Effect Of Resuscitative Endovascular Balloon Occlusion of the Aorta in Non-Traumatic Out-of-Hospital Cardiac Arrest (REBOA); A Multinational, Multicenter Randomized Controlled Trial
Phase: NA
Conditions: Cardiopulmonary Arrest
Sponsor: Seoul National University Hospital

 
 
 
 
Study Protocol 
Seoul National University Bundang Hospital 
Far Eastern Memorial Hospital 
Effect Of Resuscitative Endovascular Balloon Occlusion of the Aorta in Non-
Traumatic Out-of-Hospital Cardiac Arrest (REBOA); A Multinational, Multicenter 
Randomized Controlled Trial 
 
 
Trial Registration Number: NCT06031623 
 
Current version number: Version 1.3 
Last updated date: January 24, 2025 
 

Abstract 
Background 
Out-of-hospital cardiac arrest (OHCA) is a significant public health issue worldwide and is 
associated with low survival rates and poor neurological outcomes. The generation of optimal 
coronary perfusion pressure (CPP) via high-quality chest compressions is a key factor in 
enhancing survival rates. However, it is often challenging to provide adequate CPP in real-
world cardiopulmonary resuscitation (CPR) scenarios. Based on animal studies and human 
trials on improving CPP in patients with nontraumatic OHCA, resuscitative endovascular 
balloon occlusion of the aorta (REBOA) is a promising technique in these cases. This study 
aims to investigate the benefits of REBOA adjunct to CPR compared with conventional CPR 
for the clinical management of nontraumatic OHCA. 
 
Methods 
This is a parallel-group, randomized, controlled, multinational trial that will be conducted at 
two urban academic tertiary hospitals in Korea and Taiwan. Patients aged 20–80 years 
presenting with witnessed OHCA will be enrolled in this study. Eligible participants must 
fulfill the inclusion criteria and written informed consent should be collected from their legal 
representatives. Patients will be randomly assigned to the intervention (REBOA-CPR) or 
control (conventional CPR) group. The intervention group will receive REBOA and standard 
advanced cardiovascular life support (ACLS). Meanwhile, the control group will receive ACLS 
based on the 2020 American Heart Association guidelines. The primary outcome is return of 
spontaneous circulation (ROSC). The secondary outcomes include sustained ROSC, survival 
to admission, survival to discharge, neurological outcome, and hemodynamic changes. 

Discussion 
Our upcoming trial can provide essential evidence regarding the efficacy of REBOA, a 
mechanical method for enhancing CPP, in OHCA resuscitation. Our study aims to determine 
whether REBOA can improve treatment strategies for patients with nontraumatic OHCA based 
on clinical outcomes, thereby potentially providing valuable insights, and guiding further 
advancements in this critical public health area. 
 
Trial registration 
ClinicalTrials.gov NCT06031623. Registered on September 9, 2023 
 
Keywords 
cardiac arrest, cardiopulmonary resuscitation, resuscitative endovascular balloon occlusion of 
the aorta, REBOA, out-of-hospital cardiac arrest 
 
 

Administrative information 
Title {1} 
Effect of resuscitative endovascular balloon occlusion of the aorta in nontraumatic out-
of-hospital cardiac arrest: a multinational, multicenter, randomized, controlled trial 
Trial registration {2a and 
2b} 
ClinicalTrials.gov NCT06031623. Registered on September 9, 2023 
Protocol version {3} 
Version 1.3, January 24, 2025 
Funding {4} 
This work is partly supported by a National Research Foundation of Korea grant 
funded by the Korean government (MSIT) (No. NRF-2022R1F1A1074361), the 
Seoul National University Bundang Hospital Research Fund (No. 02-2023-0029), 
and Far Eastern Memorial Hospital (No. PI20230002). 
Name and contact 
information for the trial 
sponsor {5b} 
Professor Dong Keon Lee, Principal Investigator 
Seoul National University College of Medicine 
Seoul National University Bundang Hospital 
Goldenegg@snubh.org 
Role of sponsor {5c} 
This is an investigator initiated trial. The funding source had no role in the design of this 
study and will not have any role during its execution, analyses, interpretation of the data, 
or decision to submit results. 
 
 
 

Introduction 
Background and rationale {6a} 
Out-of-hospital cardiac arrest (OHCA) is a medical emergency that remains a public health 
issue worldwide [1]. The mainstay treatment for cardiac arrest involves immediate attention 
and treatment, including early recognition, high-quality chest compression, early defibrillation 
for shockable rhythm, early epinephrine administration, and immediate advanced airway 
access [2, 3]. With the development of guidelines for the treatment of cardiac arrest, numerous 
efforts have been made worldwide to increase survival rates and improve prognosis in patients 
with OHCA. However, despite such measures, the survival rates of patients with OHCA remain 
<10% in several countries, and the proportion of patients with good neurological prognosis at 
discharge is even lower [1]. 
Cardiopulmonary resuscitation (CPR) for OHCA aims to reduce ischemic damage during 
cardiac arrest via continuous blood flow to the vessels supplying vital organs. In particular, the 
maintenance of coronary blood flow is directly associated with the possibility of achieving 
return of spontaneous circulation (ROSC), making it a crucial goal of CPR. However, even 
with high-quality chest compression, the rate of coronary blood flow usually remains <30% of 
that before cardiac arrest [4, 5]. 
Several studies have been conducted on methods that can improve coronary blood flow during 
CPR. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a procedure that 
is traditionally used for temporary hemorrhage control in patients with trauma by occluding 
the aorta via balloon dilation [6]. In cases of nontraumatic cardiac arrest, REBOA adjunct to 
CPR can increase coronary perfusion pressure (CPP) by occluding the aorta and rerouting 
blood circulation to the heart and brain rather than other organs, thereby ultimately help 

achieving ROSC [7]. By applying REBOA in cases of nontraumatic cardiac arrest, several 
animal studies have shown positive results for coronary blood flow in terms of hemodynamics 
[8]. Further, recent trials have revealed that the application of REBOA in humans has 
promising outcomes [9, 10]. However, despite such promising results in terms of hemodynamic 
changes, research on the effect of REBOA on clinical outcomes in patients with nontraumatic 
OHCA is lacking. 
 
Objectives {7} 
The current study aims to compare the clinical outcomes of CPR with REBOA and 
conventional CPR in patients with nontraumatic adult OHCA in the hospital stage. 
 
Trial design {8} 
The REBOA trial was designed as a parallel, randomized, controlled, multinational trial and 
registered at ClinicalTrials.gov (National Clinical Trial number: NCT06031623). Our study 
design is based on the SPIRIT 2013 checklist [11]. Figure 1 shows the enrollment schedule, 
interventions, and study duration. Figure 2 depicts the study algorithm. 

 
Fig. 1: Schedule of enrollment, interventions, and assessments according to the Standard Protocol Items: Recommendations 
for Interventional Trials (SPIRIT) guideline 

 
Fig 2. Study flow 
 
Methods: participants, interventions, and outcomes 
Study setting {9} 
This study will be conducted at two urban academic tertiary hospitals in Korea (Seoul 
National University Bundang Hospital, SNUBH) and Taiwan (Far Eastern Memorial Hospital, 
FEMH). SNUBH, a tertiary medical center in Seongnam in the southern Gyeonggi area, has a 

population of 3.1 million residents. As a 1,337-bed capacity hospital, SNUBH records 70,000 
emergency department (ED) visits annually. FEMH, the only tertiary medical center in New 
Taipei City, Taiwan, serves over 1.6 million residents in the western area of Greater Taipei. As 
a 1,415-capacity hospital, FEMH records approximately 10,000 ED visits monthly, which 
includes approximately 25 cases of nontraumatic OHCA. 
The emergency medical system (EMS) in South Korea is government-based and operates on 
a multi-tiered dispatch system is operated for suspected cardiac arrests. Two teams, each 
comprising two to three 3 members and located closest to the scene, are dispatched. The first 
team, upon arrival, initiates basic life support, which includes chest compressions (with a depth 
of 5cm at a compression rate of 100-120 per minute), bag-mask ventilations, and use of an 
automated external defibrillator (AED). Upon the second team’s arrival, Advanced Life 
Support (ALS) is initiated if feasible, involving gaining intravenous access, administering 
epinephrine, and securing an advanced airway (through either a supraglottic airway or 
endotracheal intubation). ALS, if provided, it is guided by an emergency physician via a video 
call. If it is determined during CPR at the scene that ROSC is unlikely to be rapidly achieved, 
preparations for transport immediately commence. Concurrently, upon the decision to initiate 
transport, notification is sent to the ED of the receiving hospital. This includes the patient's 
medical history and the details of the arrest circumstances identified thus far. All patients are 
transported to the hospital for further resuscitation. 
In the prehospital setting of Taiwan, when an emergency call is received, the dispatcher 
initially sends the first ambulance to the scene, equipped with a minimum of two emergency 
medical technicians (EMTs). If the dispatcher confirms the event as an OHCA during the call, 
additional ambulances, potentially a second or even a third, are dispatched to the site. 
Simultaneously, the hospital is notified to commence preparation. Following the protocol of 

the New Taipei City Fire Department, these EMTs are required to deliver advanced life support 
to all patients with OHCA before reaching the ED. This protocol includes mechanical chest 
compression (using LUCAS®  2, Stryker Medical, Kalamazoo, MI) at the center of the chest, 
maintaining a rate of 100 compressions per min and a depth of 5 cm. Advanced airway 
management, involving either endotracheal intubation or a supraglottic airway, defibrillation, 
and resuscitative medication administration (e.g., epinephrine or amiodarone) through 
intravenous or intraosseous routes if available, are part of the protocol. Following the initial 
CPR cycle, unless a prior “Do Not Resuscitate” order is in place, all patients are transported to 
the hospital for further resuscitation. 
 
Eligibility criteria {10} 
Written informed consent should be obtained from the legal representative prior to the 
research. All patients with witnessed nontraumatic adult OHCA who arrive at the ED from 9 
am to 5 pm on working weekdays in each country’s time zone will be assessed for eligibility. 
Inclusion criteria 
Patients aged 20–80 years with nontraumatic witnessed OHCA, arriving at the ED between 
9AM and 5PM in Korea, and 8AM to 8PM in Taiwan. 
Exclusion criteria 
The exclusion criteria include the following: 1) patients aged below 20 years old or over 80 
years old, 2) those with traumatic cardiac arrest; 3) those with unwitnessed cardiac arrest; 4) 
pregnant patients; 5) those who have already achieved ROSC upon arrival at the ED; 6) those 
with a precardiac arrest cerebral performance category (CPC) score of 3–4; 7) those showing 
evidence of cardiac arrest caused by bleeding (e.g., gastrointestinal bleeding); 8) those 

suspected of aortic disease, such as dissection, intramural hematoma, or aneurysm, using 
bedside ultrasound performed immediately after ED arrival or have a previous history of aortic 
disease; 9) those whose legal representatives request termination of resuscitation efforts before 
study enrollment; 10) those declared dead at scene before enrollment; and 11) those who meet 
the criteria for extracorporeal CPR (ECPR), and have been decided to receive ECPR. ECPR is 
applicable when all of the following criteria are met: precardiac arrest CPC score of 1–2; 
witnessed cardiac arrest with bystander CPR; aged 20–70 years; initial shockable rhythm; 
ECMO pump-on available within 60 min of cardiac arrest onset; and absence of end-stage 
diseases, such as cancer, liver cirrhosis, or end-stage renal failure. 
Patients will be evaluated for eligibility based on patient history for most items in the 
exclusion and inclusion criteria. Due to the EMS systems in Korea and Taiwan notifying the 
ED of incoming cardiac arrests 5–15 min prior to arrival, along with the patient’s history and 
circumstances of the cardiac arrest at the scene, clinicians will be able to reassess whether the 
patient meets the eligibility criteria to a certain extent. 
 
