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Arterial Pressure and Stress-Dose Steroids in Cardiac Arrest.

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ClinicalTrials.gov Identifier: NCT02785224
Recruitment Status : Not yet recruiting
First Posted : May 27, 2016
Last Update Posted : August 17, 2017
Sponsor:
Collaborator:
University of Thessaly
Information provided by (Responsible Party):
Spyros D. Mentzelopoulos, University of Athens

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).

Condition or disease Intervention/treatment
Cardiac Arrest Drug: Vasopressin Steroids Epinephrine

  Show Detailed Description

Study Type : Observational
Estimated Enrollment : 191 participants
Observational Model: Other
Time Perspective: Retrospective
Official Title: Arterial Pressure and Stress-Dose Steroids in In-hospital Cardiac Arrest: a Mediation Analysis of Prior Randomized Clinical Trial Data.
Estimated Study Start Date : May 2018
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018


Group/Cohort Intervention/treatment
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
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.
Other Name: VSE

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.



Primary Outcome Measures :
  1. Early postresuscitation systolic arterial pressure (SAP) as mediator of observed intervention benefit. [ Time Frame: 20 min after return of spontaneous circulation (ROSC) ]
    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.

  2. Early postresuscitation mean arterial pressure (MAP) as mediator of observed intervention benefit [ Time Frame: 24 hours after ROSC ]
    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.


Secondary Outcome Measures :
  1. Renal failure free days and SAP [ Time Frame: Days 1-60 after ROSC ]
    Addition of renal failure free days to the primary mediation analysis "SAP" model - this will result in a first "multiple mediator" SAP model.

  2. Renal failure free days and MAP [ Time Frame: Days 1-60 after ROSC ]
    Addition of renal failure free days to the primary mediation analysis "MAP" model - this will result in a first "multiple mediator" MAP model.

  3. Arterial blood lactate level > 4.65 mmol/L at 4 hours post-ROSC and SAP [ Time Frame: 4 hours post-ROSC ]
    Addition of arterial blood lactate at 4 hours post-ROSC > 4.65 mmol/L (median value in 191 patients) to the first "multiple mediator" SAP model - this will result in the second "multiple mediator" SAP model.

  4. Arterial blood lactate level > 4.65 mmol/L at 4 hours post-ROSC and MAP [ Time Frame: 4 hours post-ROSC ]
    Addition of arterial blood lactate at 4 hours post-ROSC > 4.65 mmol/L (median value in 191 patients) to the first "multiple mediator" MAP model - this will result in the second "multiple mediator" MAP model.

  5. Arterial blood lactate level > 2.80 mmol/L at 4 hours post-ROSC and SAP [ Time Frame: 4 hours post-ROSC ]
    Addition of arterial blood lactate at 4 hours post-ROSC > 2.80 mmol/L (lower bound of interquartile range in 191 patients) to the first "multiple mediator" SAP model - this will result in the third "multiple mediator" SAP model.

  6. Arterial blood lactate level > 2.80 mmol/L at 4 hours post-ROSC and MAP [ Time Frame: 4 hours post-ROSC ]
    Addition of arterial blood lactate at 4 hours post-ROSC > 2.80 mmol/L (lower bound of interquartile range in 191 patients) to the first "multiple mediator" MAP model - this will result in the third "multiple mediator" MAP model.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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;
  • Previous enrollment in or exclusion from the 2 studies included in the analysis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02785224


Contacts
Contact: Spyros D Mentzelopoulos, MD, PhD +306975304909 sdmentzelopoulos@yahoo.com
Contact: Spyros G Zakynthinos, MD, PhD +306977673885 szakynthinos@yahoo.com

Locations
Greece
Evaggelismos General Hospital Not yet recruiting
Athens, Attica, Greece, 10676
Contact: Spyros D Mentzelopoulos, MD, PhD    +306975304909    sdmentzelopoulos@yahoo.com   
Contact: Spyros G Zakynthinos, MD, PhD    +306977673885    szakynthinos@yahoo.com   
401 General Military Hospital of Athens Not yet recruiting
Athens, Attica, Greece, GR-11526
Contact: Sotiris Sourlas, MD    +306945384117    stavrinavg@yahoo.gr   
Principal Investigator: Sotiris Sourlas, MD         
Sub-Investigator: Aloizos Stavros, MD         
Larisa University General Hospital
Larisa, Thessaly, Greece, GR-41110
Sponsors and Collaborators
University of Athens
University of Thessaly
Investigators
Principal Investigator: Spyros D. Mentzelopoulos, MD, PhD University of Athens
Study Chair: Spyros G. Zakynthinos, MD, PhD University of Athens

Publications of Results:
Other Publications:
Responsible Party: Spyros D. Mentzelopoulos, MD, PhD, DEAA, EDIC, Associate Professor of Intensive Care Medicine, University of Athens
ClinicalTrials.gov Identifier: NCT02785224     History of Changes
Other Study ID Numbers: AP-MEDIATION-15516/23/5/16
First Posted: May 27, 2016    Key Record Dates
Last Update Posted: August 17, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Heart Arrest
Heart Diseases
Cardiovascular Diseases
Epinephrine
Racepinephrine
Epinephryl borate
Vasopressins
Arginine Vasopressin
Methylprednisolone
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-Agonists
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Mydriatics
Sympathomimetics
Vasoconstrictor Agents
Anti-Inflammatory Agents
Antiemetics
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists