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

A Randomized Clinical Trial of Patient Outcomes Following Out-of-Hospital Cardiac Arrest Receiving Epinephrine Versus In-together Vasopressin, Epinephrine, and Steroid. (OHCA REVIVES Trial)

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).

Study Overview

• Status: Recruiting
• Conditions: Cardiac Arrest; Emergency Medical Services; Out-Of-Hospital Cardiac Arrest
• Intervention / Treatment: Drug: Combination group; Drug: Standard group

Detailed Description

The global and Taiwanese survival rates for patients following an out-of-hospital cardiac arrest (OHCA) are less than 10%. The emergency medical system (EMS) plays a crucial role in patient outcomes after OHCA, providing prehospital cardiopulmonary resuscitation, defibrillation, and medication. Among these medications, the combination of epinephrine, vasopressin, and methylprednisolone holds the most potential to improve patient survival rates following OHCA.

This study aims to compare the effect of standard epinephrine therapy with a combination of epinephrine, vasopressin, and methylprednisolone administered to OHCA patients. This comparison will be made through a randomized clinical trial (RCT) within the EMS of Taipei City and New Taipei City.

Throughout the research plan, we will conduct a prehospital RCT to answer the following question (in P-I-C-O format): Will adult non-traumatic OHCA patients resuscitated by paramedics in a prehospital setting have a better chance of sustained recovery of spontaneous circulation (primary outcome), and improved survival status (secondary outcomes), if they receive combination therapy (i.e., standard doses of epinephrine, 20U of vasopressin after each dose of epinephrine up to a maximum of 80U, and one dose of 40mg methylprednisolone after the first dose of epinephrine) compared to those who receive standard doses of epinephrine? We estimate a sample size of 1,344 OHCA patients to detect a difference in the primary outcome. Based on the background data from the EMS regions under study, we expect the enrollment to take approximately 30 months to complete.

This study is referred to as the "OHCA-REVIVES" trial, which stands for A randomized clinical trial of patient outcomes following Out-of-Hospital Cardiac Arrest Receiving Epinephrine Versus In-together Vasopressin, Epinephrine, and Steroid. The anticipated results from the "OHCA-REVIVES trial" will help determine the optimal strategy for prehospital medication, and will undoubtedly have a significant impact on resuscitation science. Through these efforts, we aim to improve the outcomes of OHCA patients.

• Study Type: Interventional
• Enrollment (Estimated): 1344
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: WEN CHU CHIANG, PhD; Phone Number: +886 926131851; Email: drchiang.tw@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Wen-Chu Chiang, MD, PhD; Phone Number: 886-2-23123456; Email: drchiang.tw@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients (aged >= 18 )
• Out-of-hospital cardiac arrest in the studied regions
• Treated by paramedics authorized and capable of giving prehospital medication

Exclusion Criteria:

• OHCA with traumatic etiology
• Obvious signs of death like decapitation, rigor mortis, livor mortis, decomposition, etc.
• DNR (Do Not Resuscitation) or termination of resuscitation requested by the family
• Patients with known or suspected pregnancy
• No vascular access was established before hospital arrival
• ROSC before the administrated medication
• No patient contact (cancelled ambulance call or the patient was transported to the hospital before the arrival of trial-trained paramedics)
• Received epinephrine prior to the arrival of trial-trained paramedics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; Combined drug treatment: includes epinephrine (Adrenaline® 1mg/vial) every 3-5 minutes, vasopressin (Pitressin® 20Unints/vial) every 3-5 minutes up to 4 vials (a total of 80Units), methylprednisolone (Solu-Medrol® 40mg/vial). The method of administration is as follows: after the first administration of epinephrine (Adrenaline® 1mg/vial) to patients with cardiac arrest before hospital arrival, vasopressin (Pitressin® 20Unints/vial) and methylprednisolone (Solu-Medrol® 40mg/vial) are given simultaneously; thereafter, every 3-5 minutes, 1 mg (1 dose) of (Adrenaline® 1mg/vial) is given, along with 20 Units (1 dose) of vasopressin (Pitressin® 20Unints/vial) up to a maximum of 4 doses (a total of 80 Units) of vasopressin can be given before hospital arrival.	Drug: Combination group; Combination of epinephrine (Adrenaline® 1mg/vial) every 3-5 minutes, vasopressin (Pitressin® 20Unints/vial) every 3-5 minutes up to 4 vials (a total of 80Units), methylprednisolone (Solu-Medrol® 40mg/vial)
Active Comparator: Control group; Standard drug treatment: epinephrine (Adrenaline® 1mg/vial). According to international resuscitation guidelines ( Advanced Cardiac Life Support, ACLS), patients with cardiac arrest before hospital arrival are given 1 mg (1 dose) of epinephrine (Adrenaline® 1mg/vial) every 3-5 minutes.	Drug: Standard group; standard doses of epinephrine (Adrenaline® 1mg/vial) every 3-5 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of sustained return of spontaneous circulation (ROSC)	Return of spontaneous circulation (ROSC) is the restart of a sustained heart rhythm measured by pulsation and vital signs that permeate the body after a cardiac arrest. Sustained ROSC ≥ 2 hours has been used as an surrogate to survival to hospital admission in many overcrowded emergency departments (ED).	estimated 2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of prehospital return of spontaneous circulation (ROSC)	presence of ROSC prior to arrival at emergency department (ED)	estimated 1 hour
Rate of survival to hospital discharge	survival to hospital admission, and without in-hospital death	estimated 30 days
Rate of survival with favorable neurologic status	Good neurologic status (defined as Cerebral-Performance Category (CPC) score 1 and 2) at hospital discharge	estimated 30 days

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: WEN CHU CHIANG, Phd, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 18, 2023
• First Submitted That Met QC Criteria: January 2, 2024
• First Posted (Actual): January 12, 2024

Study Record Updates

• Last Update Posted (Actual): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 16, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Emergency Medical Services; Corticosteroid; Vasopressin; Epinephrine; Out-Of-Hospital Cardiac Arrest
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Cardiovascular Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Pituitary Diseases; Heart Arrest; Out-of-Hospital Cardiac Arrest; Diabetes Insipidus
• Other Study ID Numbers: 202204115MINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon completion of the study, the sharing of Individual Participant Data (IPD) will be made available in accordance with local privacy protection laws.
• IPD Sharing Time Frame: Upon completion of the study, estimated at the end of 2026, the sharing of Individual Participant Data (IPD) will be made available following local privacy protection laws.
• IPD Sharing Access Criteria: reasonable request to the corresponding authors.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No