Physiologic Effects of Steroids in Cardiac Arrest

NCT02790788 | Completed Phase 1 Results DMC

• 1 other identifier: CORTICA-15519/23/5/16
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

Early stress-dose steroids are of uncertain efficacy in cardiac arrest. The current authors plan to conduct a prospective, randomized, placebo controlled evaluation of stress-dose steroids efficacy with repect to early postresuscitation hemodynamics, heart function, brain perfusion, and inflammatory response in vasopressor-requiring cardiac arrest. Patients will also be followed for organ dysfunction, potential, steroid-associated complications, and functional outcome at hospital discharge.

Conditions

Inhospital Cardiac Arrest

Outcome Measures

Primary Outcomes (10)

• Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring (as Feasible).

  Results on early postresuscitation, mean arterial blood pressure (mmHg) are provided for the first, pre-specified time point of measurement, i.e. at 20 min after the return of spontaneous circulation (ROSC).

  Time point of measurement: 20 min after the return of spontaneous circulation (ROSC).

• Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port (as Feasible).

  Results on early postresuscitation central venous oxygen saturation (%) are provided for the first, pre-specified time point of measurement, I.e., 20 min after the return of spontaneous circulation (ROSC). Actually, and exclusively for this particular measurement, reasons for the failure of consistent data collection are given below.

  Time points of measurement: 20 min after ROSC.

• Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring (as Feasible).

  Results on early postresuscitation, mean arterial blood pressure (mmHg) are provided for the second, pre-specified time point of measurement, i.e. at 4 hours after ROSC.

  Time points of measurement: 4 hours after ROSC.

• Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port (as Feasible).

  Results on postresuscitation central venous oxygen saturation (%) are provided for the second, pre-specified time point of measurement, i.e., at 4 hours after ROSC.

  Time points of measurement: 4 hours after ROSC.

• Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring.

  Results on postresuscitation, mean arterial blood pressure (mmHg) are provided for the third, pre-specified time point of measurement, i.e. at 24 hours after ROSC.

  Time points of measurement: 24 hours after ROSC.

• Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port.

  Results on postresuscitation central venous oxygen saturation (%) are provided for the third, pre-specified time point of measurement, i.e., at 24 hours after ROSC.

  Time points of measurement: 24 hours after ROSC.

• Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring.

  Results on postresuscitation, mean arterial blood pressure (mmHg) are provided for the fourth, pre-specified time point of measurement, i.e. at 48 hours after ROSC.

  Time points of measurement: 48 hours after ROSC.

• Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port.

  Results on postresuscitation central venous oxygen saturation (%) are provided for the fourth, pre-specified time point of measurement, i.e., at 48 hours after ROSC.

  Time points of measurement: 48 hours after ROSC.

• Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring.

  Results on postresuscitation, mean arterial blood pressure (mmHg) are provided for the fifth, pre-specified time point of measurement, i.e. at 72 hours after ROSC.

  Time points of measurement: 72 hours after ROSC.

• Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port.

  Results on postresuscitation central venous oxygen saturation (%) are provided for the fifth, pre-specified time point of measurement, i.e., at 72 hours after ROSC.

  Time points of measurement: 72 hours after ROSC.

Secondary Outcomes (13)

• Left and Right Ventricular Diastolic Area (cm^2) by Echocardiography.

  Time points of measurement: Within the first 12 hours and at 72 hours postresuscitation.

• Left and Right Ventricular Ejection Fraction (%) by Echocardiography.

  Time points of measurement: Within the first 12 hours and at 72 hours postresuscitation.

• Eccentricity Index by Echocardiography.

  Time points of measurement: Within the first 12 hours and at 72 hours postresuscitation.

• Early Postresuscitation Cardiac Output (L/Min) Measured by Either Pulse Index Continuous Cardiac Output (PiCCO) or a Continuous Cardiac Output (CCO) Thermodilution Pulmonary Artery Catheter.

  Time points of measurement: 4 hours after ROSC.

