provides extra diagnostic information about coronary 
artery disease. 
 
 

 
 
 
 
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Baseline characteristics of the study population. 
Age 
Sex category 
BMI 
Medical conditions / cardiovascular risk factors 
Diabetes mellitus 
Arterial hypertension 
Current smoker 
Dyslipidemia 
Peripheral artery disease 
Previous stroke / Transient Ischemic Attack (TIA) 
Clinical observations during cardiorespiratory arrest 
Cardiac arrest witnessed 
Shockable first monitored rhythm  
Bystander CPR 
No flow time 
Low flow time 
Median time from cardiac arrest to ROSC 
After hospital admission 
First arterial pH 
First arterial lactate level 
First troponin T level 
First creatinine level 
Vasoactive drug(s) (Y/N) 
 

 
 
 
 
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(1) Study related parameters 
- 
Median time from cardiac arrest to ECG-less gated CCTA 
- 
Median time from cardiac arrest to ICA 
- 
Catheterization access 
o Femoral 
o Radial 
o Brachial 
- 
Culprit lesion identified 
- 
Patients with coronary artery disease without a culprit lesion 
- 
Use of intravascular imaging (OCT/IVUS) (Y/N) 
- 
PCI performed  
- 
Median amount of contrast dye (CT scan) 
- 
Median amount of contrast dye (coronary angiography) 
- 
Total radiation dose (mSv) 
- 
Time-to-diagnosis of ACS as a cause of cardiac arrest 
- 
Time-to-diagnosis of a non-cardiac cause of cardiac arrest 
o Pulmonary embolism 
o Intracranial hemorrhage 
o Acute aortic dissection 
o Other 
- 
Feasibility (patients meeting inclusion criteria where ECG-less CCTA with 
sufficient quality was obtained) 
 
(2) Outcome at 90 days 
- 
Survival (Y/N) 
- 
severe neurologic deficit (≥ 3) (Y/N) 
- 
Median peak troponin release  
- 
Median length of ICU stay (days) 
- 
Median duration of catecholamine support (days) 
- 
Median peak SAPS II score 
- 
Rehospitalization for heart failure (Y/N) 
- 
Acute kidney injury (Y/N) 
- 
Need for renal replacement therapy (Y/N) 
- 
ISTH major bleeding event 
- 
Ischemic stroke 
- 
Need for mechanical circulatory support (MCS) 
- 
Treatment with Dual Antiplatelet Therapy (DAPT) 
- 
LV function on 90 days ambulatory follow-up visit 
 
 
 

 
 
 
 
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(3) Assessment of agreement between CCTA and ICA  
Degree of coronary stenosis is divided into 3 categories (0, <50%, ≥50%) for every 
coronary segment. Angiographic and CT images are respectively evaluated by the 
consensus of two interventional cardiologists (ICA) and two interventional 
radiologists (CCTA), blinded for clinical data. In case of discrepant results between 
the two readers of the same imaging modality, a third reader will provide the 
deciding assessment.  
The level of agreement will be assessed with the Weighted Kappa coefficient. 
  
8.1.1 
Screening 
Screening will be performed by the treating physician in every cardiac arrest 
patient at the moment of ROSC.  
8.1.2 
Follow Up Period 
Clinical data, mentioned above, will be collected at 90 days after inclusion by 
interrogation of the clinical data system (Primuz). 
8.2 
Detailed Study Assessments 
8.2.1 
Laboratory Testings 
First arterial lactate and pH, venous creatinine and troponin T level. 
8.2.2 
Safety Assessments 
Registration of contrast dye volume (for both CT and ICA), total radiation dose. 
 
