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

NCT ID: NCT03317197

Last Updated: 2017-10-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 834 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-01
• Study Completion Date: 2020-08-09

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.

Conditions

Cardiac Arrest

Keywords

Out-of-Hospital Cardiac Arrest; Vasopressin-steroid-epinephrine (VSE); Treatment Outcome; prognosis; Return of spontaneous circulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Control Group

• 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

Group Type: PLACEBO_COMPARATOR

Control Group

Intervention Type: DRUG

Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) only

Experimental Group 1

• 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

Group Type: ACTIVE_COMPARATOR

Experimental Group 1

Intervention Type: DRUG

Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) and Vasopressin(20 international unit(IU)/cardiopulmonary resuscitation(CPR) cycle)

Experimental Group 2

• 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

Group Type: ACTIVE_COMPARATOR

Experimental Group 2

Intervention Type: DRUG

Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) and Steroid(Methylprednisolone, 40 mg at first cycle)

Experimental Group 3

• 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

Group Type: EXPERIMENTAL

Experimental Group 3

Intervention Type: DRUG

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)

Interventions

Control Group

Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) only

Intervention Type: DRUG

Experimental Group 1

Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) and Vasopressin(20 international unit(IU)/cardiopulmonary resuscitation(CPR) cycle)

Intervention Type: DRUG

Experimental Group 2

Using Epinephrine(1 mg/cardiopulmonary resuscitation(CPR) cycle) and Steroid(Methylprednisolone, 40 mg at first cycle)

Intervention Type: DRUG

Experimental Group 3

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)

Intervention Type: DRUG

Other Intervention Names

Epinephrine; Epinephrine + Vasopressin; Epinephrine + Steroid; Epinephrine + Vasopressin + Steroid

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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Korea University Guro Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jung-Youn Kim

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jung-Youn Kim, MD, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Assistant Professor

Locations

Korea University Guro Hospital

Seoul, Guro-gu, South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Jung-Youn Kim, MD, Ph.D.

Role: CONTACT

Phone: 82-2-2626-3285

Email: yellowwizard@hanmail.net

Facility Contacts

Seung-hoe Song, MBE

Role: primary

References

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Reference Type: BACKGROUND

PMID: 19139319 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16321716 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23860985 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27436285 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27038920 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26472995 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16984836 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23454438 (View on PubMed)

Other Identifiers

KUGH17156 (VSE study)

Identifier Type: -

Identifier Source: org_study_id