Clinical Research Directory

Neuroprotective Effect of Remote Ischemic Post-conditioning in Out-of-hospital Cardiac Arrest

Patients admitted to intensive care unit (ICU) following an out-of-hospital cardiac arrest (OHCA) have a high morbidity and mortality rate, primarily due to ischemia-reperfusion (I/R) syndrome leading to anoxic-ischemic brain injury. Despite current recommended advanced life support therapies, no specific treatment or procedure has yet been shown to improve the neurological outcome of such patients. Remote ischemic post-conditioning (RIPOST) which usually consists of applying brief and repeated cycles of ischemia alternating with reperfusion by inflating and deflating a blood pressure cuff or a pneumatic tourniquet placed around a limb, is a promising strategy to protect organs against I/R injury, including brain. Regarding cardiac arrest, pre-clinical studies have demonstrated an improvement in neurological outcome in animal subjects treated with RIPOST after cardiopulmonary resuscitation. The aim of our study is to demonstrate the benefit of early RIPOST in OHCA patients in reducing neurological injury and organ failure related to I/R syndrome.

Emergency Resuscitative Endovascular Balloon Occlusion of the Aorta in Out of Hospital Cardiac Arrest

This study will assess the feasibility of performing pre-hospital resuscitative endovascular balloon occlusion of the aorta (REBOA) as an adjunct to conventional Advanced Life Support (ALS) in patients suffering from non-traumatic out of hospital cardiac arrest (OHCA). As well as providing valuable insights into the technical feasibility of performing this procedure as part of a resuscitation attempt, the study will also document the beneficial physiological effects of REBOA in this group of patients.

The Validation and Development of Termination-of-Resuscitation (TOR) Rules in OHCA Patients in Asia Countries

Objectives/Hypotheses 1. Prehospital termination-of-resuscitation (TOR) rules were developed in North American and European sites. Whether they remained valid in different geographic, ethnic, and cultural background areas is still under debate. 2. Differences in characteristics of out-of-hospital cardiac arrests (OHCAs) and configurations of emergency medical service (EMS) between the Western and Asian countries, including relatively lower rate of presenting shockable rhythm (i.e. ventricular fibrillation / ventricular tachycardia; VF/VT), lower rates of bystander CPR, less advanced life support (ALS) implementation, and less public access defibrillators, might create potential threats to the prediction accuracy of TOR rules. 3. We aim to conduct a study to validate the performance of ever published TOR rules in Asian OHCA population, including non-traumatic, traumatic, and pediatric OHCA patients. Furthermore, assess the possible variables that may impact the performance of TOR rules. 4. We also aim to develop new TOR rules based on PAROS registry for Asia population, focusing on non-traumatic, traumatic, and pediatric OHCA patients, respectively.

PRE-hospital Cooling to improvE carDiac arrEst Neurological outComEs (PRECEDENCE)

The PRE-hospital Cooling to improvE carDiac arrEst Neurological outComEs (PRECEDENCE) study is a pilot feasibility trial evaluating the implementation of pre-hospital targeted temperature management (TTM) using a wearable surface cooling device (CarbonCool® vest) in adult out-of-hospital cardiac arrest (OHCA) patients with return of spontaneous circulation (ROSC). The study aims to assess feasibility, fidelity, acceptability, and safety of initiating cooling in the field by emergency medical services (EMS) prior to hospital arrival. Results will inform the design of a larger definitive trial to determine the clinical effectiveness of early pre-hospital TTM in improving neurological outcomes.

