VAsopressin and STeroids in Addition to Adrenaline in Cardiac Arrest - a Randomized Clinical Trial (VAST-A)

This is an investigator initiated randomized, placebo controlled, double blind, superiority, multi-centre clinical trial. The estimated study project period runs over 3-4 years, including pilot phase. Based on preliminary assumptions, to confirm or reject an increase in survival from 9% to 14%, about1400 patients will be randomized in the study. In hospital cardiac arrest patients meeting criteria(s) for adrenaline administration according to current ERC guidelines are eligible for randomization in the study.

Informed consent for participating in the study cannot be obtained from the subject at the scene of the cardiac arrest since the victim is unconscious. Therefore, all hospitalized men > 18 years and women > 50 years, except those fulfilling the exclusion criterias; patients not capable to comprehend information to decide about participation in the study, women considered of childbearing potential (WOCBP)) and do not resuscitate (DNR) decision will be informed and asked about consent to participate in the study and in the case of cardiac arrest during the actual hospital stay randomized to either treatment. Only those patients experiencing an in hospital cardiac arrest meeting criteria(s) for adrenaline administration will be randomized.

Patients will be randomized to, in addition adrenaline, either treatment with vasopressin and steroids (intervention) or sodium chloride (placebo) (control).

Primary outcome is survival at 30 days.

Study Overview

• Status: Recruiting
• Conditions: Cardiac Arrest;In-hospital Cardiac Arrest; Methylprednisolone; Vasopressin; Adrenaline; Randomized Clinical Trial
• Intervention / Treatment: Drug: Vasopressin; Methylprednisolone; Hydrocortisone; Drug: Sodium chloride

• Study Type: Interventional
• Enrollment (Anticipated): 1276
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sune Forsberg, MD, PhD; Phone Number: +46722037953; Email: sune.forsberg@tiohundra.se

Study Locations

• Sweden
  • Gothenburg, Sweden
    • Recruiting
    • Sahlgrenska University Hospital
    • Contact: Peter Lundgren, MD, PhD; Phone Number: +46706678316; Email: peter.lundgren@vgregion.se
  • Norrtälje, Sweden
    • Recruiting
    • Tiohundra
    • Contact: Sune Forsberg; Phone Number: +46722037953; Email: sune.forsberg@tiohundra.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hospitalized men > 18 years and hospitalized women > 50 years.

Exclusion Criteria:

• Patients not capable to comprehend information to decide about participation in the study
• Women considered of childbearing potential (WOCBP) i. e. premenopausal women
• Patients with do not resuscitate (DNR) descision
• Prior enrollment and randomization in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention; Adrenaline, vasopressin and steroids arm (intervention); At randomization1 ml of vasopressin 20 IU/ml will be administered as soon as possible after adrenaline during the five first cycles of drug administration during CPR.1 ml metylprednisolone sodium succinate 40 mg/ml will be administered only during the first cycle of drug administration during CPR; In the ICU Hydrocortisone 3 mg/ml At 4 hours post ROSC, and then once daily, surviving patients with post-resuscitation shock will receive an infusion of 100 ml (300 mg hydrocortisone/ d) for ≤ 7 days. From day 8 post ROSC or when vasopressors are not needed the hydrocortisone dos will be reduced daily to 67 ml (200 mg) and 33 ml (100 mg) and then discontinued). Patients with evidence of acute myocardial infarction will receive an infusion of 100 ml (300mg hydrocortisone/ d) for maximum 3 days to prevent retardation of infarct healing.	Drug: Vasopressin; Methylprednisolone; Hydrocortisone; Vasopressin, the vasoconstrictive hypophysal hormone, alone has not shown increased survival when compared to adrenaline. However, animal data have shown increased diastolic pressure, cerebral perfusion pressure and cerebral oxygenation in cardiac arrest treatment with vasopressin, and have when compared to adrenaline been associated with better cerebral blood flow. Corticosteroids are currently used in septic shock treatment as a means to reduce time to shock reversal and thereby potentially improving mortality. Steroids have therefore also been suggested for cardiac arrest treatment. The potential role in resuscitation includes the catecholaminerg potentiation, vasoconstriction and protection from reperfusion injury.
Placebo Comparator: Control; Adrenaline alone arm (control); At randomization 1 ml sodium chloride 9 mg/ml (placebo) will be administered as soon as possible after adrenaline during the first five cycle of drug administration during CPR 1 ml sodium chloride 9 mg/ml (placebo) will be administered only during the first cycle of drug administration during CPR b In the ICU sodium chloride 9 mg/ml (placebo) At 4 hours post ROSC, and then once daily, surviving patients with post-resuscitation shock will receive an infusion of 100 ml for ≤ 7 days. From day 8 post ROSC or when vasopressors are not needed the dos will be reduced daily to 67 ml and 33 ml and then discontinued. Patients with evidence of acute myocardial infarction will receive an infusion of 100 ml for 3 days.	Drug: Sodium chloride; Sodium chloride 9 mg/ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival at 30 days	Survival at 30 days	Survival at 30 days

Collaborators and Investigators

• Sponsor: Tiohundra AB
• Collaborators: Sahlgrenska University Hospital, Sweden; Stockholm South General Hospital
• Investigators: Principal Investigator: Sune Forsberg, MD, PhD, Tiohundra AB; Principal Investigator: Peter Lundgren, MD, PhD, Sahlgrenska University Hospital, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2021
• Primary Completion (Anticipated): January 31, 2027
• Study Completion (Anticipated): April 30, 2027

Study Registration Dates

• First Submitted: November 17, 2021
• First Submitted That Met QC Criteria: November 30, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Actual): January 20, 2022
• Last Update Submitted That Met QC Criteria: January 19, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Natriuretic Agents; Hemostatics; Coagulants; Vasoconstrictor Agents; Antidiuretic Agents; Methylprednisolone; Hydrocortisone; Vasopressins; Arginine Vasopressin
• Other Study ID Numbers: VAST-A.Studyprotocol.Version_4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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