Arterial Pressure and Stress-Dose Steroids in Cardiac Arrest.

NCT02785224 | Withdrawn

• 1 other identifier: AP-MEDIATION-15516/23/5/16
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

Early stress-dose steroids are of uncertain efficacy in cardiac arrest. The current authors plan to conduct a pertinent mediation analysis using prospectively collected data from 2 prior randomized clinical trials of in-hospital cardiac arrest. These trials reported positive results on the vasopressin-steroids-epinephrine (VSE) combination. The current analysis is aimed at identifying mediators of the benefit associated with VSE, potentially attributable to its stress-dose steroid subcomponent. Tested mediators will include arterial pressure in the early postresuscitation period (primary), and arterial blood lactate in the early postresuscitation period and renal failure free days (secondary).

Conditions

Cardiac Arrest

Outcome Measures

Primary Outcomes (2)

• Early postresuscitation systolic arterial pressure (SAP) as mediator of observed intervention benefit.

  Determination of the possible mediating role of SAP with respect to the observed vasopressin-steroids-epinephrine (VSE) outcome benefit. Multivariable mediation analysis of the following possible relationship: VSE intervention - postresuscitation SAP\>90 mmHg at 20 min post-ROSC - Survival with good neurological recovery i.e. Cerebral Performance Category (CPC) score of 1 or 2.This will result in the primary mediation analysis "SAP" model.

  20 min after return of spontaneous circulation (ROSC)

• Early postresuscitation mean arterial pressure (MAP) as mediator of observed intervention benefit

  Determination of the possible mediating role of MAP with respect to the observed VSE outcome benefit. Multivariable mediation analysis of the following possible relationship: VSE intervention - at least 1 day-1 postrandomization MAP value\>80 mmHg - Survival with good neurological recovery i.e. CPC score of 1 or 2. This will result in the primary mediation analysis "MAP" model.

  24 hours after ROSC

Secondary Outcomes (6)

• Renal failure free days and SAP

  Days 1-60 after ROSC

• Renal failure free days and MAP

  Days 1-60 after ROSC

• Arterial blood lactate level > 4.65 mmol/L at 4 hours post-ROSC and SAP

  4 hours post-ROSC

• Arterial blood lactate level > 4.65 mmol/L at 4 hours post-ROSC and MAP

  4 hours post-ROSC

• Arterial blood lactate level > 2.80 mmol/L at 4 hours post-ROSC and SAP

  4 hours post-ROSC

Study Arms (2)

Vasopressin Steroids Epinephrine (VSE)

Patients with in-hospital cardiac arrest treated with vasopressin, methylprednisolone, and epinephrine during cardiopulmonary resuscitation, and also with stress-dose hydrocortisone for postresuscitation shock.

Drug: Vasopressin Steroids Epinephrine

Control

Patients with in-hospital cardiac arrest treated with normal saline placebo, normal saline placebo, and epinephrine during cardiopulmonary resuscitation, and also with normal saline placebo for postresuscitation shock.

Interventions

Vasopressin Steroids Epinephrine DRUG

Vasopressin Steroids Epinephrine: Vasopressin (up to 5 doses of 20 IU) and methylprednisolone (single dose - 40 mg) in addition to epinephrine during cardiopulmonary resuscitation, and stress dose hydrocortisone (300 mg/day for 7 days maximum followed by gradual taper) for postresuscitation shock.

Also known as: VSE

Vasopressin Steroids Epinephrine (VSE)

Eligibility Criteria

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

Study Population

Adult patients with vasopressor-requiring, inhospital cardiac arrest, i.e., with asystole, pulseless electrical activity, or ventricular fibrillation/pulseless ventricular tachycardia not responsive to two attempts at defibrillation. Patients have already participated in 2 prior RCTs (references 3 and 4). Thus, the below-provided Eligibility Criteria are the Criteria already employed by the prior RCTs.

You may qualify if:

• Adult patients with vasopressor-requiring inhospital cardiac arrest according to guidelines for resuscitation 2005, defined as:
• epinephrine requirement for ventricular fibrillation/tachycardia
• or asystole, or
• pulseless electrical activity

You may not qualify if:

• Age \< 18 years;
• Terminal illness or do-not resuscitate status;
• Cardiac arrest due to exsanguination;
• Cardiac arrest before hospital admission;
• Pre-arrest treatment with intravenous corticosteroids;

Sponsors & Collaborators

• University of Athens: lead
• University of Thessaly: collaborator

Study Sites (3)

Evaggelismos General Hospital

Athens, Attica, 10676, Greece

Location

401 General Military Hospital of Athens

Athens, Attica, GR-11526, Greece

Location

Larisa University General Hospital

Larissa, Thessaly, GR-41110, Greece

Location

Related Publications (6)

• 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.

  PMID: 27038920 BACKGROUND

• Trzeciak S, Jones AE, Kilgannon JH, Milcarek B, Hunter K, Shapiro NI, Hollenberg SM, Dellinger P, Parrillo JE. Significance of arterial hypotension after resuscitation from cardiac arrest. Crit Care Med. 2009 Nov;37(11):2895-903; quiz 2904. doi: 10.1097/ccm.0b013e3181b01d8c.

  PMID: 19866506 BACKGROUND

• 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.

  PMID: 19139319 BACKGROUND

• 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.

  PMID: 23860985 BACKGROUND

• 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.

  PMID: 26472995 BACKGROUND

• 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.

  PMID: 16321716 BACKGROUND

MeSH Terms

Conditions

Heart Arrest

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Spyros D. Mentzelopoulos, MD, PhD

  University of Athens

  PRINCIPAL INVESTIGATOR

• Spyros G. Zakynthinos, MD, PhD

  University of Athens

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, DEAA, EDIC, Associate Professor of Intensive Care Medicine

Study Record Dates

• First Submitted: May 22, 2016
• First Posted: May 27, 2016
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GR (3)