Need for informed consent {26a} 
As per the Declaration of Helsinki, obtaining informed consent is mandatory for any study 
involving human participants [12]. However, in the context of research on cardiac arrest 
research, securing informed consent from unconscious patients presents a considerable 
challenge [13]. Recognizing the necessity for prompt resuscitation, the United States Food and 
Drug Administration has outlined provisions to exempt the need for informed consent in certain 
emergency medical research scenarios [14]. 
At SNUBH, informed consent will be obtained upon ED arrival. Researchers will explain the 

purpose of the study, risks and benefits of the intervention, and possible complications. As 
patients with OHCA are unconscious during enrollment, written informed consent will be 
obtained from legal representatives; this consent form will include details about the study and 
provide information on how to reach the study investigator or ethics review board for any 
questions or concerns related to the research. If the patient regains consciousness and is 
adequately alert to comprehend the process, the researcher will explain the study protocol to 
the patient, and informed consent will be obtained. 
The current study was approved by the Institutional Review Board (IRB) of FEMH. In 
accordance with the abovementioned provisions, the IRB of FEMH waived the need for 
informed consent, irrespective of whether the trial participants were assigned to the 
intervention (REBOA-CPR) or control (conventional ACLS) group. However, if a participant 
achieves sustained ROSC, the researchers will then be required to obtain written informed 
consent from the participant’s legally authorized representative. 
 
Need for additional consent for the collection and use of participant data and biological 
specimens {26b} 
Biological specimens will not be collected. All data collected will be deidentified and then 
stored in an online database, which will only be available to the investigators with pre-
authorized ID and password. 
 

Interventions 
Explanation regarding the choice of comparators {6b} 
This trial aims to examine the clinical impact of REBOA in patients with nontraumatic adult 
OHCA. Accordingly, patients will be randomly assigned to the intervention or control group 
with the intention to treat. The intervention group will receive REBOA in addition to 
conventional ACLS. Conventional ACLS will be provided according to the 2020 American 
Heart Association (AHA) guidelines [3]. In both study institutions, invasive hemodynamic 
monitoring using arterial catheterization is a routine practice during ACLS. The control 
(conventional CPR) group will receive conventional ACLS according to the 2020 AHA 
guidelines with invasive hemodynamic monitoring. 
 
Intervention description {11a} 
In SNUBH, ACLS will be initiated and informed consent will be obtained from legal 
representatives simultaneously for eligible patients with OHCA upon ED arrival. At FEMH, 
eligible patients with OHCA will be enrolled in the study starting ACLS as soon as they arrive 
at the ED, as the IRB waived the acquisition of informed consent. After enrollment, patients 
will be randomly assigned to the intervention or control group. 
 
REBOA insertion 
While performing ACLS, the common femoral artery is accessed using an 8-french sheath 
catheter (Radifocus Introducer II, Terumo, Tokyo, Japan) based on the Seldinger technique 
under ultrasound guidance. Arterial catheterization is a routine intervention during ACLS at 

both institutions. Hence, an arterial catheter will be inserted, and arterial blood pressure (ABP) 
levels will be continuously monitored invasively during ACLS in both groups. 
In the REBOA-CPR group, the REBOA catheter (Rescue Balloon, Tokai Medical Products, 
Aichi, Japan) will be inserted through the sheath catheter. To position the REBOA catheter at 
zone 1, the length from the site of insertion to the site immediately distal to the xiphoid process 
will be measured, and the REBOA catheter will be placed at the measured length along the 
presumed pathway of the artery. If possible, an abdominal ultrasonography or portable chest 
radiography machine will be used to confirm whether the REBOA catheter is placed adequately. 
After placing the REBOA catheter, the balloon will be cautiously inflated until the balloon 
diameter reaches 25 millimeter or until the physician experiences resistance. ACLS will be 
continuously provided with the balloon in an inflated state. After REBOA catheter inflation, 
ABP levels will be monitored at the tip of the REBOA catheter. 
If the femoral artery is accessed via the sheath catheter and the patient is included in the 
intervention group, the REBOA catheter will be inserted immediately. 
 
Hemodynamic monitoring protocol 
ABP levels, central venous pressure (CVP) levels, electrocardiogram, and end-tidal carbon 
dioxide (ETCO2) levels will be continuously monitored and recorded during ACLS. ABP levels 
will be continuously monitored using the sheath catheter and REBOA catheter tip before and 
after balloon inflation, respectively. CVP levels will be measured via a central line placed 
during ACLS in the right internal jugular vein or subclavian vein under ultrasound guidance. 
ETCO2 levels will be monitored during ACLS to monitor the quality of chest compression and 
estimate cardiac output as an adjunct to ABP levels [15]. 

 
Postresuscitation care 
If the patient achieves ROSC, the REBOA balloon will be gradually deflated based on the 
discretion of the attending physician, if they judge that the risk of rearrest in a few minutes is 
low. Patients in both groups who achieved ROSC will receive postcardiac arrest care, including 
targeted temperature management (TTM), according to the 2020 AHA guideline [3]. If 
hypotension occurs, intravenous fluid and vasopressors will be administered as necessary. 
 
Criteria for discontinuing or modifying the allocated interventions {11b} 
Any participant or legal representatives who want to withdraw from the study will be allowed 
to do so without any consequences. If the legal representative of the patient chooses to 
withdraw from the study, the patient will continue to receive conventional CPR, similar to that 
provided to patients in the control group. 
 
Strategies to improve intervention adherence {11c} 
To improve adherence, regular meetings will be conducted to review and ensure protocol 
adherence. Regarding any protocol violations that are identified after intervention, additional 
meetings will be conducted to review each case. 
 
Relevant concomitant care permitted or prohibited during the trial {11d} 
There are no restrictions regarding concomitant care during the trial. Implementing the 
intervention will not require alteration to the usual management of cardiac arrest, which follows 

the 2020 AHA guidelines and applies to both trial arms. 
 
Provisions for post-trial care {30} 
The provisions for post-trial care in this study are within the scope of postcardiac arrest care 
according to the 2020 AHA guidelines. In addition to TTM, care will be based on the presumed 
etiology of cardiac arrest for each patient. In patients who achieved ROSC, any subsequent 
adverse events related to REBOA catheter insertion, such as vessel injury, lower limb ischemia, 
and hematoma/infection, which occurs at the insertion site of the REBOA catheter, will be 
monitored. In addition, possible related complications such as acute kidney which requires 
renal replacement therapy, acute respiratory distress syndrome, bacteremia, pneumonia, 
sepsis/septic shock, and paraplegia will be monitored. 
 
Outcomes {12} 
Primary outcome 
The primary outcome will be ROSC in the ED, which is represented by the number of patients 
who achieved ROSC regardless of sustained time. 
 
Secondary outcomes 
The secondary outcomes will be sustained ROSC (defined as ROSC maintained for at least 
20 minutes); survival to admission; survival to discharge; neurological outcome at discharge 
as well as 1, 3, and 6 months after ROSC; and hemodynamic changes at 1, 2, 4, and 10 minute 
after REBOA inflation. Data regarding complications associated with REBOA catheter 

insertion will also be considered as secondary outcomes. Information on neurological outcomes 
will be obtained using the CPC scale and modified Rankin scale (mRS). If the surviving 
patients are discharged, the research nurse will conduct phone interviews with them or their 
legal representatives to determine CPC and mRS scores at each time point. REBOA catheter 
insertion-related complications include direct or indirect adverse events such as malposition, 
insertion failure, hematoma/infection, femoral artery injury, lower limb ischemia, and aortic 
injury. 
 
Participant timeline {13} 
Figure 3 shows the participant timeline. 
 
Fig. 3. Participant timeline. ROSC, return of spontaneous circulation; PCAS, postcardiac arrest syndrome; TTM, targeted 
temperature management; CPC, cerebral performance category; mRS, modified Rankin scale 
 
Sample size {14} 
The primary outcome will be ROSC. Current data supporting the sample size of this study 
are limited. According to a pilot study on the application of REBOA in patients with 
nontraumatic OHCA, which was performed at one of the two institutions involved in the 
current study, 40% of patients achieved ROSC in the ED [10]. According to a study on 

conventional CPR for patients with OHCA, which was conducted at the same institution, 21.4% 
of patients achieved ROSC in the ED [13]. We used these differences to estimate the sample 
size with alpha values of 0.05 and a power of 0.8 and revealed that 212 patients (106 in each 
group) will be required. Finally, with a dropout rate of 10%, 234 patients should be enrolled, 
with equal proportions in each arm. 
Recruitment {15} 
Each hospital will assess all patients with nontraumatic adult OHCA for eligibility and 
continue to enroll patients until the specific sample size is reached. At least 50 patients will be 
enrolled competitively at each institution. 
 
Assignment of interventions: allocation 
Sequence generation {16a} 
The randomization sequence will be generated using R statistical software (version 4.1.3; R 
Core Team, R Foundation for Statistical Computing, Vienna, Austria). The randomized 
permuted block design with block sizes of 2, 4, and 6 will be employed. Randomization will 
be stratified by institution, ensuring that an equal number of participants are assigned to each 
treatment group in each institution. The sequence will be implemented using electronic case 
report form (CRF) software (MyECRF, LUNAAIR, Republic of Korea). 
 
Concealment mechanism {16b} 
Owing to the nature of the intervention, it will be challenging to blind the participating 
physicians during the study. Hence, no concealment mechanism will be employed. 

Randomization sequences will be concealed from the participating physicians. Group 
assignments will be blinded to the data analysts. Deidentified CRFs will be used to blind data 
analysts. Data from each group will be stored in electronic CRF as groups A and B. Thus, the 
data analyst will be blinded to the actual group. 
 
Implementation {16c} 
An independent statistician will generate an allocation sequence. The generated 
randomization sequence will be stored in electronic CRF (MyECRF, LUNAAIR, South Korea) 
and will not be released to the research team. If the emergency medical service team notifies 
the ED of the study institutions regarding incoming OHCA cases, the participating physician 
on call will assess eligibility and enroll participants. After enrollment, the researcher will 
disclose the allocation information stored in electronic CRF to the participating physician. 
 
Assignment of interventions: blinding 
Who will be blinded {17a} 
Owing to the nature of the study, neither the researcher nor the patient or legal representatives 
will be blinded. 
 
Procedure for unblinding if needed {17b} 
The design is an open label study, so unblinding will not occur. 
 

Data collection and management 
Plans for the assessment and collection of outcomes {18a} 
Demographic characteristics (such as age, sex, underlying medical condition, and CPC score 
before cardiac arrest), cardiac arrest details (time and place of arrest, witness of the arrest, 
bystander CPR and AED use, initial rhythm, EMS call time and arrival time, scene departure 
time, initial cardiac rhythm, established airway, chest compression via EMS, defibrillation 
energy and attempts, intravenous access, and medication administered), in-hospital information 
(time of ED arrival, time of central/arterial line insertion, established airway in the ED, 
medication administration, and ABP levels during ACLS), data regarding REBOA catheter 
insertion (insertion time and site, number of attempts, balloon inflation volume, and device-
related complications), patient outcomes (ROSC; sustained ROSC; time and location of ROSC; 
survival to admission; survival to discharge; in-hospital mortality; length of hospital/intensive 
care unit stay; good neurological outcome at hospital discharge as well as 1, 3, and 6 months 
after ROSC); and adverse events will be collected.  
The definition of cardiac arrest data will be recorded based on the Utstein Resuscitation 
Registry Templates for OHCA [16]. The primary outcome will be ROSC at any point during 
the resuscitation attempt in the ED. Sustained ROSC will be defined as maintaining the 
patient’s spontaneous circulation without chest compressions for >20 minutes. Further, good 
neurological outcomes are defined as CPC 1 and 2 [17]. Changes in hemodynamic parameters 
after REBOA insertion will be analyzed over time by obtaining a continuous blood pressure 
signal. 
 