Enhanced Community First Responder System Evaluation in Singapore

The rise in out-of-hospital cardiac arrest (OHCA) cases in Singapore highlights the need for effective bystander cardiopulmonary resuscitation (BCPR). Despite many lay responders performing CPR, survival rates with good neurological outcomes have not significantly improved, prompting research into the quality of CPR as a critical factor. The study by Gallagher EJ et al. showed a significant survival improvement with high-quality CPR. To address this, the Unit of Pre-hospital and Emergency Research (UPEC) trained thousands of community first responders (CFRs) in simplified CPR techniques using hands-only and DA-CPR methods. A significant innovation is the CPRcard®, developed by Laerdal in Norway, which offers real-time feedback on the quality of chest compressions. However, only 36% of CFRs using the CPRcard® achieved the desired compression standards, indicating room for improvement. The study proposes enhancing CFR support with information communication technology (ICT), enabling two-way audio and one-way video communication between CFRs and dispatchers. This aims to reduce stress among responders, increase their willingness to engage with OHCA alerts, and improve CPR quality. The clinical trial in Singapore will compare the current system against the enhanced CFR support system (eCSS), focusing on the real-time relay of CPR performance data, communication ease, and implementation factors. The high-quality CFR and OHCA registries in Singapore provide a robust setting for this research, aiming to enhance CPR delivery and improve OHCA outcomes through technology and real-time support.

The Effect of Prehospital Combination of Epinephrine, Vasopressin, and Steroid in OHCA

This project is a randomized controlled clinical research design, The hypothesis P-I-C-O of the study is: For adult patients in the Taipei City and New Taipei City communities who have suffered sudden non-traumatic death and have been resuscitated by advanced paramedics, the intervention group that receives combined drug treatment (epinephrine, vasopressin, methylprednisolone) has a better rate of sustained recovery of spontaneous circulation (ROSC) (primary outcome) and long-term survival status (secondary outcomes) compared to the control group that receives single drug treatment (epinephrine).

Frontal EEG in OHCA Feasibility Study

This study aims to optimize the treatment of out-of-hospital cardiac arrest (OHCA) by focusing on neurological outcomes through Bispectral Index (BIS) monitoring. It will evaluate the feasibility of BIS monitoring in the prehospital phase, assess the need for sedation based on BIS values, and examine the timing of interventions in ICU (intensive care unit) settings to identify irreversible Hypoxic-Ischemic Brain Injury (HIBI).

Relevance of Reversible Causes During OHCA (Rebecca Study)

Management of the reversible causes in cardiac arrest is fundamental for successful treatment of out-of-hospital cardiac arrests. Point-of-care diagnostics as prehospital emergency ultrasound, blood gas analysis and toxicological screening support the diagnostic process of evaluating potential reversible causes. Digital tools provide support of a structured approach. This study aims to evaluate the frequency of reversible causes during OHCA as well as specific interventions due to these findings. Furthermore, CPR performance (hands-off, ROSC, 30-day mortality) and cognitive load of the prehospital emergency physician will be investigated. In total 100 patients with OHCA will be included in this study. Identification of reversible causes will be performed upon a structured protocol using an interactive checklist. Cognitive load of emergency physician as well as CPR parameter (frequency of reversible causes, hands-off, ROSC, 30-day mortality) will be analysed.

Prehospital Resuscitation Intranasal Cooling Effectiveness Survival Study 2

The aim of this clinical trial is to study the impact of ultra-early transnasal evaporative cooling after cardiac arrest and subsequent hypothermia at hospital, on survival with complete neurologic recovery, compared to currently recommended normothermia. The study population will consist of patients 18-79 years old, with out-of-hospital cardiac arrest with initial shockable rhythm. The main research question it aims to answer is whether there is a difference in survival with complete neurologic recovery at 90 days after cardiac arrest between the group of patients that received ultra-early cooling, compared to the group that was treated with normothermia. Participants will be randomized to two groups. One group (the intervention group) will receive ultra-early trans-nasal evaporative cooling initiated by EMS personnel at the scene of the cardiac arrest, and subsequent systemic hypothermia for 24 hours at hospital arrival. The other group (the control group), will receive standard of care (advanced cardiac life support and normal body temperature (normothermia)).