 

 
 
 
 
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9 Interventions/Treatment 
9.1 
Treatments Administered 
Standard of care for the treatment of cardiac arrest survivors will be administered. 
9.2 
Product/Device Characteristics 
ECG-less Cardiac software is an FDA-approved cardiac scan mode that acquires 
cardiac images without the need of a patient-attached ECG monitor. ECG-less 
Cardiac essentially utilizes existing CT system scan technology. The system uses a 
wide detector coverage of 160mm to provide full heart coverage and a fast gantry 
speed of 0.23 seconds per rotation to perform imaging in a single cardiac cycle. 
An estimate of the heart rhythm has to be provided, which is often readily 
available because emergency patients are already monitored. Based on the heart 
rhythm the scanner simulates an ECG signal. This simulated ECG signal provides 
virtual gating of the scan. The acquisition can be performed during a full heart 
cycle or three-quarters or half cycle, depending on how fast the heart rhythm is. 
The existing cardiac software options of SmartPhase (automated phase selection) 
and SnapShot Freeze 2 (optimized volume registration) amplify the quality of the 
images and correct for motion. 
Patients are scanned using a Revolution Apex Elite system (GE Healthcare, 
Waukesha, WI -USA). We use a hyperdrive pulmonary CT angiography (523mm/s 
with 0.28s/rotation gantry speed). After a short delay of a few seconds (5-12 sec), 
allowing the contrast to leave the pulmonary circulation, and enter the aorta and 
coronary arteries, a coronary CT angiography is performed within the same 
contrast bolus. No extra contrast is given to acquire the cardiac images. No 
intravenous beta-blocker nor sublingual nitroglycerin is administered. 
The total added exam time (assessing heart rhythm, preparing the scan 
parameters, the delay time and the acquisition itself) is about one to two minutes. 
The dose-length product (DLP) of the ECG-less cardiac scan depends on the 
duration of the scan time that is chosen. The average DLP is between 150 and 200 
mGy.cm. The diagnostic reference level (DRL) as set by the Federal Agency for 
Nuclear Control (FANC) for a coronary CT angiography is 300 mGy.cm.  
The combined pulmonary CT angiography and ECG-less cardiac scan can be used 
to diagnose all the pathologies that can be assessed on a conventional pulmonary 
CT angiography scan (including, but not limited to, pneumonia, pleural fluid, 
pulmonary embolism, pulmonary infarct, pulmonary mass, pneumothorax, 
pericardial fluid, etc.) and provides extra diagnostic information about coronary 
artery disease. 
 
 
 

 
 
 
 
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10 Data Collection and Management 
10.1 
Monitoring  
The investigator must make all trial documentation and related records available in case a 
monitoring visit is requested. Also in case of regulatory inspections all trial documentation should 
be made available to the inspector(s). All participant data must be handled and treated 
confidentially. 
 
10.2 
Data Collection 
An Electronic Data Capture system “RedCap” will be used for data collection. Trial data will be entered 
within 
reasonable 
time 
after 
the 
subject 
underwent 
the 
necessary 
investigations. 
Corrections/modifications will be automatically tracked by an audit trail detailing date and time of 
the correction and the name of person performing the correction. 
 
10.3 
Database Management and Quality Control  
Degree of coronary stenosis is divided into 3 categories (0, <50%, ≥50%) for every 
coronary segment. Angiographic and CT images are respectively evaluated by the 
consensus of two interventional cardiologists (ICA) and two interventional 
radiologists (CCTA), blinded for clinical data. In case of discrepant results between 
the two readers of the same imaging modality, a third reader will provide the 
deciding assessment.  
The final conclusion on whether or not the cause of the cardiac arrest is related to 
the CAD, will be made by the interventional cardiologist performing the ICA, 
taking into account the clinical context, ECG findings, angiographic data and 
intracoronary imaging in case of doubt.  
The level of agreement on the grade of coronary stenosis between CCTA and ICA 
will be assessed with the Weighted Kappa coefficient. 
 
11 Safety Monitoring and Reporting 
11.1 Adverse Events  
11.1.1 
Definitions 
An adverse event is any untoward medical occurrence, unintended disease or injury or any untoward 
clinical signs, including an abnormal laboratory finding, in subjects, users or other persons in the 
context of  a clinical investigation, whether or not related to the investigational device. 
Note: 
a) This definition includes events that are anticipated as well as unanticipated events 
b) This definition includes events occurring in the context of  a clinical investigation related to 
the investigational device, the comparator or the procedures involved 
11.1.2 
Reporting  
Adverse events will be reported based on the analysis of the clinical patient file.   
11.1.3 
Laboratory Test Abnormalities 
Follow-up of renal function will be documented. 
11.2 
Serious Adverse Events  
11.2.1 
Definitions  
Any adverse event that led to any of the following: 
a) Death, 
b) Serious deterioration in the health of the subject, that resulted in any of the following: 

 
 
 
 
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• 
Life-threatening illness or injury, 
• 
Permanent impairment of a body structure or a body function, 
• 
Hospitalization or prolongation of patient hospitalization, 
• 
Medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment of a body structure or a body function, 
• 
Chronic disease 
c) Foetal distress, foetal death or a congenital physical or mental impairment or birth defect. 
 