Plans to promote participant retention and complete follow up {18b} 
Considering that our primary outcome is any ROSC in the ED, no loss to follow up until the 
primary outcome is checked after enrollment is expected. To assess secondary outcomes, the 
following plans will be implemented to promote participant retention and complete follow up. 
The researcher in charge of each institution will follow up with the patients who achieved 
ROSC and were discharged from the hospital to collect CPC scores at 1, 3, and 6 months. To 
reduce loss to follow up as much as possible, the study institution will make every reasonable 
effort to follow up with patients for the entire study period, including the discussion of their 
health status when assessing CPC via phone. 
Any decisions to withdraw from the study made by the trial participant or their legally 
authorized representative will be meticulously recorded, along with the reasons and precise 
timing of such actions. If a participant becomes inaccessible during the follow up period, the 
corresponding data will be marked as missing in the analysis. Ultimately, these exhaustive 
details regarding withdrawal will be incorporated into the Consolidated Standards of Reporting 
Trials flow diagram, thus providing a transparent and integrated overview of participant 
retention throughout the study. 
 
Data management {19} 
Data will be entered into electronic CRF, which will be accessible only to the researcher in 
charge. Each data item will have a designated range (e.g., 18–150 years for age). If the value 
for a particular item falls outside this range, an immediate warning will be issued. Furthermore, 
if the value lies within the appropriate range but does not meet specific conditions (e.g., the 
recorded time of arterial line insertion precedes the arrival time at the ED), a query will be 

forwarded to the researcher in charge for necessary corrections. 
 
Confidentiality {27} 
Data will be stored based on the study number assigned to each participant. Paper CRFs will 
be stored in locked file cabinets in the laboratory. Data will also be transferred to electronic 
CRFs by the researcher in charge, and only researchers who have been authorized in advance 
will have access to this system. 
 
Plans for collection, laboratory evaluation, and storage of biological specimens for 
genetic or molecular analysis in this trial/future use {33} 
This study will not require biological specimens for genetic or molecular analysis. 
 
Statistical methods 
Statistical analysis of the primary and secondary outcomes {20a} 
Data analysis will be performed using R statistical software (version 4.1.3; R Core Team, R 
Foundation for Statistical Computing, Vienna, Austria). The Shapiro–Wilk test will be used to 
assess data normality. Continuous data that follow a normal distribution will be presented as 
the mean ± standard deviation and further analyzed using independent t-test. In contrast, data 
not adhering to a normal distribution will be expressed as median and interquartile range and 
further evaluated using the Mann–Whitney U test. Categorical variables, including ROSC and 
survival, will be presented as frequencies (percentages) and analyzed using the chi-square test 
or Fisher’s exact test, as appropriate. For variables demonstrating statistically significant 

differences between the two groups, the disparity will be reported as either absolute difference 
or risk difference, depending on the variable type. The analysis of the primary outcome 
difference between the two groups will use both absolute difference and risk difference. 
Additionally, when applicable, the risk ratio will be presented as an additional measure, as 
appropriate. P-values of <0.05 will be considered to indicate statistical significance. In interim 
analysis, the significance level according to the O’Brien–Fleming approach will be used. A 
Statistical Analysis Plan will be attached separately. 
 
Interim analysis {21b} 
After the enrolment of the first 116 patients, an interim analysis will be performed according 
to the O’Brien–Fleming rule. A blinded interim analysis will be performed by an independent 
statistician. Both primary and secondary outcomes will be assessed using interim analysis. If 
there is a statistically significant difference in ROSC, sustained ROSC, or survival to discharge 
between the two groups, with a significance level of 0.005, the trial will be considered for 
termination. 
The sample size will be recalculated based on the assumption that the current difference in 
the primary endpoint between the two groups will persist. (1) If the sample size required to 
prove a difference exceeds three times the initially planned sample size (with a power of 0.80 
and significance level of 0.05), the Trial Steering Committee (TSC) will decide whether to 
continue the trial. (2) If the recalculated sample size falls within the range of 348–696 (150%–
300% of the original sample size), the TSC will discuss whether the study should proceed with 
the new sample size. (3) If the revised sample size is <348 (150% of the original sample size), 
the study will proceed with the adjusted sample size. 

 
Methods for additional analysis {20b} 
Additional subgroup analysis will aim to investigate factors potentially leading to disparities 
in treatment outcomes, thereby indicating that these effects may vary based on the distinct 
clinical characteristics of patients throughout the study. This detailed evaluation will be 
conducted in various potential subgroups of age, sex, administration of CPR using a bystander, 
initial rhythm (categorized as shockable or nonshockable), location of the arrest (public vs. 
nonpublic), presumed cause of arrest, time elapsed from arrest to arrival at the ED, and the 
institution where the patient received treatment (SNUBH or FEMH).  
 
Analysis method for handling protocol nonadherence and statistical methods for 
handling missing data {20c} 
For statistical analysis, two sets will be utilized: intention-to-treat set and per-protocol set. 
The intention-to-treat set will analyze patients based on the group they were assigned to after 
randomization, regardless of the actual randomized treatment received. The per-protocol set 
will identify patients who received or did not receive REBOA (REBOA or conventional group, 
respectively) for analysis. In the per-protocol analysis, patients allocated in the REBOA group 
who achieved ROSC before REBOA insertion are analyzed as part of the conventional group. 
However, as early ROSC may indicate a more favorable prognosis, this adjustment has the 
potential to introduce bias. To mitigate this bias and provide a more accurate assessment of 
treatment effects, such patients will be excluded from the REBOA group. Similarly, patients 
in the conventional group who achieved ROSC within the corresponding timeframe as those in 
the REBOA group will also be excluded. 

Authors expect no missing data for the primary outcome (any ROSC), which is immediately 
determined in all patients after the termination of ACLS. When reporting patient clinical 
characteristics and secondary outcomes, the primary approach to handling missing data will be 
the direct deletion method. However, in cases where a significant amount of missing data exists 
for specific clinical characteristics, multiple imputation will be considered as an alternative 
approach. If multiple imputation is employed for any variable, it will be explicitly stated in the 
results. 
 
Plans to provide access to the full protocol, participant level data, and statistical code 
{31c} 
The patient-level dataset will not be accessed by the public. 
 
Oversight and monitoring 
Composition of the coordinating center and TSC {5d} 
Four committees will play roles in the research: Trial Steering Committee, Trial Management 
Group, Data Monitoring Committee, and the Data Coordinating Center. 
Trial Steering Committee (TSC): The TSC, comprising six members, includes an 
independent chair, an independent statistician, an independent member, and three non-
independent members from each participating institution. The TSC oversees patient safety, 
ensures data integrity, and makes executive decisions, such as modifications to or 
discontinuation of the study protocol. 
Trial Management Group (TMG): The TMG, consisting of two clinicians from each 

participating institution, is responsible for overseeing the day-to-day execution of trial 
performance. Communication within the TMG occurs online as necessary. 
Data Monitoring Committee (DMC): The DMC, comprising four members, including one 
statistician, all independent from the trial, reviews efficacy and safety data, conducts interim 
analyses, oversees recruitment, assesses data quality, monitors protocol deviations, and 
addresses safety and adverse events. The DMC meets every 6 months and provides 
recommendations to the TSC. 
Data Coordinating Center (DCC): The DCC, with two members—one from each 
participating institution—regularly assesses trial data quality using electronic CRF (eCRF) 
software. 
 
Composition, role, and reporting structure of the DMC {21a} 
The trial will be independently monitored by the DMC, which will review the safety and 
efficacy of the trial and send biannual reports to the TSC. 
 
Reporting of adverse events {22} 
Adverse events will be monitored from randomization to hospital discharge. If any adverse 
events occur, patients will be treated immediately according to routine practice and followed 
up until resolution or treatment termination. Such adverse events will be reported by the DMC 
to the TSC and IRB. 
All adverse events will be recorded in CRFs for each case. Table 2 presents a list of adverse 
events that will be recorded. All adverse events and complications associated with REBOA 

catheter insertion will be analyzed and reported as secondary outcomes. 
 
Frequency and plans for auditing trial conduct {23} 
The DMC will convene every six months to analyze and review trial safety. Basic patient 
demographic characteristics, adequacy of patient recruitment, protocol deviations, adequacy of 
follow up, and serious adverse events will be reported. Although the meeting will be conducted 
independently from the study investigators, any information or issues that are deemed 
necessary will be reported to the TSC and IRB. 
Electronic CRF software employs formulas and conditions to assess data quality. If any input 
value does not satisfy a condition, an automatic query will be raised, and the DCC will evaluate 
the patient’s original CRF (paper copy) and correct the input value if necessary. If an error 
occurs despite similar values in paper and electronic CRFs, then the TMG will be informed, 
and the error will be corrected and reported to the TSC. The DCC will also assess data 
completeness on a daily basis and may ask the TSC to add/modify/delete formulas and 
conditions if necessary. 
 
Plans for communicating important protocol amendments to relevant parties {25} 
Any modifications to the protocol that may affect the study conduct, potential patient benefits, 
or patient safety, including changes to the study objectives, study design, patient population, 
sample size, study procedures, or important administrative aspects, will require notification to 
the sponsor first. Subsequently, a copy of the revised protocol will be sent to the TSC The 
revised protocol will undergo review by the TSC, and the final decisions made by the TSC will 
receive approval from IRB of each participating institution. Following approval, the revised 

protocol will be incorporated into the investigator site file, and the trial registration will be 
updated accordingly. Any deviations from the protocol will be thoroughly documented using a 
breach report form. 
 
Dissemination plans {31a} 
Our findings will be disseminated via journal publications and conference presentations. 
 
Discussion 
To achieve ROSC in cardiac arrest, coronary perfusion should be restored [5, 18]. CPP, which 
is calculated as the difference between aortic and diastolic right atrial pressure levels during 
the relaxation phase of chest compressions, indicates myocardial perfusion and CPR quality [5, 
18]. 
REBOA, a mechanical technique capable of increasing CPP, serves as an alternative to the 
currently used method [19]. Demonstrating promising outcomes in animal models and pilot 
studies, REBOA may offer a feasible alternative or supplementary treatment approach to 
achieve favorable clinical results in patients with nontraumatic OHCA [20]. A study to observe 
the utility of REBOA in nontraumatic cardiac arrest is currently underway in Norway [21]. The 
primary outcome of this study is the proportion of ROSC, with a goal of enrolling 200 patients 
with a 1:1 allocation. However, this study is focused on the application of REBOA in the 
prehospital setting. The upcoming parallel-group, randomized controlled trial will be 
conducted at two academic tertiary hospitals in South Korea and Taiwan, focusing on hospital 
settings. Further, it will evaluate whether REBOA can significantly improve the current OHCA 
treatment practices, focusing primarily on achieving ROSC and secondarily on evaluating 

sustained ROSC and neurological outcomes in the patient population. 
In addition, there has been a recent report regarding the use of REBOA in trauma patients 
with exsanguinating hemorrhage [22]. The study suggests that in cases of trauma-related 
exsanguinating hemorrhage, REBOA did not reduce mortality. Since the primary focus of  this 
study is on patients with traumatic hemorrhage, a disease entity distinct from non-traumatic 
cardiac arrest, interpreting results from this study to non-traumatic cardiac arrest patients may 
be challenging. Despite the differences in subjects, it is crucial not to overlook the possibility 
that similar results may emerge in our current study. 
By investigating REBOA as a means to enhance CPP during CPR, our study aims to explore 
alternative treatment protocols that may contribute to more effective outcomes in patients with 
nontraumatic OHCA. The research results may provide valuable insights and add to the 
growing body of evidence that may help improve treatment strategies for nontraumatic OHCA. 
Ultimately, these study findings can be an important step toward further advancements and 
innovations in this important area of public health. 
 