The Development of the Simulation Curriculum and AI-incorporated Assessment Tool for Transesophageal Echocardiography

This study aims to establish a novel transesophageal echocardiography (TEE) simulation curriculum based on previous research results and suggestions from the American College of Emergency Physicians. To better evaluate the efficacy of the curriculum, an evaluation model utilizing artificial intelligence (AI) would be introduced. The study population is at least 60 junior physicians in the emergency department or other departments interested in TEE. After the curriculum, junior physicians could utilize TEE on cardiac arrest patients and improve diagnostic accuracy and patient outcomes.

The PulsePoint Study

This randomized controlled trial will evaluate whether use of the PulsePoint system increases bystander CPR or defibrillator use compared to standard dispatch procedures in patients who suffer non-traumatic, out-of-hospital cardiac arrest in a public location. Half of all suspected cardiac arrest 9-1-1 calls in a public location will receive PulsePoint alerts (treatment arm). The other half of this eligible patient cohort will receive standard dispatch procedures (control arm).

Technological and Patient-tailored Innovations for Maximizing Effectiveness of Cardiac Arrest Resuscitation

Out-of-hospital cardiac arrest (OHCA) affects 275,000 people in Europe every year. In Italy alone, 50,000 people experience OHCA annually, with only 9% surviving. Half of the survivors suffer severe brain damage. Immediate CPR and defibrillation by bystanders before the ambulance arrives can save lives, but often, CPR starts only when the ambulance gets there. Additionally, half of all OHCAs occur when the person is alone, causing delays in recognizing the emergency, calling for help, and starting lifesaving actions. Effective chest compressions and defibrillation are crucial but are often not done correctly or are not customized for each patient. Current guidelines recommend the same approach for everyone, which doesn't consider individual needs. To tackle these issues, we plan to develop artificial intelligence (AI) algorithms, smartphone apps, and new devices. Our main goal is to create tools and technologies to improve the recognition of OHCA and provide timely and effective interventions, ultimately reducing the impact of OHCA and improving survival rates. First, we aim to create an AI algorithm that can predict major cardiovascular events like heart attacks or cardiac arrests minutes, hours, or days before they happen. We will collect data from wearable devices to train and validate this algorithm, helping us identify individuals at risk. By alerting these individuals, they can seek emergency care and receive treatment before a cardiac arrest occurs. We will also work on recognizing OHCA cases from surveillance camera footage when they happen to people who are alone. Second, to increase the rate of CPR and defibrillation before ambulances arrive, we will develop a smartphone app that geolocates and alerts nearby citizens to act as first responders. The app will guide them on how to quickly find a defibrillator and use it. Third, to find the best spots on the chest for compressions and defibrillation, we will study chest scans from CTs and echocardiograms in both elective patients and cardiac arrest victims. This will help us understand the effects of compressing different heart structures and develop a sensor to determine the optimal positions for compressions and defibrillator pads. Our multidisciplinary team of clinicians, researchers, and engineers will conduct experimental, simulation, and observational studies to develop these technologies, evaluate their potential for patents, design a plan for their use, and test their effectiveness in preventing and recognizing OHCA. We believe that by improving each step in the chain of survival-preventing cardiac events, early recognition, timely CPR and defibrillation, and high-quality advanced resuscitation-we can significantly improve treatment times and reduce the global death and disability rates caused by OHCA.

Initial Double Sequential External Defibrillation in Out of Hospital Cardiac Arrest

Double Sequential External Defibrillation (DSED) represents an alternative treatment of refractory ventricular fibrillation (rVF) in out-of-hospital cardiac arrest (OHCA). The procedure consists of two defibrillators that administer shocks at the same time. Currently, the procedure is not initiated before at least three failed attempts with one defibrillator. This can delay the potential benefits of establishing DSED earlier in the treatment. Studies have shown that early defibrillation is crucial for survival in OHCA patients, and in 2022, a clinical trial showed that survival in patients treated with DSED was higher compared to standard treatment. The effect of initiating OHCA treatment is unknown. The DUALDEFIB trial seeks to investigate if treating OHCA patients with DSED as an initial treatment will increase survival and provide improved neurological outcome.