Medical and scientific judgement should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately life-
threatening or result in death or hospitalisation but may jeopardise the patient or may require 
intervention to prevent one of the other outcomes listed in the definition above. These should also 
be considered serious. 
 
11.2.2 
Immediate Reporting  
11.3 
Suspected Unexpected Serious Adverse Reactions (SUSAR) 
11.3.1 
Definitions 
An adverse reaction is any untoward medical occurrence in a patient or clinical investigation subject 
participating in a clinical trial including any abnormal sign, symptom, or disease temporally 
associated with the participant’s involvement in the research, whether or not considered to be 
related to the research. 
 
Serious if:  
• 
Results in death, 
• 
Is life-threatening, 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization, 
• 
Results in persistent or significant disability/incapacity, 
• 
Is a congenital anomaly/birth defect 
Or 
• 
Other important medical condition (ICH 2EA) 
 
Medical and scientific judgement should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately life-
threatening or result in death or hospitalisation but may jeopardise the patient or may require 
intervention to prevent one of the other outcomes listed in the definition above. These should also 
be considered serious. 
11.4 
Device Deficiencies 
11.4.1 
Definitions 
Any inadequacy in the identity, quality, durability, reliability, safety or performance of an 
investigational device, including malfunction, user errors or inadequacy in information supplied by 
the manufacturer. 
 
 

 
 
 
 
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12 Ethical Considerations 
12.1 
Ethical Conduct of the Study 
12.1.1 
Declaration of Helsinki 
The trial will be performed in accordance with the Declaration of Helsinki, the conditions and 
principles of Good Clinical Practice, the protocol and applicable local regulatory requirements and 
laws. 
12.1.2 
Ethics Committee 
Before the start of the trial or implementation of any amendment, approval of the trial protocol and 
amendments, informed consent forms and other relevant documents will be obtained from the 
applicable ethical committee(s). 
12.2 
Recruitment and Informed Consent 
Recruitment will be done by the treating physician at the moment of ROSC after cardiac arrest. Each 
participant or his/her representative shall provide Informed Consent before performance of the ICA. 
The IC form that is/are used must be approved by reviewing EC and be in a language that the 
participant can read and understand. The ICF should be in accordance with current ICH and GCP 
guidelines and with applicable local regulations. 
 
12.3 
Study Data Protection  
The collection and processing of personal data from participants enrolled in the study will be limited 
to those data that are necessary to fulfill the objectives of this study. These data must be collected 
and processed with adequate precautions to ensure confidentiality and compliance with applicable 
data protection laws and regulations. 
12.4 
Subject Identification  
The participant identification will be treated as confidential and will be filed by the investigator in 
an identification log. This log is kept at the participating site and shall not be copied. In all reports 
and communication the participant shall be identified with a participant study number. 
 
13 Insurance 
UZ Brussel/VUB is, as Sponsor of the trial, responsible for ensuring appropriate general/product 
liability insurance and as required in accordance with applicable laws and regulations, country-
specific liability insurance coverage for claims made by a trial subjects for injury arising from the 
subject’s participation in the trial. 
 
14 Reporting and Dissemination 
The data and information collected during this trial will be reported in a clinical trial report and/or 
a publication in a scientific/medical journal. Reporting of trial results will be performed according 
to local regulations. 
 