Trial status 
Recruitment will start in October 2023 and end in September 2025. The current version of 
the protocol is version 1.3 (January 24, 2025). 
 
Abbreviations 
Advanced Cardiovascular Life Support (ACLS) 
Advanced Life Support (ALS) 

American Heart Association (AHA) 
Arterial Blood Pressure (ABP) 
Automated External Defibrillator (AED) 
Cardiopulmonary Resuscitation (CPR) 
Case Report Form (CRF) 
Central Venous Pressure (CVP) 
Cerebral Performance Category (CPC) 
Coronary Perfusion Pressure (CPP) 
Data Coordinating Center (DCC) 
Data Monitoring Committee (DMC) 
Emergency Department (ED) 
Emergency Medical System (EMS) 
End-tidal Carbon Dioxide (ETCO2) 
Extracorporeal Cardiopulmonary Resuscitation (ECPR) 
Far Eastern Memorial Hospital (FEMH) 
Institutional Review Board (IRB) 
Modified Rankin Scale (mRS) 
Out-of-hospital Cardiac Arrest (OHCA) 
Resuscitative Endovascular Balloon Occlusion Of The Aorta (REBOA) 

Return of Spontaneous Circulation (ROSC) 
Seoul National University Bundang Hospital (SNUBH) 
Targeted Temperature Management (TTM) 
Trial Management Group (TMG) 
Trial Steering Committee (TSC) 
 
Declarations 
Acknowledgments 
The authors thank Division of Statistics in Medical Research Collaborating Center at Seoul 
National University Bundang Hospital for statistical analyses. 
 
Funding {4} 
This work is partly supported by a National Research Foundation of Korea (NRF) grant 
funded by the Korean government (no. NRF-2022R1F1A1074361), the Seoul National 
University Bundang Hospital Research Fund (no. 14-2019-021), and Far Eastern Memorial 
Hospital (no. PI20230002). 
 

Availability of data and materials {29} 
The study results will be published through conferences and scientific publications in medical 
journals related to emergency medicine or resuscitation. Deidentified data will be available for 
online provision upon reasonable request. 
 
Patient Public Involvement 
There was no patient public involvement in the process of developing this trial protocol. 
Plans for seeking research ethics committee/IRB approval {24} 
This study protocol and the informed consent forms has been reviewed by the IRB of both 
institutions (SNUBH IRB no.: B-2302-811-001, FEMH IRB no.: 112075-F). 
 
Consent for publication {32} 
Each institution has its own consent form, and all forms have been approved by their 
respective IRBs. The consent form included the title and purpose of the study, a description of 
the possible benefits and harms to the patients, the name of the principal investigator, contact 
information for questions about the study, and details regarding the possible adverse events 
and their management. 
 
Competing interests {28} 
There are no competing interests to declare. 

 
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Title: Effects of Resuscitative Endovascular Balloon Occlusion of the 
Aorta on Nontraumatic Out-of-hospital Cardiac Arrest (REBOA): A 
Multinational, Multicenter Randomized Controlled Trial 
 
 
Trial Registration Number: NCT06031623 
 
Current Version Number: Version 1.01 
Release Date: January 24, 2025 
 
Version History: 
V1.01 
 
 

Contributors and Affiliations 
Seoul National University Bundang Hospital Dong Keon Lee 
Seoul National University Bundang Hospital You Hwan Jo 
Seoul National University Bundang Hospital Seung Min Park 
Seoul National University Bundang Hospital Dong-Hyun Jang 
Seoul National University Bundang Hospital Hee Eun Kim 
Medical Research Collaborating Center, SMG-SNU Boramae Medical Center So Hee Oh 
Far Eastern Memorial Hospital Jen-Tang Sun 
Far Eastern Memorial Hospital Sheng-En Chu 
Far Eastern Memorial Hospital Xuan-An Chen 
National Taiwan University Hospital Wen-Chu Chiang 
National Taiwan University Hospital Statistical Consulting Unit Chin-Hao Chang 
 
Signatures 
 
 
 

1. 
Introduction 
1.1. 
Background and Rationale 
Out-of-hospital cardiac arrest (OHCA) is a medical emergency that remains a public health 
issue worldwide. The primary management approach for cardiac arrest emphasizes immediate 
attention and treatment, including early recognition, high-quality chest compressions, early 
defibrillation for shockable rhythms, early epinephrine administration, and advanced airway access 
as soon as possible. Apart from the development of these guidelines, substantial international efforts 
have been directed toward increasing survival rates and improving the prognosis of patients with 
OHCA. However, despite these undertakings, fewer than 10% of OHCA patients in many countries 
survive, and even fewer show good neurological prognosis at discharge. 
Cardiopulmonary resuscitation (CPR) primarily aims to reduce ischemic damage during 
cardiac arrest by maintaining blood flow to vessels supplying vital organs. Maintaining coronary 
blood flow, which supplies blood to the heart, is directly associated with the likelihood of achieving 
return of spontaneous circulation (ROSC). However, even with high-quality chest compressions, 
coronary blood flow typically remains at less than 30% of the pre-cardiac arrest levels. 
Several studies have sought to determine how to improve the coronary blood flow during 
CPR. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is traditionally used in 
trauma patients for temporary hemorrhage control by occluding the aorta via balloon dilation. By 
occluding the aorta and redirecting blood circulation toward the heart and brain rather than other 
organs during cardiac arrests, REBOA can assist in increasing the coronary perfusion pressure, 
which consequently helps achieve ROSC. Several animal studies have shown that applying REBOA 
to nontraumatic cardiac arrest patients promotes positive hemodynamic results in terms of coronary 
blood flow, and recent trials on its application in humans have also shown promising results (Brede 
et al. 2019; Jang et al. 2022). However, despite these encouraging findings related to hemodynamic 
changes, research on the effects of REBOA on clinical outcomes in patients with nontraumatic 
OHCA remains limited. 
 
1.2. 
Study Objectives and Hypothesis 
This trial primarily aims to evaluate the clinical impact of REBOA in nontraumatic OHCA 
patients and compare with that of conventional advanced cardiac life support (ACLS). The 

hypothesis of this study is that OHCA patients treated with REBOA are more likely to achieve 
ROSC than those receiving traditional ACLS alone. 
 
2. 
Study Methods 
2.1. 
Trial Design 
This prospective, multicenter, open-label, parallel-group, randomized controlled trial will 
be conducted in two tertiary hospitals: Seoul National University Bundang Hospital in South Korea 
and Far Eastern Memorial Hospital in Taiwan. Patients who are transported intra-arrest and satisfy 
all inclusion criteria without any exclusionary factors will be promptly and randomly assigned on a 
1:1 basis to either the REBOA CPR group or the conventional CPR group immediately upon arrival 
at the emergency department (ED). The primary aim of this study was to compare post-CPR 
prognosis between the two patient cohorts. 
 
2.2. 
Randomization 
The randomization sequence will be generated using the R statistical software (version 4.2.3; 
R Core Team, R Foundation for Statistical Computing, Vienna, Austria). A randomized permuted 
block design with block sizes of 2, 4, and 6 will be used. Randomization will be stratified according 
to the institution, ensuring an equal number of participants assigned to each treatment group at each 
institution. The sequence will be implemented in electronic case report form software (MyECRF, 
LUNAAIR, Republic of Korea). 
 
2.3. 
Sample Size 
2.3.1. 
Sample Size Calculation 
A pilot study on the application of REBOA in nontraumatic OHCA patients at one 
institution in the present study found that the rate of achieving ROSC in the ED was 40.0%. Another 
study involving the application of the conventional CPR method for OHCA patients at the same 
institution showed that the rate of achieving ROSC in the ED was 21.4%. 

Using this difference, the sample size was calculated using an alpha of 0.05 and a beta of 
0.8, which revealed that a total of 210 patients were required. Assuming a dropout rate of 10%, this 
study will seek to enroll 232 patients (116 per arm; a minimum of 52 per site for competitive 
recruitment). 
2.3.2. 
Number of Subjects per Center 
Patients will be enrolled competitively with a minimum requirement of 50 at each 
institution. This has been established to maintain statistical balance and analytical rigor, fostering a 
reliable and comparative examination of data from these distinct sites. This approach forms a key 
part of our statistical analysis plan and will aid in achieving meaningful and reliable results. 
 
2.4. 
Framework 
The analytical framework of this study is designed to evaluate the comparability of outcomes 
between the two CPR strategies: CPR with REBOA and conventional CPR. Consequently, to 
thoroughly assess the comparability of outcomes, we undertake a two-tailed approach for our 
hypothesis testing. 
 
2.5. 
Statistical Interim Analyses and Stopping Guidance 
After enrolling the first 116 patients, an interim analysis will be performed according to the 
O'Brien–Fleming rule. An independent statistician will perform a blinded interim analysis. The 
primary (ROSC) and secondary outcomes will be assessed in the interim analysis using a 
significance level of 0.005 following the O’Brien–Fleming approach. 
The sample size will be recalculated based on the assumption that the current difference in the 
primary endpoint between the two groups will persist. (1) If the recalculated sample size needed to 
demonstrate a difference exceeds three times our initially planned sample size (assuming a power of 
0.80 and significance level of 0.05), then the Trial Steering Committee (TSC) will decide whether 
to continue with the trial. (2) If this recalculated sample size ranges between 348 and 696, which is 
150% to 300% of our initial estimate, then the TSC will discuss whether to adjust our study to reflect 
this new sample size. (3) If this revised calculation falls below 348, which is less than or equal to 
150% of our original estimate, then we proceed with this adjusted number for our sample size. 

 
2.6. 
Timing of Final Analysis 
The final analysis for this research study will occur 6 months after the enrollment of the last 
participant. This timeline was strategically devised to align with the sequential follow-ups planned 
at the end of the 1st, 3rd, and 6th months after enrollment. Meticulous planning will allow for a 
comprehensive understanding of the data gathered at these critical time intervals, thereby enhancing 
the overall credibility and reliability of the study findings. 
 
2.7. 
Timing of Outcome Assessments 
The outcomes of ROSC, including both ROSC and sustained ROSC, and changes in mean 
arterial blood pressure will be evaluated during resuscitation efforts subsequent to the admission of 
participating patients to the ED. After achieving ROSC, survival to admission will be assessed based 
on the patient’s transition from ED to inpatient hospitalization. Survival to discharge and 
neurological prognosis will be evaluated at the time of discharge. Post-discharge follow-up 
evaluations for survival and neurological functionality will be conducted via telephone interviews 
at any given time in the week for the 1st, 3rd, and 6th months after ROSC. This comprehensive 
evaluation strategy aimed to accurately capture and analyze the complete progression and potential 
recovery trajectories of our study participants. To minimize loss to follow-up as much as possible, 
staff at each study site will make every reasonable effort to maintain contact with patients throughout 
the entire study period. This includes discussing their health status when assessing the Cerebral 
Performance Category (CPC) during phone calls. 
 
3. 
Statistical Principles 
3.1. 
Confidence Intervals and P-values 
All statistical hypotheses in this study will be subjected to rigorous testing at a significance 
level of 0.05. This standard threshold for significance ensures the robustness of our findings and 
minimizes the likelihood of false–positive results. Furthermore, we reported our results with 95% 
confidence intervals for additional validity and precision. This commonly adopted approach 

underscores our confidence that the true population parameter lies within this defined range, thereby 
providing a reliable and comprehensive representation of our study findings. 
 