Impact of Early Antibiotics on Non-Traumatic Out of Hospital Cardiac Arrest (OHCA)

Specific Aim : The specific aim is to conduct a randomized prospective clinical trial to determine whether no antibiotics in OHCA patients in the ED with very low likelihood of infection is non-inferior to early antibiotic treatment. Hypothesis a: 28-day all-cause mortality will be non-inferior in OHCA patients with very low likelihood of infection who do not receive antibiotic therapy compared with those who receive early antibiotic therapy Hypothesis b: There will be no difference in subsequent incidence of proven infections in the no antibiotics vs, early antibiotics groups Hypothesis c: There will be no difference in the length of ICU stay and overall hospital stay in the early antibiotics vs. no antibiotics groups

Wroclaw Out-Of-Hospital Cardiac Arrest Registry

The purpose of this study is to assess the efficacy of institutionalized care program of patients with out-of-hospital cardiac arrest.

NFL Dynamics as a Predictor Factor in Patients With Out of Hospital Cardiac Arrest

To investigate the pharmacodynamics of light chain of NFL in patients with out-of hospital cardiac arrest after successful resuscitation and determine the difference in the serum levels of NFL in patients with favorable neurological outcome compared to those with non-favorable neurological outcome.

Compression Only CPR Versus Standard CPR in Out-Of-Hospital Cardiac Arrest - A Randomized Survival Study

Out-of-hospital cardiac arrest (OHCA) is one of the leading causes of mortality in the industrialized world. Bystander CPR before arrival of the Emergency Medical Service (EMS) is associated with an increased chance of survival. During the last decade, the best form of bystander CPR has been debated. Chest Compression Only CPR (CO-CPR) has been advocated as a preferable method in situations where the bystander has no previous knowledge in CPR, both because its believed to be equally efficient but also a simplified form of CPR that could lead to a higher incidence of bystander-CPR. In an initiative to increase CPR rates the American Heart Association has launched public campaigns such as the "hands-only CPR" promoting CO-CPR as an option to S-CPR for adult non-asphyxic cardiac arrest. In the 2015 updates of the European resuscitation council guidelines it states that the confidence in the equivalence between the two methods is not sufficient to change current practice. Whether CO-CPR leads to a survival rate no worse than, equally effective, or even superior to standard CPR in situations where the bystander has previous CPR training however remains unclear. This clinical question remains unanswered while millions of people are trained in CPR worldwide each year. The overall purpose with this research project is to investigate whether instructions to perform a simplified form of CPR consisting of compressions only (CO-CPR) to bystanders with prior CPR-training is non-inferior, or better than, standard CPR (S- CPR) in witnessed Out-of-Hospital Cardiac Arrest (OHCA).

Systemic Evaluation of the Etiologies of Young Adults With Non-traumatic Out-of-hospital Cardiac Arrest

The goal of this observational study is to establish the protocol of systemic analysis of the causes of non-traumatic cardiac arrest in young patients. The main questions it aims to answer are: * Whether the protocolized classification of cardiac arrest minimizes the proportion of unknown causes and mis-classification in young cardiac arrest patients? * Whether the incorporation of genetic tests in the identification protocol of arrest cause helps the recognition of sudden arrhythmic death syndrome in young cardiac arrest patients? Participants will be asked to received serial examinations including genetic analysis to explore the cause of cardiac arrest.

REmote COnditioning in Out-of-Hospital Cardiac Arrest

Out-of-Hospital Cardiac Arrest remains a major public health problem, resulting in high mortality largely related to multiple organ failure and poor neurological outcomes due to brain anoxia. The pathophysiology of organ dysfunction after resuscitated out-of-hospital cardiac arrest involves ischemia-reperfusion processes. Remote ischemic conditioning is a therapeutic strategy used to protect organs against the detrimental effects of ischemia-reperfusion injury. The objective of the present trial is to determine whether remote ischemic conditioning performed early after out-of-hospital cardiac arrest can decrease mortality, or multiple organ failure and/or severe neurological failure.

