Vasopressin, Epinephrine, and Steroids for Cardiac Arrest

NCT00729794 | Completed Phase 3 DMC

• 1 other identifier: VSE-226-2008
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 3

Brief Summary

The simultaneous activation of adrenergic and vasopressin receptors, in conjunction with a potential steroid-mediated enhancement of the vascular reactivity to epinephrine may have beneficial effects in patients with cardiac arrest. This hypothesis is supported by the single-center results of NCT 00411879. The investigators intend to either refute or provide definitive evidence supporting this hypothesis (and its generalizability) by conducting the present multicenter, randomized, controlled clinical trial of in hospital cardiac arrest.

Conditions

Cardiac Arrest

Keywords

Vasopressin; Epinephrine; Adrenal Cortex Hormones; Heart Arrest

Outcome Measures

Primary Outcomes (1)

• Return of Spontaneous Circulation for at least 15 min and Survival to Hospital Discharge with or without neurological recovery

  60 days

Secondary Outcomes (3)

• Arterial pressure and gas exchange during CPR and at 15-20 min following return of spontaneous circulation; hemodynamic status during days 1 to 10 post-randomization

  30 min to 10 days

• The number of organ failure-free days during follow-up

  60 days

• Complications related to the use of steroids

  10 days

Study Arms (2)

Study Group

EXPERIMENTAL

Patients with refractory, inhospital cardiac arrest, i.e., with asystole, pulseless electrical activity, or ventricular fibrillation/pulseless ventricular tachycardia not responsive to two attempts at defibrillation.

Drug: Vasopressin, Epinephrine, Methylprednisolone, Hydrocortisone

Control Group

PLACEBO COMPARATOR

Patients with refractory, inhospital cardiac arrest, i.e., with asystole, pulseless electrical activity, or ventricular fibrillation/pulseless ventricular tachycardia not responsive to two attempts at defibrillation.

Drug: Standard CPR Protocol with Epinephrine and two Placebos

Interventions

Vasopressin, Epinephrine, Methylprednisolone, Hydrocortisone DRUG

Combination Treatment Administration of vasopressin, epinephrine, and methylprednisolone during CPR, and of stress dose hydrocortisone after CPR

Study Group

Standard CPR Protocol with Epinephrine and two Placebos DRUG

Patients receive advanced life support according to the Guidelines for Resuscitation 2005

Control Group

Eligibility Criteria

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

You may qualify if:

• Adult patients with refractory inhospital cardiac arrest, defined as epinephrine requirement for ventricular fibrillation/tachycardia or asystole/pulseless electrical activity according to guidelines for resuscitation 2005 (5).

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, GR-10675, Greece

Location

401 General Military Hospital of Athens

Athens, Attica, GR-11526, Greece

Location

University General Hospital of Larissa

Larissa, Thessaly, GR-41110, Greece

Location

Related Publications (9)

• Sandroni C, Nolan J, Cavallaro F, Antonelli M. In-hospital cardiac arrest: incidence, prognosis and possible measures to improve survival. Intensive Care Med. 2007 Feb;33(2):237-45. doi: 10.1007/s00134-006-0326-z. Epub 2006 Sep 22.

  PMID: 17019558 BACKGROUND

• Stiell IG, Hebert PC, Wells GA, Vandemheen KL, Tang AS, Higginson LA, Dreyer JF, Clement C, Battram E, Watpool I, Mason S, Klassen T, Weitzman BN. Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial. Lancet. 2001 Jul 14;358(9276):105-9. doi: 10.1016/S0140-6736(01)05328-4.

  PMID: 11463411 BACKGROUND

• Adrie C, Laurent I, Monchi M, Cariou A, Dhainaou JF, Spaulding C. Postresuscitation disease after cardiac arrest: a sepsis-like syndrome? Curr Opin Crit Care. 2004 Jun;10(3):208-12. doi: 10.1097/01.ccx.0000126090.06275.fe.

  PMID: 15166838 BACKGROUND

• Hekimian G, Baugnon T, Thuong M, Monchi M, Dabbane H, Jaby D, Rhaoui A, Laurent I, Moret G, Fraisse F, Adrie C. Cortisol levels and adrenal reserve after successful cardiac arrest resuscitation. Shock. 2004 Aug;22(2):116-9. doi: 10.1097/01.shk.0000132489.79498.c7.

  PMID: 15257083 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

• Shizukuda Y, Miura T, Ishimoto R, Itoya M, Iimura O. Effect of prednisolone on myocardial infarct healing: characteristics and comparison with indomethacin. Can J Cardiol. 1991 Dec;7(10):447-54.

  PMID: 1768984 BACKGROUND

• A randomized clinical trial of calcium entry blocker administration to comatose survivors of cardiac arrest. Design, methods, and patient characteristics. The Brain Resuscitation Clinical Trial II Study Group. Control Clin Trials. 1991 Aug;12(4):525-45. doi: 10.1016/0197-2456(91)90011-a.

  PMID: 1657528 BACKGROUND

• Holmberg MJ, Granfeldt A, Mentzelopoulos SD, Andersen LW. Vasopressin and glucocorticoids for in-hospital cardiac arrest: A systematic review and meta-analysis of individual participant data. Resuscitation. 2022 Feb;171:48-56. doi: 10.1016/j.resuscitation.2021.12.030. Epub 2022 Jan 3.

  PMID: 34990764 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Heart Arrest; Diabetes Insipidus

Interventions

Vasopressins; Epinephrine; Methylprednisolone; Hydrocortisone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; 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; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids

Study Officials

• Spyros D Mentzelopoulos, MD, PhD

  University of Athens Medical School, Athens, Greece

  PRINCIPAL INVESTIGATOR

• Spyros G Zakynthinos, MD, PhD

  University of Athens Medical School, Athens, Greece

  STUDY DIRECTOR

• Charis Roussos, MD, PhD

  University of Athens Medical School, Athens, Greece

  STUDY CHAIR

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: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor in Intensive Care Medicine

Study Record Dates

• First Submitted: July 31, 2008
• First Posted: August 8, 2008
• Study Start: September 1, 2008
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: November 21, 2016

Record last verified: 2016-11

Locations

GR (3)