3.2. 
Adherence and Protocol Deviations 
This study defined adherence to the intervention as the proportion of patients initially assigned 
to the REBOA CPR group who will have undergone aortic occlusion. This approach reflects real-
world circumstances and captures the extent of exposure to the intervention, considering the time-
sensitive nature of applying the REBOA upon hospital arrival. Adherence to the intervention will be 
quantitatively expressed in terms of percentages to depict the proportion of patients who actually 
received aortic occlusion in the REBOA CPR group. 
Protocol deviations will be identified as instances in which patients in the REBOA group did 
not receive the aortic occlusion as planned. These deviations will be systematically assessed and 
summarized, focusing on the reasons why aortic occlusion was not achieved in the intervention 
group. A summary of protocol deviations will provide a detailed breakdown of the reasons for the 
deviation and their respective proportions within the intervention group. 
 
3.3. 
Analysis Populations 
Two distinct analytical population sets will be used. The first is the intention-to-treat set, which 
examines patients based on their initial randomized group assignment, irrespective of the ultimately 
administered treatment. The second is the per-protocol set, which specifically analyzes patients who 
did (the REBOA group) and did not (the non-REBOA group) undergo the REBOA procedure. In 
the per-protocol analysis, patients allocated in the REBOA group who achieved ROSC before 
REBOA insertion are analysed as part of the conventional group. However, as early ROSC may 
indicate a more favorable prognosis, this adjustment has the potential to introduce bias. To mitigate 
this bias and provide a more accurate assessment of treatment effects, such patients will be excluded 
from the REBOA group. Similarly, patients in the conventional group who achieved ROSC within 
the corresponding timeframe as those in the REBOA group will also be excluded. 
The safety analysis for this study will encompass all patients who will have undergone an 
attempt at REBOA placement, which is characterized by any attempt to puncture the femoral vessels. 
This indicates regardless of whether the insertion of the REBOA catheter into the target vessel or 

accomplishment of aortic occlusion was successful. The purpose of this population was to critically 
evaluate the safety of implementing REBOA in a CPR scenario. This evaluation guarantees 
comprehensive accounting of the potential safety considerations associated with the intervention. 
 
4. 
Trial Population 
4.1. 
Eligibility 
4.1.1. 
Inclusion Criteria 
All witnessed OHCA patients will be assessed for eligibility. The inclusion criteria for 
the study will be nontraumatic, witnessed OHCA patients between the ages of 20 and 80. 
4.1.2. 
Exclusion Criteria 
Exclusion criteria for the study are as follows: (1) age below 20 years or over 80 years; 
(2) traumatic cardiac arrests; (3) unwitnessed cardiac arrests; (4) pregnant patients; (5) 
patients who already achieved ROSC upon arrival at the ED; (6) pre-cardiac arrest CPC of 
3–4; (7) evidence of cardiac arrest due to bleeding (e.g., gastrointestinal bleeding); (8) those 
suspected of having aortic diseases, such as dissection, intramural hematoma, or aneurysm 
based on bedside ultrasound performed immediately after ED arrival or those who have a 
history of aortic disease and whose legal representative had requested termination of 
resuscitation efforts before study enrollment; and (9) patients who satisfy the criteria for 
extracorporeal cardiopulmonary resuscitation (ECPR) and who received ECPR. The ECPR 
criteria are applied when all of the following criteria are satisfied: pre-cardiac arrest CPC of 
1–2, witnessed cardiac arrest with bystander CPR, initial shockable rhythm, ECMO pump-
on available within 60 min of cardiac arrest onset; and patients without end-stage diseases, 
such as cancer, liver cirrhosis, or end-stage renal failure. 
 
4.2. 
Recruitment 
Each hospital will assess all OHCA patients for eligibility and will continue until the target 
number of patients is reached. Enrollment will be continuously monitored to ensure that each 
hospital can enroll 50% of its total population. A minimum of 50 patients will be enrolled 

competitively to minimize racial differences. The Consolidated Standards of Reporting Trials 
(CONSORT) flowchart is as follows: 
 
 
Figure 1. Consolidated Standards of Reporting Trials (CONSORT) flowchart 
 
4.3. 
Withdrawal or Loss Follow-up 
The withdrawal level at every stage of the study, whether during the intervention or follow-up 
phase, will be quantified as a percentage. Any decision to withdraw from the study, made by either 
the trial participant or their legally authorized representative, will be meticulously recorded, 

encapsulating the reasons and precise timing of such actions. If a participant becomes inaccessible 
during the follow-up period, their data will be considered missing during the analysis. Ultimately, 
these exhaustive details regarding withdrawal will be incorporated into the CONSORT flow diagram 
to provide a transparent and integrated overview of participant retention throughout the course of 
the study. 
 
4.4. 
Baseline Patient Characteristics 
Demographics (age, gender, and underlying disease), arrest data (timing and place of arrest, 
bystander CPR, initial rhythm, etc.), in-hospital data (arrival time, time of central/arterial line 
placement, etc.), outcome, and adverse events will be collected and are presented (Table 1). 
 
Data related to REBOA placement, including the time of placement, volume of balloon 
inflation, and depth of placement, will also be meticulously recorded and encapsulated within a table 
(Table 2) for a comprehensive review and reference. 

 
5. 
Analysis 
5.1. 
Outcome Definitions 
5.1.1. 
Primary Efficacy Endpoints 
● Any ROSC, defined as an occurrence in which a post-CPR patient 
establishes a palpable pulse that endures for a duration exceeding 1 min. 
5.1.2. 
Secondary Efficacy Endpoints 
● Change in mean arterial blood pressure 1 min after balloon inflation. 
● Sustained ROSC is defined as an occurrence in which a post-CPR 
patient establishes a palpable pulse that endures for a duration exceeding 
20 min. 

● Survival to hospital admission. 
● Survival to hospital discharge. 
● CPC score at the 1st, 3rd, and 6th month after ROSC. 
CPC scores were defined as follows: 
● CPC 1: Good cerebral performance—The patient is conscious, alert, and able 
to work. There might be slight neurological or psychological deficit. 
● CPC 2: Moderate cerebral disability—The patient is conscious and has 
sufficient cerebral function for independent activities of daily life. The patient 
could work in a sheltered environment. 
● CPC 3: Severe cerebral disability—The patient is conscious but dependent on 
others for daily support because of impaired brain function. 
● CPC 4: Coma or vegetative state—The patient is unconscious, with no 
meaningful interaction with the environment. 
● CPC 5: Brain death—The patient had no measurable brain function. 
 
5.2. 
Analysis Methods 
The Shapiro–Wilk test will be used to assess the normality of the data. Continuous data that 
follow a normal distribution will be presented as means and standard deviations and further analyzed 
using an independent t-test. In contrast, data not adhering to a normal distribution will be expressed 
as medians coupled with their interquartile ranges (IQRs) and evaluated using the Mann–Whitney 
U test. Numerical variables, such as the CPC score, will also be presented as medians with IQRs and 
analyzed using the Mann–Whitney U test. Categorical variables, including ROSC and survival, will 
be presented as frequencies (percentages) and analyzed using the chi-squared test or Fisher's exact 
test, as appropriate. Statistical significance was set at p value < 0.05. All the outcome analyses are 
presented in Table 3. 
 

 
 
5.3. 
Missing Data 
We expect no missing data for the primary outcome of this study, given that it can be 
determined immediately when CPR is terminated, either due to ROSC or a determination of death 
in the EDs. Regarding the reporting of the clinical characteristics of patients and secondary outcomes, 
the primary approach to handling missing data is the direct deletion method. However, in cases 
where a significant amount of missing data exists for specific variables among the clinical 
characteristics, multiple imputation is considered an alternative approach. If multiple imputation is 
employed for any variable, it is explicitly stated in the reporting of results. 
 
5.4. 
Additional Analyses 
The objective of the additional subgroup analysis is to investigate the factors potentially causing 
disparities in treatment outcomes, which may vary based on the distinct clinical characteristics of 
patients throughout the study. This detailed evaluation will be conducted for various potential 
determinants, including age, gender, whether CPR was administered by a bystander, initial rhythm 
(categorized as shockable or non-shockable), location of the arrest (public vs. non-public), cause of 
arrest (cardiogenic vs. non-cardiogenic), time elapsed from arrest to arrival at the ED, and the 
institution where the treatment was received (Seoul National University Bundang Hospital or Far 
Eastern Memorial Hospital). 
 

5.5. 
Harms 
Adverse events will be monitored from randomization to hospital discharge. Any adverse 
events, including malposition, insertion failure, insertion site hematoma/infection, femoral artery 
injury, lower limb ischemia, aorta injury, and others, will be recorded in the case report form for 
each case. If any adverse events occur, patients will be treated immediately according to routine 
practice and will be followed up until complete resolution or termination of treatment. Such adverse 
events will be reported to the TSC and IRB. 
 
5.6. 
Statistical Software 
 
Data will be analyzed using the R statistical software (version 4.2.3; R Core Team, R 
Foundation for Statistical Computing, Vienna, Austria). 

 
 
 
 
 
 
 
Seoul National University Bundang Hospital 
Informed Consent 
 
Effect Of Resuscitative Endovascular Balloon Occlusion of the Aorta in Non-Traumatic Out-
of-Hospital Cardiac Arrest (REBOA); A Multinational, Multicenter Randomized Controlled 
Trial 
 
 
 
 

Subject Information Sheet 
Subject Screening Number: ________________ 
 
Title of the Study: Effect Of Resuscitative Endovascular Balloon Occlusion of the Aorta in Non-
Traumatic Out-of-Hospital Cardiac Arrest (REBOA); A Multinational, Multicenter Randomized 
Controlled Trial 
 
Principal Investigator: Professor Dong Keon Lee, Department of Emergency Medicine, Bundang 
Seoul National University Hospital 
We kindly request your participation in this study.  
Before deciding to participate, it is important for you to fully understand why this study is being 
conducted and what your involvement will entail.  
The following information is provided to explain the details of this study, your role in it, and the 
process of the research. Please take sufficient time to read this subject information sheet, and if 
desired, discuss it with your family or others. Additionally, if you have any questions, please ask 
the exam coordinator or other study personnel, and carefully consider your decision to participate 
in this study. 
1. This study is conducted for research purposes.  
This clinical trial is not conducted for therapeutic purposes. It is a research study aimed at 
investigating the impact of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) 
during cardiopulmonary resuscitation on the prognosis of out-of-hospital cardiac arrest patients, 
with the goal of improving the prognosis of cardiac arrest patients. 
2. Background and Purpose of the Clinical Trial 
For out-of-hospital cardiac arrest (OHCA), cardiopulmonary resuscitation (CPR) is performed. 
However, even with high-quality CPR, the rate of return of spontaneous circulation (ROSC) is 
extremely low. The primary goal of CPR is to maintain sufficient blood flow to the brain and 
coronary arteries, preventing ischemic damage and correcting the reversible causes of cardiac 
arrest. However, even with effective chest compressions, only 30% of the pre-arrest blood flow to 
vital organs is achieved. This study aims to increase the rate of ROSC by using REBOA during CPR, 
which involves occluding the descending aorta to increase blood flow to major organs during 
resuscitation. 
3. Information on Investigational Drugs/Medical Devices and Randomization Probability 
This study will be conducted using randomization. The assignment to either the CPR group or the 
REBOA group will be determined randomly based on a computer-generated randomization table, 

with an equal allocation ratio of 1:1. This study is a multinational study, with a total of 232 patients 
participating from Taiwan and Korea. If you agree to participate in the study, you will be randomly 
assigned to either the control or experimental group. 
 