For the correct authorship rules we refer to the International Committee of Medical Journal Editors: 
https://www.icmje.org/recommendations/browse/roles-and-responsibilities/defining-the-role-of-
authors-and-contributors.html 
 
 
 

 
 
 
 
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15 References 
1. Zeppenfeld K, Tfelt-Hansen J, de Riva M, Winkel BG, Behr ER, Blom NA, et al. 
2022 ESC Guidelines for the management of patients with ventricular 
arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022 
Oct 21;43(40):3997-4126.  
2. Lemkes JS, Janssens GN, van der Hoeven NW, et al. Coronary angiography 
after cardiac arrest without ST segment elevation (COACT). N Engl J Med. 
2019;380(15):1397–1407. 
3. Desch S, Freund A, Akin I, Behnes M, Preusch MR, Zelniker TA, et al. 
Angiography after out-of-hospital cardiac arrest without ST-segment 
elevation. N Engl J Med. 2021 Dec 30;385(27):2544–53. 
4. Thevathasan T, Freund A, Spoormans E, Lemkes J, Roßberg M, Skurk C, et 
al. Bayesian reanalyses of the trials TOMAHAWK and COACT. JACC 
Cardiovasc Interv. 2024 Dec 23;17(24):2879-2889.  
5. Elfwén L, Lagedal R, Nordberg P, James S, Oldgren J, Böhm F, et al. Direct or 
subacute coronary angiography in out-of-hospital cardiac arrest (DISCO)—
An initial pilot-study of a randomized clinical trial. Resuscitation. 2019 
Jun;139:253-261.  
6. Gonzalez MR, Esposito EC, Leary M, Gaieski DF, Kolansky DM, Chang G, et 
al. Initial clinical predictors of significant coronary lesions after 
resuscitation from cardiac arrest. Ther Hypothermia Temp Manag. 2012 
Jun;2(2):73-7. 
7. Dumas F, Manzo-Silberman S, Fichet J, Mami Z, Zuber B, Vivien B, et al.  Can 
early cardiac troponin I measurement help to predict recent coronary 
occlusion in out-of-hospital cardiac arrest survivors? Crit Care Med. 2012 
Jun;40(6):1777-84. 
8. Lee SE, Uhm JS, Kim JY, Pak HN, Lee MH, Joung B. Combined ECG, 
echocardiographic, and biomarker criteria for diagnosing acute myocardial 
infarction in out-of-hospital cardiac arrest patients. Yonsei Med J. 2015 
Jul;56(4):887-94. 
9. Sideris G, Voicu S, Dillinger JG, Stratiev V, Logeart D, Broche C, et al. Value 
of post-resuscitation electrocardiogram in the diagnosis of acute myocardial 
infarction in out-of-hospital cardiac arrest patients. Resuscitation. 2011 
Sep;82(9):1148-53. 
10.  Stær-Jensen H, Nakstad ER, Fossum E, Mangschau A, Eritsland J, Drægni T, 
et al. Post-resuscitation ECG for selection of patients for immediate 
coronary angiography in out-of-hospital cardiac arrest. Circ Cardiovasc 
Interv. 2015 Oct;8(10):e002784.  
11. Voicu S, Sideris G, Deye N, Dillinger JG, Logeart D, Broche C, et al. Role of 
cardiac troponin in the diagnosis of acute myocardial infarction in 
comatose patients resuscitated from out-of-hospital cardiac arrest. 
Resuscitation. 2012 Apr;83(4):452-8. 
12. Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, et al. 
Diagnostic performance of 64-multidetector row coronary computed 
tomographic angiography for evaluation of coronary artery stenosis in 

 
 
 
 
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individuals without known coronary artery disease: results from the 
prospective multicenter ACCURACY trial. J Am Coll Cardiol. 2008 Nov 
18;52(21):1724-32.  
 
13. Meijboom WB, Meijs MF, Schuijf JD, Cramer MJ, Mollet NR, van Mieghem CA, 
et al. Diagnostic accuracy of 64-slice computed tomography coronary 
angiography: a prospective, multicenter, multivendor study. J Am Coll 
Cardiol. 2008 Dec 16;52(25):2135-44. 
 
14. Meier D, Andreini D, Cosyns B, Skalidis I, Storozhenko T, Mahendiran T, et 
al. Usefulness of FFR-CT to exclude haemodynamically significant lesions in 
high-risk NSTE-ACS. EuroIntervention. 2025 Jan 6;21(1):73-81. 
15. Nabipoorashrafi et al, Cardiac CT angiography without ECG Gating. Journal 
of Cardiovascular Computed Tomography 18 (2024) S1–S98