VAsopressin and STeroids in Addition to Adrenaline in Cardiac Arrest - a Randomized Clinical Trial

NCT05139849 | Recruiting Phase 3

• 1 other identifier: VAST-A.Studyprotocol.Version_4
• Study Type: interventional
• Target: 1,276
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Cardiac Arrest;In-hospital Cardiac Arrest; Methylprednisolone; Vasopressin; Adrenaline; Randomized Clinical Trial

Outcome Measures

Primary Outcomes (1)

• Survival at 30 days

  Survival at 30 days

  Survival at 30 days

Study Arms (2)

Intervention

ACTIVE COMPARATOR

Adrenaline, vasopressin and steroids arm (intervention) 1. At randomization 1 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 2. 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

Control

PLACEBO COMPARATOR

Adrenaline alone arm (control) 1. 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

Interventions

Vasopressin; Methylprednisolone; Hydrocortisone DRUG

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.

Intervention

Sodium chloride DRUG

Sodium chloride 9 mg/ml

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tiohundra AB: lead
• Sahlgrenska University Hospital: collaborator
• Stockholm South General Hospital: collaborator

Study Sites (2)

Sahlgrenska University Hospital

Gothenburg, Sweden

RECRUITING

Tiohundra

Norrtälje, Sweden

RECRUITING

Related Publications (1)

• Andersen LW, Holmberg MJ, Hoybye M, Isbye D, Kjaergaard J, Darling S, Zwisler ST, Larsen JM, Rasmussen BS, Iversen K, Schultz M, Sindberg B, Fink Valentin M, Granfeldt A. Vasopressin and methylprednisolone and hemodynamics after in-hospital cardiac arrest - A post hoc analysis of the VAM-IHCA trial. Resuscitation. 2023 Oct;191:109922. doi: 10.1016/j.resuscitation.2023.109922. Epub 2023 Aug 3.

  PMID: 37543161 DERIVED

MeSH Terms

Conditions

Diabetes Insipidus

Interventions

Vasopressins; Methylprednisolone; Hydrocortisone; Sodium Chloride

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Sune Forsberg, MD, PhD

  Tiohundra AB

  PRINCIPAL INVESTIGATOR

• Peter Lundgren, MD, PhD

  Sahlgrenska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sune Forsberg, MD, PhD

CONTACT

+46722037953; sune.forsberg@tiohundra.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2021
• First Posted: December 1, 2021
• Study Start: November 17, 2021
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: January 20, 2022

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)