4. Various Tests and Procedures that Subjects will Undergo in the Clinical Trial 
Both groups will receive CPR according to the 2020 American Heart Association guidelines for 
cardiopulmonary resuscitation. This standard CPR includes high-quality chest compressions at a 
rate of 100-120 per minute, prevention of hyperventilation, early defibrillation, and administration 
of medications such as epinephrine. 
After the randomization process, if assigned to the control group, you will receive standard CPR 
as described above.  
If assigned to the experimental group, in addition to the standard CPR 
according to the guidelines, femoral arterial access will be obtained, and 
a REBOA catheter will be inserted through the access. The catheter will be 
positioned within the aorta. The catheter will be inserted to an adequate 
length, and the balloon attached to the catheter will be positioned in the 
chest. Saline solution will be injected into the balloon to inflate it, 
obstructing the aorta, and preventing unnecessary blood flow to the 
lower body (Figure 1). Additionally, the catheter, arterial access, and other 
vital sign monitoring devices will be used to monitor hemodynamic 
parameters, including blood pressure, during CPR. If a return of 
spontaneous circulation is achieved, the REBOA will be removed after 
stabilization. 
 
Figure 1. Schematic diagram of REBOA 
 
The expected participation period for research subjects is one year, and they will be contacted by 
phone to measure neurological outcomes after treatment completion. 
 
5. Compliance requirements for research subjects 
There are no specific compliance requirements for research subjects. They may be contacted by 
phone to investigate neurological outcomes one year after resuscitation. Contact information for 
patients and caregivers will be collected for phone calls. 
 
 

6. The fact that it is an unproven clinical trial 
In cardiac arrest patients, conventional CPR is usually performed according to the American Heart 
Association CPR guidelines. This involves processes such as chest compressions, defibrillation, and 
administration of medications such as epinephrine. However, even when CPR is performed according 
to these guidelines, neurological outcomes are often poor due to ischemic brain injury caused by 
cardiac arrest.  
 
This study is an unproven clinical trial aiming to increase the rate of spontaneous circulation recovery 
by using REBOA during CPR to block the descending aortic blood flow, which directs blood flow to 
major organs. 
 
7. Expected side effects, risks, or discomfort for subjects 
The following side effects may occur in this study: 
 
Insertion-related vascular damage or aortic injury during the insertion process of the arterial sheath 
and REBOA may occur. To prevent this, the sheath and catheter will be inserted under ultrasound 
guidance using the Seldinger technique. REBOA will be inserted in a way that does not overlap with 
the chest compressions. Direct pressure will be applied to control bleeding if a hematoma occurs 
at the insertion site. 
 
8. Expected benefits for subjects 
REBOA is a procedure already being performed on trauma patients, and multiple animal experiments 
have shown improvements in hemodynamics in cardiac arrest patients. Considering previous 
research results, higher survival rates can be expected compared to performing conventional CPR 
alone. However, this study is an unproven clinical trial, so it is difficult to expect unconditional 
effectiveness.  
 
9. Alternative treatments (other available alternative treatments outside of the clinical trial) 
If not participating in this study, participants will receive standard CPR according to the 2020 
American Heart Association guidelines. This includes chest compressions at a rate of 100-120 per 
minute, defibrillation, prevention of hyperventilation, and the use of medications such as 
epinephrine. 
 
10. Injury and compensation 
During the clinical trial period, the medical staff will make every effort to ensure the safety of the 
patients and take prompt and appropriate actions to minimize any adverse reactions. In the event 
of harm occurring during this clinical trial, the principal investigator of the study will assume legal 
responsibility and provide compensation according to the provisions regarding compensation for 
harm. In the case of adverse reactions, the best possible treatment will be provided. 
 

11. Financial compensation 
No financial compensation is provided for participants.  
 
12. Expected costs 
The consumables used in this study, such as the REBOA catheter, will be supported by the research 
budget. Other than the REBOA, procedures performed are the same as procedures administered 
during conventional CPR, so there will be no additional costs incurred by participating in the study. 
 
13. Voluntary participation 
Participating in the clinical trial is entirely up to you. If you do not agree to participate, it will not 
be a problem. Even after agreeing to participate in the trial, you can withdraw consent at any time 
without any disadvantages. 
 
14. Provision of personal information 
During and after the completion of the clinical trial, the monitor, inspector, and other authorized 
personnel may directly access research-related data, including medical records, within the scope 
prescribed by regulations, to verify the procedural integrity and reliability. 
 
15. Confidentiality: 
All records regarding your personal information obtained during this research will be kept 
confidential and will not be disclosed to anyone else. Even if the research results are published, 
your personal information will remain confidential. 
 
16. Continuous Provision of Research-related Information: 
During this research, if the investigator becomes aware of any new facts or information that might 
influence your decision to continue participation, they will inform you or your representative of 
such facts or information. 
 
17. Contact Information: 
You or your representative may contact the following individuals for telephone consultations at 
any time: 
Person to consult regarding issues, concerns, or questions arising from the clinical trial: 
Principal Investigator: Professor Dong Keon Lee ☎031-787-7579 
Co-Investigator: Hee Eun Kim ☎031-787-7579 
Contact information for discussing issues, concerns, or questions related to the rights of research 
participants: 

IRB (Institutional Review Board) Support Office ☎031-787-8801~8806 
Clinical Research Ethics Center ☎031-787-88118813 
 
18. Termination of the Study: 
If any clinically significant adverse events occur during this clinical trial that are believed to be not 
beneficial to the patient, the patient may be withdrawn from the study. 
 
19. Expected Duration of the Participant's Clinical Trial: 
The anticipated duration of the participant's involvement in the clinical trial is one year, and they 
will be contacted by phone to assess their neurological prognosis after treatment completion. 
 
20. Number of Participants in the Clinical Trial: 
This is a multi-country, multi-center study. A total of 232 participants are expected to participate. 
Our institution plans to enroll 116 participants. 
 
21. Miscellaneous: 
If you decide to participate in the clinical trial, please fill in the provided consent form.  
 
 
 
 
 
 
 
 
 
 
 
 

Consent Form for Research Participants 
 
Title of the Study: Comparison of REBOA Use and Conventional CPR in Out-of-Hospital Cardiac 
Arrest Patients 
 
1. I have received a detailed explanation from the responsible physician regarding all 
information related to this research and have understood it sufficiently. 
2. I have also read the participant information sheet and understood its contents adequately, 
and I am aware that this research is being conducted for research purposes. 
3. My decision to participate in the research is voluntary, and I understand that I can refuse 
to continue participating or withdraw freely during the research period due to personal 
reasons or other factors, without receiving any medical or other disadvantages as a result. 
4. I am aware that if I experience harm due to adverse reactions caused by investigational 
medicinal products, the "compensation responsible party" will bear responsibility for 
compensation according to the provisions related to compensation. 
5. I understand that I may receive telephone contact for the purpose of investigating 
neurological prognosis up to one year after resuscitation, and I consent to the research 
accessing my contact information and personal details for research purposes only. 
6. I understand that I can contact the investigator at any time if I have any questions related 
to the research, and I agree to allow direct access to my medical records for research 
purposes only. 
 
Accordingly, I voluntarily agree to participate in this research according to my free will. 
Please sign and date below in your own handwriting. 
 
 
Name 
Signature 
Signed Date 
Participant 
 
 
YYYY / MM / DD 
Legal 
Representative  
 
 
YYYY / MM / DD 
Relationship with the Participant: ________________________   
Reasons for Proxy Signature ____________________________________________ 
Principal 
investigator  
 
 
YYYY / MM / DD 
 
If applicable, 
 
Name 
Signature 
Signed Date 
Observer 
 
 
YYYY / MM / DD 
 

  
1 
 
 
 
 
 
 
 
Seoul National University Bundang Hospital 
Informed Consent 
 
Effect Of Resuscitative Endovascular Balloon Occlusion of the Aorta in Non-Traumatic Out-of-
Hospital Cardiac Arrest (REBOA); A Multinational, Multicenter Randomized Controlled Trial 
 
Trial Registration Number: NCT06031623 
 
Current version number: Version 1.0 
Last updated date: September 17, 2023 
 
 
 
 

  
2 
Subject Information Sheet 
Subject Screening Number: ________________ 
 
Title of the Study: Effect Of Resuscitative Endovascular Balloon Occlusion of the Aorta in Non-
Traumatic Out-of-Hospital Cardiac Arrest (REBOA); A Multinational, Multicenter Randomized 
Controlled Trial 
 
Principal Investigator: Professor Dong Keon Lee, Department of Emergency Medicine, Bundang 
Seoul National University Hospital 
We kindly request your participation in this study.  
Before deciding to participate, it is important for you to fully understand why this study is being 
conducted and what your involvement will entail.  
The following information is provided to explain the details of this study, your role in it, and the 
process of the research. Please take sufficient time to read this subject information sheet, and if 
desired, discuss it with your family or others. Additionally, if you have any questions, please ask the 
exam coordinator or other study personnel, and carefully consider your decision to participate in 
this study. 
1. This study is conducted for research purposes.  
This clinical trial is not conducted for therapeutic purposes. It is a research study aimed at 
investigating the impact of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) 
during cardiopulmonary resuscitation on the prognosis of out-of-hospital cardiac arrest patients, 
with the goal of improving the prognosis of cardiac arrest patients. 
2. Background and Purpose of the Clinical Trial 
For out-of-hospital cardiac arrest (OHCA), cardiopulmonary resuscitation (CPR) is performed. 
However, even with high-quality CPR, the rate of return of spontaneous circulation (ROSC) is 
extremely low. The primary goal of CPR is to maintain sufficient blood flow to the brain and 
coronary arteries, preventing ischemic damage and correcting the reversible causes of cardiac arrest. 
However, even with effective chest compressions, only 30% of the pre-arrest blood flow to vital 
organs is achieved. This study aims to increase the rate of ROSC by using REBOA during CPR, which 
involves occluding the descending aorta to increase blood flow to major organs during 
resuscitation. 
3. Information on Investigational Drugs/Medical Devices and Randomization Probability 
This study will be conducted using randomization. The assignment to either the CPR group or the 

  
3 
REBOA group will be determined randomly based on a computer-generated randomization table, 
with an equal allocation ratio of 1:1. This study is a multinational study, with a total of 232 patients 
participating from Taiwan and Korea. If you agree to participate in the study, you will be randomly 
assigned to either the control or experimental group. 
 
4. Various Tests and Procedures that Subjects will Undergo in the Clinical Trial 
Both groups will receive CPR according to the 2020 American Heart Association guidelines for 
cardiopulmonary resuscitation. This standard CPR includes high-quality chest compressions at a rate 
of 100-120 per minute, prevention of hyperventilation, early defibrillation, and administration of 
medications such as epinephrine. 
After the randomization process, if assigned to the control group, you will receive standard CPR as 
described above.  
If assigned to the experimental group, in addition to the standard CPR 
according to the guidelines, femoral arterial access will be obtained, and a 
REBOA catheter will be inserted through the access. The catheter will be 
positioned within the aorta. The catheter will be inserted to an adequate 
length, and the balloon attached to the catheter will be positioned in the 
chest. Saline solution will be injected into the balloon to inflate it, 
obstructing the aorta, and preventing unnecessary blood flow to the lower 
body (Figure 1). Additionally, the catheter, arterial access, and other vital 
sign monitoring devices will be used to monitor hemodynamic parameters, 
including blood pressure, during CPR. If a return of spontaneous circulation 
is achieved, the REBOA will be removed after stabilization. 
 
Figure 1. Schematic diagram of REBOA 
 
The expected participation period for research subjects is one year, and they will be contacted by 
phone to measure neurological outcomes after treatment completion. 
 
5. Compliance requirements for research subjects 
There are no specific compliance requirements for research subjects. They may be contacted by 
phone to investigate neurological outcomes one year after resuscitation. Contact information for 
patients and caregivers will be collected for phone calls. 
 
 

  
4 
6. The fact that it is an unproven clinical trial 
In cardiac arrest patients, conventional CPR is usually performed according to the American Heart 
Association CPR guidelines. This involves processes such as chest compressions, defibrillation, and 
administration of medications such as epinephrine. However, even when CPR is performed 
according to these guidelines, neurological outcomes are often poor due to ischemic brain injury 
caused by cardiac arrest.  
 