• Early Postresuscitation Cardiac Output (L/Min) Measured by Either Pulse Index Continuous Cardiac Output (PiCCO) or a Continuous Cardiac Output (CCO) Thermodilution Pulmonary Artery Catheter.

  Time points of measurement: 24 hours after ROSC.

Study Arms (2)

Steroids Group

EXPERIMENTAL

Intervention: Stress-dose Steroids. Patients will receive methylprednisolone 40 mg (on the first, postenrollment cardiopulmonary resuscitation cycle. Otherwise, advanced life support will be conducted according to the 2015 guidelines for resuscitation). After resuscitation, patients will be treated with stress-dose hydrocortisone 240 mg daily for 7 days maximum, followed by gradual taper over the next 2 days.

Drug: Methylprednisolone; hydrocortisone

Control Group

PLACEBO COMPARATOR

Intervention: Saline placebo. Patients will receive saline placebo on the first, postenrollment cardiopulmonary resuscitation cycle. Otherwise, advanced life support will be conducted according to the 2015 guidelines for resuscitation. After resuscitation, patients will be treated with saline placebo for a maximum of 9 days (i.e. 7 days corresponding to the stress-dose hydrocortisone treatment of the experimental arm plus 2 days corresponding to the gradual taper of the stress-dose hydrocortisone treatment of the experimental arm).

Drug: Saline Placebo

Interventions

Methylprednisolone; hydrocortisone DRUG

Methylprednisolone 40 mg during resuscitation and stress-dose hydrocortisone for postresuscitation shock

Also known as: Solumedrol; Solucortef

Steroids Group

Saline Placebo DRUG

Saline placebo during resuscitation and during the postresuscitation phase.

Also known as: Isotonic sodium chloride placebo

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 in-patients with ROSC \[for at least 20 min\] after cardiac arrest due to
• Ventricular fibrillation/pulseless tachycardia not responsive to three direct current countershocks, or
• Asystole, or
• Pulseless electrical activity.

You may not qualify if:

• Age \<18 years
• Terminal illness (i.e. life expectancy \<6 weeks e.g. due to metastatic cancer, or Sequential Organ Dysfunction Assessment score of 15 or more, or new septic complication in the presence of immunosuppression) or do-not- resuscitate status
• Cardiac arrest due to exsanguination (e.g. ruptured aortic aneurysm)
• Cardiac arrest before hospital admission
• Pre-arrest treatment with intravenous corticosteroids
• Any history of an allergic reaction
• Transmural myocardial infarction
• Pre-arrest diagnosis of an "active" peptic ulcer. Projected ICU admission time of more than 48 hours in case of a concurrent, special public health circumstance (e.g. severe flu outbreak) that may abruptly increase the demand for intensive care.

Sponsors & Collaborators

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

Study Sites (2)

Department of Intensive Care Medicine, Evaggelismos Hospital

Athens, Attica, GR-10675, Greece

Location

Larisa University General Hospital

Larissa, Thessaly, GR-41110, Greece

Location

Related Publications (23)

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MeSH Terms

Interventions

Methylprednisolone; Hydrocortisone; Methylprednisolone Hemisuccinate

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Limitations and Caveats

1. Occurrence of several protocol breaches, with administration of open label steroids to severely shocked patients of both groups 2. Missing central venous oxygen saturation data for the first time point of measurement (i.e. 20 min after ROSC)

Results Point of Contact

• Title: Associate Professor in Intensive Care Medicine
• Organization: National and Kapodistrian University of Athens

sdmentzelopoulos@yahoo.com

00302132043307

Study Officials

• Spyros D. Mentzelopoulos, MD, PhD

  University of Athens

  PRINCIPAL INVESTIGATOR

• Spyros G. Zakynthinos, MD, PhD

  University of Athens

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: MD, PhD, DEAA, EDIC, Associate Professor of Intensive Care Medicine

Study Record Dates

• First Submitted: May 24, 2016
• First Posted: June 6, 2016
• Study Start: November 4, 2016
• Primary Completion: May 22, 2018
• Study Completion: August 11, 2018
• Last Updated: November 23, 2021
• Results First Posted: November 18, 2019

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

GR (2)