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

Primary Purpose

Cardiac Arrest

Status
Unknown status
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Control Group
Experimental Group 1
Experimental Group 2
Experimental Group 3
Sponsored by
Korea University Guro Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiac Arrest focused on measuring Out-of-Hospital Cardiac Arrest, Vasopressin-steroid-epinephrine (VSE), Treatment Outcome, prognosis, Return of spontaneous circulation

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Korea University Guro HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Experimental

Arm Label

Control Group

Experimental Group 1

Experimental Group 2

Experimental Group 3

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

Examined for neurological prognosis of each group
- main result variables: survival discharge with good CPC (CPC 1 or 2)

Secondary Outcome Measures

Examined for return of spontaneous circulation (ROSC) status
sustained ROSC (more than 20mins)

Full Information

First Posted
October 4, 2017
Last Updated
October 17, 2017
Sponsor
Korea University Guro Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03317197
Brief Title
Effect of Vasopressin, Steroid, and Epinephrine Treatment in Patients With Out-of-hospital Cardiac Arrest
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Unknown status
Study Start Date
January 1, 2018 (Anticipated)
Primary Completion Date
August 9, 2020 (Anticipated)
Study Completion Date
August 9, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Korea University Guro Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Arrest
Keywords
Out-of-Hospital Cardiac Arrest, Vasopressin-steroid-epinephrine (VSE), Treatment Outcome, prognosis, Return of spontaneous circulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Factorial Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
834 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control Group
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
Experimental Group 1
Arm Type
Active Comparator
Arm Description
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
Arm Title
Experimental Group 2
Arm Type
Active Comparator
Arm Description
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
Arm Title
Experimental Group 3
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Control Group
Other Intervention Name(s)
Epinephrine
Intervention Description
Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) only
Intervention Type
Drug
Intervention Name(s)
Experimental Group 1
Other Intervention Name(s)
Epinephrine + Vasopressin
Intervention Description
Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) and Vasopressin(20 international unit(IU)/cardiopulmonary resuscitation(CPR) cycle)
Intervention Type
Drug
Intervention Name(s)
Experimental Group 2
Other Intervention Name(s)
Epinephrine + Steroid
Intervention Description
Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) and Steroid(Methylprednisolone, 40 mg at first cycle)
Intervention Type
Drug
Intervention Name(s)
Experimental Group 3
Other Intervention Name(s)
Epinephrine + Vasopressin + Steroid
Intervention Description
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)
Primary Outcome Measure Information:
Title
Examined for neurological prognosis of each group
Description
- main result variables: survival discharge with good CPC (CPC 1 or 2)
Time Frame
survival discharge, through study completion, an average of 1 year
Secondary Outcome Measure Information:
Title
Examined for return of spontaneous circulation (ROSC) status
Description
sustained ROSC (more than 20mins)
Time Frame
ROSC, up to 24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jung-Youn Kim, MD, Ph.D.
Phone
82-2-2626-3285
Email
yellowwizard@hanmail.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jung-Youn Kim, MD, Ph.D.
Organizational Affiliation
Assistant Professor
Official's Role
Principal Investigator
Facility Information:
Facility Name
Korea University Guro Hospital
City
Seoul
State/Province
Guro-gu
ZIP/Postal Code
08308
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Seung-hoe Song, MBE
Phone
82-2-2626-1635
Email
ssessong@korea.ac.kr

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
19139319
Citation
Mentzelopoulos SD, Zakynthinos SG, Tzoufi M, Katsios N, Papastylianou A, Gkisioti S, Stathopoulos A, Kollintza A, Stamataki E, Roussos C. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest. Arch Intern Med. 2009 Jan 12;169(1):15-24. doi: 10.1001/archinternmed.2008.509.
Results Reference
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PubMed Identifier
16321716
Citation
Nolan JP, Deakin CD, Soar J, Bottiger BW, Smith G; European Resuscitation Council. European Resuscitation Council guidelines for resuscitation 2005. Section 4. Adult advanced life support. Resuscitation. 2005 Dec;67 Suppl 1:S39-86. doi: 10.1016/j.resuscitation.2005.10.009. No abstract available.
Results Reference
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PubMed Identifier
23860985
Citation
Mentzelopoulos SD, Malachias S, Chamos C, Konstantopoulos D, Ntaidou T, Papastylianou A, Kolliantzaki I, Theodoridi M, Ischaki H, Makris D, Zakynthinos E, Zintzaras E, Sourlas S, Aloizos S, Zakynthinos SG. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013 Jul 17;310(3):270-9. doi: 10.1001/jama.2013.7832.
Results Reference
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PubMed Identifier
27436285
Citation
Mentzelopoulos SD, Mongardon N, Xanthos T, Zakynthinos SG. Possible significance of hemodynamic and immunomodulatory effects of early stress-dose steroids in cardiac arrest. Crit Care. 2016 Jul 20;20(1):211. doi: 10.1186/s13054-016-1384-4. No abstract available.
Results Reference
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PubMed Identifier
27038920
Citation
Donnino MW, Andersen LW, Berg KM, Chase M, Sherwin R, Smithline H, Carney E, Ngo L, Patel PV, Liu X, Cutlip D, Zimetbaum P, Cocchi MN; Collaborating Authors from the Beth Israel Deaconess Medical Center's Center for Resuscitation Science Research Group. Corticosteroid therapy in refractory shock following cardiac arrest: a randomized, double-blind, placebo-controlled, trial. Crit Care. 2016 Apr 3;20:82. doi: 10.1186/s13054-016-1257-x.
Results Reference
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PubMed Identifier
26472995
Citation
Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, Neumar RW, O'Neil BJ, Paxton JH, Silvers SM, White RD, Yannopoulos D, Donnino MW. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015 Nov 3;132(18 Suppl 2):S444-64. doi: 10.1161/CIR.0000000000000261. No abstract available. Erratum In: Circulation. 2015 Dec 15;132(24):e385.
Results Reference
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PubMed Identifier
16984836
Citation
Kim JJ, Lim YS, Shin JH, Yang HJ, Kim JK, Hyun SY, Rhoo I, Hwang SY, Lee G. Relative adrenal insufficiency after cardiac arrest: impact on postresuscitation disease outcome. Am J Emerg Med. 2006 Oct;24(6):684-8. doi: 10.1016/j.ajem.2006.02.017.
Results Reference
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Citation
Kim JY, Shin SD, Ro YS, Song KJ, Lee EJ, Park CB, Hwang SS; CardioVascular Disease Surveillance (CAVAS) investigators. Post-resuscitation care and outcomes of out-of-hospital cardiac arrest: a nationwide propensity score-matching analysis. Resuscitation. 2013 Aug;84(8):1068-77. doi: 10.1016/j.resuscitation.2013.02.010. Epub 2013 Feb 27.
Results Reference
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Effect of Vasopressin, Steroid, and Epinephrine Treatment in Patients With Out-of-hospital Cardiac Arrest

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