This study is an unproven clinical trial aiming to increase the rate of spontaneous circulation 
recovery by using REBOA during CPR to block the descending aortic blood flow, which directs 
blood flow to major organs. 
 
7. Expected side effects, risks, or discomfort for subjects 
The following side effects may occur in this study: 
 
Insertion-related vascular damage or aortic injury during the insertion process of the arterial sheath 
and REBOA may occur. To prevent this, the sheath and catheter will be inserted under ultrasound 
guidance using the Seldinger technique. REBOA will be inserted in a way that does not overlap with 
the chest compressions. Direct pressure will be applied to control bleeding if a hematoma occurs at 
the insertion site. 
 
8. Expected benefits for subjects 
REBOA is a procedure already being performed on trauma patients, and multiple animal 
experiments have shown improvements in hemodynamics in cardiac arrest patients. Considering 
previous research results, higher survival rates can be expected compared to performing 
conventional CPR alone. However, this study is an unproven clinical trial, so it is difficult to expect 
unconditional effectiveness.  
 
9. Alternative treatments (other available alternative treatments outside of the clinical trial) 
If not participating in this study, participants will receive standard CPR according to the 2020 
American Heart Association guidelines. This includes chest compressions at a rate of 100-120 per 
minute, defibrillation, prevention of hyperventilation, and the use of medications such as 
epinephrine. 
 
10. Injury and compensation 
During the clinical trial period, the medical staff will make every effort to ensure the safety of the 
patients and take prompt and appropriate actions to minimize any adverse reactions. In the event 
of harm occurring during this clinical trial, the principal investigator of the study will assume legal 
responsibility and provide compensation according to the provisions regarding compensation for 
harm. In the case of adverse reactions, the best possible treatment will be provided. 

  
5 
11. Financial compensation 
No financial compensation is provided for participants.  
 
12. Expected costs 
The consumables used in this study, such as the REBOA catheter, will be supported by the research 
budget. Other than the REBOA, procedures performed are the same as procedures administered 
during conventional CPR, so there will be no additional costs incurred by participating in the study. 
 
13. Voluntary participation 
Participating in the clinical trial is entirely up to you. If you do not agree to participate, it will not be 
a problem. Even after agreeing to participate in the trial, you can withdraw consent at any time 
without any disadvantages. 
 
14. Provision of personal information 
During and after the completion of the clinical trial, the monitor, inspector, and other authorized 
personnel may directly access research-related data, including medical records, within the scope 
prescribed by regulations, to verify the procedural integrity and reliability. 
 
15. Confidentiality: 
All records regarding your personal information obtained during this research will be kept 
confidential and will not be disclosed to anyone else. Even if the research results are published, 
your personal information will remain confidential. 
 
16. Continuous Provision of Research-related Information: 
During this research, if the investigator becomes aware of any new facts or information that might 
influence your decision to continue participation, they will inform you or your representative of such 
facts or information. 
 
17. Contact Information: 
You or your representative may contact the following individuals for telephone consultations at any 
time: 
Person to consult regarding issues, concerns, or questions arising from the clinical trial: 
Principal Investigator: Professor Dong Keon Lee ☎031-787-7579 
Co-Investigator: Hee Eun Kim ☎031-787-7579 
Contact information for discussing issues, concerns, or questions related to the rights of research 
participants: 

  
6 
IRB (Institutional Review Board) Support Office ☎031-787-8801~8806 
Clinical Research Ethics Center ☎031-787-88118813 
 
18. Termination of the Study: 
If any clinically significant adverse events occur during this clinical trial that are believed to be not 
beneficial to the patient, the patient may be withdrawn from the study. 
 
19. Expected Duration of the Participant's Clinical Trial: 
The anticipated duration of the participant's involvement in the clinical trial is one year, and they 
will be contacted by phone to assess their neurological prognosis after treatment completion. 
 
20. Number of Participants in the Clinical Trial: 
This is a multi-country, multi-center study. A total of 232 participants are expected to participate. 
Our institution plans to enroll 116 participants. 
 
21. Miscellaneous: 
If you decide to participate in the clinical trial, please fill in the provided consent form.  
 
 
 
 
 
 
 
 
 
 
 
 

  
7 
Consent Form for Research Participants 
 
Title of the Study: Comparison of REBOA Use and Conventional CPR in Out-of-Hospital Cardiac 
Arrest Patients 
 
1. I have received a detailed explanation from the responsible physician regarding all 
information related to this research and have understood it sufficiently. 
2. I have also read the participant information sheet and understood its contents adequately, 
and I am aware that this research is being conducted for research purposes. 
3. My decision to participate in the research is voluntary, and I understand that I can refuse 
to continue participating or withdraw freely during the research period due to personal 
reasons or other factors, without receiving any medical or other disadvantages as a result. 
4. I am aware that if I experience harm due to adverse reactions caused by investigational 
medicinal products, the "compensation responsible party" will bear responsibility for 
compensation according to the provisions related to compensation. 
5. I understand that I may receive telephone contact for the purpose of investigating 
neurological prognosis up to one year after resuscitation, and I consent to the research 
accessing my contact information and personal details for research purposes only. 
6. I understand that I can contact the investigator at any time if I have any questions related 
to the research, and I agree to allow direct access to my medical records for research 
purposes only. 
 
Accordingly, I voluntarily agree to participate in this research according to my free will. 
Please sign and date below in your own handwriting. 
 
 
Name 
Signature 
Signed Date 
Participant 
 
 
YYYY / MM / DD 
Legal 
Representative  
 
 
YYYY / MM / DD 
Relationship with the Participant: ________________________   
Reasons for Proxy Signature ____________________________________________ 
Principal 
investigator  
 
 
YYYY / MM / DD 
 
If applicable, 
 
Name 
Signature 
Signed Date 
Observer 
 
 
YYYY / MM / DD 
 

 
 
 
 
 
 
Far Eastern Memorial Hospital 
Informed Consent 
 
Effect Of Resuscitative Endovascular Balloon Occlusion of the Aorta in Non-Traumatic Out-
of-Hospital Cardiac Arrest (REBOA); A Multinational, Multicenter Randomized Controlled 
Trial 
 
 
Trial Registration Number: NCT06031623 
 
Current version number: Version 1.0 
Last updated date: July 05, 2023 
 
 

Version 6 (Last Modified: 2023-07-05) 
1 
IRB approval date: 2023-07-15  
Far Eastern Memorial Hospital 
Informed Consent Form for Clinical Trials of Medical Devices 
Project Title: Resuscitative Endovascular Balloon occlusion of the Aorta in 
Patients with Non-Traumatic Out-of-Hospital Cardiac Arrest - An 
International Multi-center Randomized Clinical Trial 
Clinical Trial Institution: Far Eastern Memorial Hospital  
Commissioner: Jen-Tang Sun 
Project host: Jen-Tang Sun 
Position: Director of Surgical and Traumatic Emergency / Tel: 02-77281843 
Co-host: Chun-Yen Huang / Position:Attending physician / Tel: 02-77281843 
Co-host: Chih-Jung Chang / Position: Attending physician / Tel: 02-77281843 
Co-host: Sheng-En Chu / Position: Attending physician / Tel: 02-77281843 
Co-host: Yu-Chen Chiu / Position: Attending physician / Tel: 02-77281843 
Co-host: Fu-Chieh Hsieh / Position: Attending physician / Tel: 02-77281843 
※24-hour emergency contact: Jen-Tang Sun 
Tel: 0919-388100 
Name:  
Gender: 
Medical record number: 
You are cordially invited to participate in this clinical trial. This document provides you 
with pertinent information concerning the study. The lead investigator or an authorized 
representative will thoroughly explain the trial's objectives and address any inquiries you 
might have. Please ensure that all your questions are answered to your satisfaction before 
affixing your signature to this consent form. We understand the significance of such a 
decision, so we encourage you to reflect and deliberate before committing. Your signed 
consent is a prerequisite for participation in this trial. Should you choose to partake, this 
document will stand as an official record of your agreement. It's essential to note that even 

Version 6 (Last Modified: 2023-07-05) 
2 
IRB approval date: 2023-07-15  
after giving your consent, you retain the right to withdraw from the study at any point, with 
no need to furnish a reason. 
1. Status of the Medical Device Used in the Trial: 
Information on the Medical Device: 
The Resuscitative Endovascular Balloon Occlusion of the Aorta (commonly referred to 
as REBOA) is currently considered suitable for severe hemorrhaging below the diaphragm or 
even impending traumatic cardiac arrest (ITCA). It offers a minimally invasive, quick, and 
effective alternative surgery for bleeding control. This technique can halt hemorrhagic shock 
and prevent the exacerbation of metabolic issues, simultaneously providing patients with vital 
time, avoiding rushed, potentially unprepared invasive procedures like thoracotomy, 
laparotomy, or pelvic cavity tamponade in the emergency department. The method involves 
introducing a catheter into the aorta through a femoral approach and inflating a balloon near 
the bleeding site to temporarily halt blood flow, thereby increasing afterload to maintain 
cerebral and cardiac circulation. The aorta can be segmented into three zones: Zone I spans 
from the left subclavian artery to the celiac trunk, controlling major hemorrhage below the 
diaphragm; Zone III ranges from the renal arteries to the aortic bifurcation, managing major 
bleeding at the pelvis or lower limbs; Zone II, which is the region between Zones I and III, 
presently has limited applicability. Employing this technique can result in ischemia in organs 
distal to the balloon, potentially leading to complications such as visceral, spinal cord, and 
lower limb ischemia or reperfusion syndrome. Numerous studies on the use of REBOA in 
severe trauma patients have shown a 30-day survival rate of 59%. Traumatic cardiac arrest 
patients using REBOA to restore spontaneous circulation stand at 58.8%, with 40-41% 
reaching the operating room alive, and a 30-day survival rate between 5-10%. Beyond 
traumatic shock, REBOA is gradually being used for non-traumatic hemorrhage cases. 
According to Matsumura's study, common reasons for using REBOA include postoperative 
hemorrhage, ruptured aneurysm, gastrointestinal bleeding, and major postpartum 
hemorrhage. Although the mortality rate for these patients matches that of traumatic shock 
patients, the proportion of deaths due to bleeding is noticeably reduced. Far Eastern Memorial 
Hospital recorded two cases of aneurysm hemorrhage and two postpartum major hemorrhage 
cases. Among these, three had cardiac arrest, all of whom were resuscitated. One of the 
postpartum hemorrhage patients was successfully discharged with full neurological 
functionality. The team has published a case of ruptured aortic aneurysm treated with 

Version 6 (Last Modified: 2023-07-05) 
3 
IRB approval date: 2023-07-15  
REBOA in the Annals of Emergency Medicine. 
 
Market Status of the Medical Device: 
The device has received approval for marketing by the Taiwan Ministry of Health and 
Welfare and meets the indicated use of temporary vascular occlusion or dilation of artificial 
vessels (Health Ministry Medical Equipment Import No. 032086). 
2. Objective of the Study:  
Driven by our expertise in resuscitation for patients with Out-of-Hospital Cardiac Arrest 
(OHCA), and supported by positive evidence from past literature on the use of REBOA in 
OHCA patients, along with our team's extensive experience with REBOA, we aim to apply 
REBOA in the emergency management of OHCA patients. In our study, we explore the 
potential of using REBOA to assist with Advanced Cardiac Life Support (ACLS) in the 
hospital setting, an area less emphasized in many Western research studies that often 
prioritize pre-hospital care. We are proposing a three-year continuous project that will be a 
randomized controlled study across two international medical centers. Our research 
hypothesis posits that adult witnessed non-traumatic cardiac arrest patients, when aided with 
REBOA technique in conjunction with ACLS, as opposed to using ACLS alone, will exhibit 
better rates of return of spontaneous circulation, improved end-tidal carbon dioxide levels, 
higher non-invasive cerebral oxygenation levels, and patients will also display superior 
arterial perfusion, overall survival rates, and neurological prognosis. For this study within 
our country, we anticipate to include a control group of 58 patients and a REBOA group of 
58 patients, totaling 116 participants. 
3. Inclusion and Exclusion Criteria: 
Inclusion Criteria: 
(1)  Age between 20 and 80 years. 
(2)  Non-traumatic and non-hemorrhagic cause of the condition. 
(3)  Patients who experience witnessed cardiac and respiratory arrest between 9 am and 5 
pm from Monday to Friday and are brought to the emergency department. 
 

