Effect of Vasopressin, Steroid, and Epinephrine Treatment in Patients With Out-of-hospital Cardiac Arrest

Study Overview
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Brief Summary
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Steroid use could be considered for patients with weaker adrenal function among those with post-cardiac arrest (CA) return of spontaneous circulation (ROSC), according to the former study. This finding is consistent with the medical background of this present study. This study will be the first to investigate these additional drugs of injection and associated prognosis in cardiac arrest (CA) patients outside the hospital, providing significant basic data.

Detailed Description
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In South Korea, approximately 20,000 patients are found to experience cardiac arrest (CA) annually, with a reported survival rate of approximately 4.8% (2015). In patients who are resuscitated from cardiac arrest (CA), neurological prognosis is assessed based on whether the patient can independently perform a daily routine after leaving the hospital. It is an essential issue for patients, as well as their families and local communities. In this sense, research interest in achieving a good neurological prognosis in post-discharge cardiac arrest (CA) patients is increasing. The neurologic status of post-cardiac arrest (CA) patients, who are being considered for discharge from the hospital, is examined mostly using the Cerebral Performance Category (CPC) score, with a score of 1 or 2, on a scale of 1 to 5, indicative of good neurological status. Several previous South Korean studies have compared treatments using epinephrine only with those using epinephrine, vasopressin, and steroid during cardiopulmonary resuscitation (CPR) of cardiac arrest (CA)patients in the hospital. The vasopressin-steroid-epinephrine (VSE) group was reported to show a better return of spontaneous circulation (ROSC), lower whole-body inflammatory reaction, less cases of organ failure, and more cases of survival and hospital leave while showing better results of neurological prognosis. However, studies are lacking on treatment of cardiac arrest (CA) cases outside the hospital. In addition, because the three drugs of the vasopressin-steroid-epinephrine (VSE) regimen are used together, it is hard to identify which of them is most effective. Investigators are implementing a multicenter, prospective study to compare the use of vasopressin, steroid, and both vasopressin and steroid in post-cardiac arrest (CA) patients outside the hospital and examine the effects on ROSC and neurological score in this population. No South Korean study has been conducted on additional drugs of injection, other than epinephrine, in cardiac arrest (CA) treatment. In one study, steroid use in post-cardiac arrest (CA) patients with return of spontaneous circulation (ROSC) was investigated by examining the levels of blood cortisol and adrenal corticotropic hormone. The researchers found that patients showing relatively poorer results in the exams recorded lower. Therefore, steroid use could be considered for patients with weaker adrenal function among those with post-cardiac arrest (CA) return of spontaneous circulation (ROSC), according to the study. This finding is consistent with the medical background of this present study. It is possible that steroid use not only assists the adrenal function in post-cardiac arrest (CA) patients but also positively influences their spontaneous circulation recovery and neurological prognosis. However, this research is also the result of a single-organizational retrospective study. To establish additional corresponding experiences, a multicenter prospective investigation is deemed necessary. As previously mentioned, several studies involving in-hospital cardiac arrest (CA) patients have been conducted. The present study will be the first to investigate these additional drugs of injection and associated prognosis in cardiac arrest (CA) patients outside the hospital, providing significant basic data.

Official Title
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Comparison of the Effect of Vasopressin, Steroid, and Epinephrine Treatment in Patients With Out-of-hospital Cardiac Arrest: Multi-center, Double Blind, Randomized, Placebo-controlled Study

Conditions
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Cardiac Arrest

Intervention / Treatment
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* Drug: Control Group
* Drug: Experimental Group 1
* Drug: Experimental Group 2
* Drug: Experimental Group 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The group of patients who participated in the study included adults aged at least 19 years among the atraumatic CA outpatients who came to the ER and received CPR. Exclusion Criteria: Pregnant women and young children aged <18 years; Patients with underlying disease cases without the possibility of resuscitation (e.g., terminal cancer); Patients with do-not-resuscitate (DNR) status; Death by excessive bleeding (e.g., abdominal main artery rupture); Patients who have experienced in-hospital CA; Patients previously treated with steroid, anti-cancer medicine, or immunosuppression treatment before CA; Patients already been registered with other studies; or Patients from whom informed consent cannot be obtained

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Group<br>Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) only Control group receives intravenous injection of 1 mg epinephrine every cycle (about 3 minutes) during CPR and uses syringe No. 1, 5 times (every 3 minutes), and syringe No. 2, one time (in the first cycle). After each injection, inject 10 mL saline solution additionally. Syringe No. 1 : Saline solution Syringe No. 2 : Saline solution | Drug: Control Group<br>* Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) only<br>* Other names: Epinephrine;|
| Active Comparator: Experimental Group 1<br>Using Vasopressin [20 IU/CPR cycle] injection until the 5th cycle Experimental Group 1 receives intravenous injection of 1 mg epinephrine every cycle (about 3 minutes) during CPR and uses syringe No. 1, 5 times (every 3 minutes), and syringe No. 2, one time (in the first cycle). After each injection, inject 10 mL saline solution additionally. Syringe No. 1 : Vasopressin Syringe No. 2 : Saline solution | Drug: Experimental Group 1<br>* Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) and Vasopressin(20 international unit(IU)/cardiopulmonary resuscitation(CPR) cycle)<br>* Other names: Epinephrine + Vasopressin;|
| Active Comparator: Experimental Group 2<br>Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) and Steroid(Methylprednisolone, 40 mg at first cycle) Experimental Group 2 receives intravenous injection of 1 mg epinephrine every cycle (about 3 minutes) during CPR and uses syringe No. 1, 5 times (every 3 minutes), and syringe No. 2, one time (in the first cycle). After each injection, inject 10 mL saline solution additionally. Syringe No. 1 : Saline solution Syringe No. 2 : Steroid | Drug: Experimental Group 2<br>* Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) and Steroid(Methylprednisolone, 40 mg at first cycle)<br>* Other names: Epinephrine + Steroid;|
| Experimental: Experimental Group 3<br>Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle), Vasopressin(20 international unit(IU)/cardiopulmonary resuscitation(CPR) cycle) and Steroid(Methylprednisolone, 40 mg at first cycle) Experimental Group 3 receives intravenous injection of 1 mg epinephrine every cycle (about 3 minutes) during CPR and uses syringe No. 1, 5 times (every 3 minutes), and syringe No. 2, one time (in the first cycle). After each injection, inject 10 mL saline solution additionally. Syringe No. 1 : Vasopressin Syringe No. 2 : Steroid | Drug: Experimental Group 3<br>* Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle), Vasopressin(20 international unit(IU)/cardiopulmonary resuscitation(CPR) cycle) and Steroid(Methylprednisolone, 40 mg at first cycle)<br>* Other names: Epinephrine + Vasopressin + Steroid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examined for neurological prognosis of each group | - main result variables: survival discharge with good CPC (CPC 1 or 2) | survival discharge, through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examined for return of spontaneous circulation (ROSC) status | sustained ROSC (more than 20mins) | ROSC, up to 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Out-of-Hospital Cardiac Arrest, Vasopressin-steroid-epinephrine (VSE), Treatment Outcome, prognosis, Return of spontaneous circulation