The OSIRIS ECPR Trial

The OSIRIS trial is an investigator-initiated, multicenter, multinational, open-label, randomized controlled trial with a 2:1 concealed allocation of refractory out-of-hospital cardiac arrest (OHCA) patients to the extracorporeal cardiopulmonary resuscitation (ECPR) based approach versus the conventional cardiopulmonary resuscitation (CCPR) approach.

A Danish ICD-study in Patients with Coronary Artery Disease Resuscitated from Ventricular Fibrillation

DanICD is a randomized, controlled study to with the aim to assess whether there is a benefit of ICD-implantation in patients with coronary artery disease (including acute myocardial infarction), who survive cardiac arrest due to ventricular fibrillation/sustained ventricular tachycardia and undergo revascularization and with an LVEF above 35%.

The Danish Out-of-Hospital Cardiac Arrest Study

After resuscitation from Out-of-Hospital Cardiac Arrest (OHCA) patients experience Post Cardiac Arrest Syndrome due to ischemia and reperfusion injury. It consists of systemic inflammation, cerebral and myocardial dysfunction, and the condition that led to the arrest. Most OHCA patients will receive critical care intubated in an Intensive Care Unit (ICU). Despite this \~50% die; mainly due to brain injury. Several targets can be considered for improving outcomes. To dampen systemic inflammation and optimize cerebral perfusion seem important. Deep sedation has been required for targeted temperature management (TTM) but may also be brain protective. After end of sedation, many patients have some cerebral dysfunction that may facilitate delirium. The aim of this trial is therefore to improve treatment of comatose OHCA patients by evaluating 4 interventions in a factorial design addressing each of these targets in a randomized clinical trial: 1. Systemic inflammation: Anti-inflammatory treatment with high dose steroids (dexamethasone) or placebo. 2. Cerebral perfusion: Backrest elevation during sedation at 5 or 35 degrees. 3. Duration of sedation: Early wakeup call and potential extubation at ≤6 hours after admission or later as current standard practice at 28-36 hours. 4. Delirium: Prophylactic treatment with anti-psychotic medication (olanzapine) or placebo. The trial is designed as a phase III trial, randomizing 1000 patients at Danish cardiac arrest centers. The primary endpoint is 90 days all-cause mortality for the interventions targeting systemic inflammation and cerebral perfusion, while it is days alive outside of hospital within 30 days for the interventions concerning duration of sedation and delirium. The trial has potential to improve outcomes for comatose OHCA patients - a group with a grave prognosis with currently only limited evidence-based treatments.

Automatic Ventilation in Prehospital Resuscitation on OHCA

The goal of this randomized controlled trial is to compare prehospital ventilation strategies in out-of-hospital cardiac arrest. The intervention group is automatic ventilation and the control group is manual ventilation. The main questions it aims to answer are: 1. How does automatic ventilation affect OHCA patients' survival and prognosis comparing to manual ventilation. 2. What are the differences on resuscitation qualities between automatic ventilation and manual ventilation.

Accuracy of EEG Slow Wave Activity in Predicting Favourable Outcome in Patients With Hypoxic Brain Injury - A Substudy of STEPCARE Trial

This is an observational substudy embedded in the STEPCARE Trial. The study involves EEG analysis, covered by the ethics approval of STEPCARE Trial. The investigators aim to compare the accuracy of a continuously measured algorithm-based EEG index, C-Trend Index, with retrospective visual analysis of continuous EEG in predicting favorable functional outcome in adult patients treated in intensive care units after out-of-hospital cardiac arrest. The primary hypothesis is that the accuracy of C-Trend Index has at least 10% better accuracy in predicting favorable outcome than the visual analysis of cEEG, when assessed early, 9-12 hours after return of spontaneous circulation (ROSC).