Version 6 (Last Modified: 2023-07-05) 
4 
IRB approval date: 2023-07-15  
Exclusion Criteria: 
(1) Patients or their representatives who have expressed refusal for resuscitation, either 
through a signed "Do Not Resuscitate" (DNR) order or an Advanced Care Planning 
(ACP) that explicitly states an opposition to emergency resuscitation efforts. 
(2) Patients who have already achieved ROSC before arrival to the emergency department. 
(3) Initiation of extracorporeal cardiopulmonary resuscitation. 
(4) Clinical identification of aortic conditions, such as aortic dissections or aneurysms, as 
evidenced by ultrasound results or a documented history. 
(5) Patients who were already severely neurologically impaired or in a vegetative state 
before the event. 
(6) Pregnant women 
4. Methodology & Procedures 
REBOA Group Procedure: 
The on-duty team treats the patient, including ACLS. Study-specific procedures are 
performed by research team physicians without affecting the original treatment. 
(1) The resuscitation process is performed and recorded by the on-duty emergency 
medical team. 
(2) Resuscitation following ACLS guidelines, including LUCAS treatment. 
(3) Secure airway establishment (endotracheal intubation) and monitor end-tidal CO2 
(EtCO2). 
(4) Research team personnel conduct ultrasonography to rule out contraindications. 
(5) Research team personnel insert femoral artery and central venous catheters to monitor 
arterial blood pressure and right atrial pressure. 
(6) Non-invasive cerebral oxygenation monitoring is set up by the research team. 
(7) Patient grouping (REBOA or Control) is determined using the Redcap system. 
(8) If assigned to the REBOA group, the research team places the REBOA between the 
left subclavian artery and the abdominal aorta main (Zone I), confirmed by 
transesophageal echocardiography, without interrupting CPR, and arterial pressure is 

Version 6 (Last Modified: 2023-07-05) 
5 
IRB approval date: 2023-07-15  
monitored. 
(9) Inflate the REBOA balloon with 20cc saline or until resistance is felt. 
(10) Continuous monitoring until the patient achieves Return of Spontaneous Circulation 
(ROSC) or is declared deceased. 
(11) Post-ROSC, the REBOA balloon is gradually deflated and removed. Post-resuscitation 
care is provided, and a cardiothoracic surgeon is consulted for arterial catheter removal 
evaluation. 
(12) Record patient details, physiological parameters, resuscitation measures, REBOA-
related info (attempts, insertion time, complications, CCF, and other ACLS quality 
indicators). 
(13) If the patient achieves sustained ROSC (more than 20 minutes), they sign a consent 
form. Tracking continues for 30 days post-enrollment or until death. Patient survival 
status and neurological outcomes are recorded. 
 
Control Group Procedure: 
The on-duty team treats the patient, including ACLS. Study-specific procedures are 
performed by the research team physicians without affecting the original treatment. 
(1) to  (6)  steps are similar to the REBOA group (from emergency procedure to cerebral 
oxygenation monitoring). 
(7) Group assignment is made using the Redcap system. 
(8) If assigned to the Control group, REBOA is not inserted.  
(9) Monitoring continues until the patient achieves ROSC or is declared deceased. 
(10) to  (11) steps are consistent with the REBOA group, focusing on ROSC achievement, 
post-resuscitation care, and consultation with a cardiothoracic surgeon. 
(12) to  (13) steps. Similarly, record patient details, parameters, resuscitation efforts, and 
monitor patient's health and neurological outcomes for 30 days post-enrollment or 
until death. 
5. Potential Risks, Occurrence Rates, and Management: 

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Risks Associated with the Medical Device Used in the Study: 
The complications may arise from the REBOA itself or during its placement process. 
These include but are not limited to: infections at the injury site or the onset of sepsis, 
allergic reactions, localized bleeding, vasospasms, endothelial injury, air embolism, pain and 
tenderness at the site of insertion, peripheral vascular ischemia, endocarditis, 
thrombocytopenia, myocardial infarction, blood clots leading to vascular obstruction, 
cerebral 
embolism, 
arteriovenous 
fistula, 
kidney-related 
complications, 
vascular 
complications (dissection, rupture, bleeding, or perforation), respiratory distress, or death. 
 
Risks Related to the Trial Procedure: 
The use of REBOA on eligible participants has been optimized to minimize risks, with 
every case being reviewed by a cardiothoracic surgeon. Despite this, there remains a 
possibility of participant death even after the standard resuscitation procedure. The primary 
responsibility of the cardiothoracic surgeon is to assist with the removal of the arterial 
catheter sheath and to be on standby in cases of difficulty with REBOA removal. 
6. Alternative Therapies and Explanation: 
Standard Advanced Cardiac Life Support (ACLS) without the placement of REBOA. 
7. Anticipated Benefits of the Trial: 
The trial aims to increase coronary and cerebral perfusion in participants. In cases where 
aggressive treatments (such as ECMO) are not applicable, it hopes to enhance the chances of 
participants achieving return of spontaneous breathing and circulation, as well as improving 
neurological outcomes. 
8. The Contraindications, Limitations, and Requirements for 
Participants During the Trial: 
None 
9. Confidentiality of Participants' Personal Information: 
The system data is maintained by a dedicated research assistant, ensuring confidentiality 

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of all relevant information. The project leader takes meticulous steps to protect the collected 
documents and complies with the "Personal Data Protection Act" and other related 
regulations. Initially, the data will be labeled with the participant's name and medical record 
number. The participants will then be coded. Once the subsequent medical record data 
collection is completed (within 30 days), the names of the participants will be removed, 
leaving only the code. All case data will be archived on the research computers of both the 
lead and co-investigators. 
After undergoing research coding management, the analyzed data completely omits 
personal identifiers such as national identification numbers, home phone numbers, 
addresses, etc., making it impossible to trace the patient's identity, ensuring the privacy of 
the subjects. Collected hard copies and multimedia data will be stored on the assistant's 
computer. The lead investigator will personally analyze them, or research members will 
analyze them on the computer under the supervision of the lead investigator. 
10. Withdrawal and Termination of the Trial: 
You are free to decide whether to participate in this trial. You can also withdraw your 
consent and leave the trial at any time, without providing any reason. This decision will not 
result in any inconvenience and will not affect the future medical care provided to you by 
your physician. The trial's lead investigator may also choose to terminate the trial if deemed 
necessary. 
11. Medical Care, Compensation, and Insurance: 
(1) If you participate in this clinical trial and sustain damage due to an adverse reaction, 
our hospital will bear the responsibility for compensation. However, anticipated 
adverse reactions, side effects, or risks noted in this consent form will not be 
compensated. 
(2) If you participate in this clinical trial and experience an adverse reaction or damage, 
our hospital and the lead investigator are committed to providing professional 
medical care and consultation. You will not be responsible for the necessary medical 
expenses associated with treating the adverse reaction or damage. 
(3) Aside from the aforementioned compensation and medical care, this trial does not 
offer any other form of compensation. If you are unwilling to accept these risks, 

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please refrain from participating in the trial. 
(4) Signing this consent form will not deprive you of any legal rights. 
(5) This trial does not have liability insurance. 
12. Preservation, Use, and Reuse of Participant's Specimens (and 
their derivatives) and Personal Information: 
The collected data will be coded and stored on the computers of the lead and co-
investigators, managed by the aforementioned personnel. Only the participant's code will be 
displayed on the collected data. Additionally, all data gathered during this study, including 
paper records and video recordings, will be destroyed within 3 years after the conclusion of 
the study. 
13. Rights of the Participant: 
(1) There will be no charges related to this study imposed on you, and this trial is not 
covered under the National Health Insurance scope. 
(2) Any significant findings related to your health or illness that may affect your 
willingness to continue participating in the clinical trial will be promptly 
communicated to you. 
 
(3) If you have questions about the nature of the trial or concerns about your rights as a 
participant, or if you suspect any harm as a result of participating in the trial, you can 
contact the Institutional Review Board (IRB) of our hospital for consultation at 02- 
89667000, extension 2152. Alternatively, you can contact the Participant Protection 
Center at 02-89667000, extension 2546. 
(4) To proceed with the trial, you must be under the care of the physicians involved in 
this research. After being admitted to the Intensive Care Unit (ICU), you will be 
cared for by the ICU physicians. If you have any concerns or issues now or during the 
trial, please feel free to contact Dr. Sun Ren-Tang from the Emergency Medicine 
Department at Far Eastern Memorial Hospital, available 24/7 at 0919-388100. 
(5) Two copies of this consent form have been provided, one of which has been handed 
to you. The physician has explained the nature and objectives of this trial in full and 

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has answered all your questions concerning the medical equipment and trial 
procedures. 
14. Signature: 
The principal investigator or their authorized personnel has explained in detail the 
nature, purpose, potential risks, and benefits of the trial method mentioned in this 
clinical trial. 
□Principal Investigator/□Co-Investigator/□Authorized Research Personnel 
Signature: _____________ 
Date: ____Year____Month____Day 
 
I have fully understood the aforementioned trial method, its potential risks and 
benefits. Any questions about this trial have been thoroughly explained by the 
research team. I voluntarily agree to become a participant in this clinical trial. 
Participant's Signature: _____________ 
Date: ____Year____Month____Day 
 
Legal Representative/Person with Consent Authority Signature: _____________ 
Date: ____Year____Month____Day 
Relationship to Participant: □Spouse, □Adult Child, □Parent, □Sibling, □Grandparent 
 
＊ If the participant is a teenager aged 7 to 20 with limited legal capacity, both the 
participant and the legal representative should sign. 
＊ The legal representative should also present relevant identification documents for the 
principal investigator to verify their identity. 
＊ Even if the participant is not legally incapacitated or has restricted capacity, should 
they exhibit signs of confusion, mental, or cognitive impairments that prevent effective 
communication and sound judgment, a person authorized to provide consent can act 
on their behalf. When proceeding to sign the consent form, the authorized person must 

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present relevant identification documents to allow the principal investigator to 
validate their identity. 
＊ For written consents provided by the aforementioned relatives or authorized persons, 
a single person's signature suffices. In the event of conflicting opinions among these 
individuals, priority is determined by the predefined sequence, as indicated in the 
aforementioned order. Within the same category of relationship, closer kinship takes 
precedence. If kinship level is identical, cohabitating family members are given 
priority. In the absence of cohabitating relatives, the elder individual's decision takes 
precedence. 
 
Witness 1. Signature: _____________ 
Date: ____Year____Month____Day 
ID Number: 
Address: 
Contact Number: 
 
Witness 2. Signature: _____________ 
Date: ____Year____Month____Day 
ID Number: 
Address: 
Contact Number: 
 
＊ If the participant, legal representative, or person with the right to consent is illiterate, 
a witness should be present throughout all discussions related to the consent form. 
After ensuring that the consent of the participant, legal representative, or person with 
the right to consent is given voluntarily, they should sign the consent form and record 
the date. Research-related personnel cannot act as witnesses.