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CompletedNCT02790788CORTICAUpdated Nov 23, 2021Results posted

Physiologic Effects of Steroids in Cardiac Arrest

A Phase 1/2 interventional study of Methylprednisolone; hydrocortisone and Saline Placebo in Inhospital Cardiac Arrest, sponsored by University of Athens. Completed at 2 sites in Greece. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-11-23.

Sponsored by University of Athens · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
100
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

BACKGROUND AND RATIONALE Despite recent improvements in the quality of care, in-hospital cardiac arrest is still associated with a high probability of poor outcome. Patients resuscitated from vasopressor-requiring cardiac arrest frequently exhibit early postresuscitation hemodynamic instability that is poorly responsive to hemodynamic support with high vasopressor doses and intravenous fluids titrated to cardiac filling pressures of at least 12 mmHg. Furthermore, preceding studies indicate that postresuscitation disease is a "sepsis-like" syndrome characterized by plasma cytokine elevation, endotoxemia, coagulopathy and adrenal insufficiency contributing to postresuscitation shock. Steroids are currently being used for improving hemodynamics in septic patients, however, their effect on postresuscitation hemodynamics has not been thoroughly elucidated yet.

OBJECTIVES To determine whether stress-dose steroid supplementation during and after cardiopulmonary resuscitation (CPR) improves the hemodynamic parameters (arterial blood pressure, cardiac output, cerebral blood flow) in patients with in-hospital cardiac arrest. Furthermore to study the effects of steroid administration on the inflammatory response and organ failures, and to determine potential, corticosteroid-associated complications such as hyperglycemia, infections, bleeding peptic ulcers and paresis. In summary, we aim to directly assess the physiological effects and safety of steroids during and after CPR. The possible clinical usefulness of steroids during and after CPR - in the context of early postresuscitation hemodynamic support - currently corresponds to an important knowledge gap, as recently acknowledged by Guidelines Evidence Reviewers.

METHODS SETTING Intensive/coronary care units, (ICUs/CCUs) of the Evaggelismos Hospital, Athens, Greece (1,200 beds) and of the Larissa University Hospital, Larissa, Greece (700 beds).

PATIENTS

Inclusion criteria:

Patients who have experienced an in-hospital, vasopressor-requiring cardiac arrest, according to guidelines for resuscitation from 2015.

Exclusion criteria are reported in the dedicated subsection.

ETHICS AND INFORMED CONSENT The study will be conducted in concordance with European Union Clinical Trials Regulation No 536/2014 and the Helsinki Declaration. Due to the emergency situation, consent will not be requested for steroid supplementation during CPR. The patients' families and patients who regain consciousness and communication ability during follow-up will be informed about the study as soon as possible, and any objection will result in exclusion of the patient data from any subsequent analyses. Informed, written next-of-kin consent and non-written patient consent (whenever feasible) will be requested as soon as possible for stress-dose hydrocortisone in postresuscitation shock and continued participation in the study. If consent cannot obtained before patient death, the patient's next of kin will be informed of the study and their permission for inclusion of the patient data in the subsequent analyses will be requested. All consent procedures will additionally be documented on the patient's medical record.

The original protocol version has been approved by the Institutional Review Board (IRB) of Evaggelismos General Hospital on July 14 2016 (Approval No. 126/16-6-2016), and by the IRB of Larissa University Hospital on October 10, 2016 (Approval No. 46113/11-10-2016 - IRB Discussion No. 13/10-10-2016 Θ.6). Subsequent protocol amendments have been approved by the Evaggelismos IRB on January 24, 2017 (Approval No. 8/26-1-2017), and this has been communicated to the IRB of Larissa University Hospital.

STUDY DESIGN We propose a prospective, randomized, double-blind, placebo-controlled, parallel- group clinical trial.

RANDOMIZATION Research Randomizer version 4 (https://www.randomizer.org/) will be used by the study statistician for group allocation. For each study center, random numbers (range, 1-100) will be generated in sets of 4. Each random number of each set will be unique and correspond to 1 of the consecutively enrolled patients. In each set, an odd or even first number will result in assignment of the corresponding patient to the control or steroids group, respectively. In each study center, the group allocation rule will be known solely by the pharmacists who will prepare the study drugs.

CPR AND POSTRESUSCITATION INTERVENTIONS We will enrol adult in-patients with cardiac arrest due to ventricular fibrillation/pulseless tachycardia not responsive to three direct current countershocks, or asystole, or pulseless electrical activity. Study treatments will be administered during the first CPR cycle postenrollment. Patients will be randomized to receive either methylprednisolone 40 mg (Steroids group) or normal saline placebo (Control group) on the first, postenrollment CPR cycle. Otherwise, advanced life support will be conducted according to the 2015 guidelines for resuscitation. After resuscitation, patients will be treated with either stress-dose hydrocortisone of 240 mg daily for 7 days maximum (Steroids group), or saline placebo (Control group). More specifically, at 4 hours after ROSC, patients will receive 100 mL/day (average pump infusion rate \~ 4.2 mL/h) of normal saline that will either contain the stress-dose of hydrocortisone (Steroids group) or solely saline placebo (Control group) for a maximum of 9 days. On days 8 and 9 the hydrocortisone dose of the Steroids group will be tapered to 120 mg and 60 mg, respectively, and finally discontinued on day 10 postrandomization. On ICU/CCU admission, patients will receive a central venous line, and an arterial line, either standard or as part of pulsatility index continuous cardiac output monitoring. Patients with a standard arterial line will also receive a pulmonary artery catheter, provided that attending physicians also agree to this.

DOCUMENTATION AND PATIENT FOLLOW-UP CPR attempts will be documented according to the Utstein style. Hemodynamics and gas-exchange, electrolytes, glucose, central body temperature, lactate and administered fluids and vasopressor/inotropic support will be determined/recorded during CPR, and at \~20 min and \~4 hours as well as at 24, 48 and 72 hours after the return of spontaneous circulation (ROSC); ROSC will be defined as sustained presence of a palpable arterial pulse for at least 20 min. Postresuscitation cardiac output will be monitored for at least 72 hours post-ROSC, and postresuscitation cardiac function will be assessed by ultrasonography within the first hour after ICU admission and at 72 hours post-ROSC. Central-venous blood gas analysis will also be performed at the aforementioned time points and blood samples will be taken for the determination of cytokines at approximately 20 min and 4, 24, 48, and 72 hours post-ROSC.

Follow-up during the first 10 days postrandomization will include 1) Determination/recording of hemodynamics and hemodynamic support, gas-exchange, fluid balance of the preceding 24 hours, and arterial blood lactate and central venous oxygen saturation at 9 a.m.; 2) Daily determinations of serum pro-inflammatory cytokines, and 3) Daily recording (within 8-9 a.m.) of laboratory data, and prescribed medication.

The results of 4 daily determinations (1 every 6 hours) of blood glucose will also be recorded to subsequently analyze the incidence of hyperglycemia (blood glucose exceeding 200 mg/dL -11.1 mmol/L). Follow-up to day 60 post-ROSC will include organ failures, and ventilator-free days. Morbidity/complications throughout ICU/CCU and hospital stay, and times to ICU/CCU and hospital discharge will also be recorded.

Study outcomes are reported in the dedicated subsection.

PROTOCOL AMENDMENTS [Approved, January 24, 2017]

Amendment: 1. Part A: Postresuscitation Cardiac Output (CO) has been moved from the primary to the secondary study outcomes (see also Outcome Measures' subsection). Reason for amendment: We ultimately anticipate to be able to collect such data in \<50% of the patients. Part B: Furthermore, the measurement time point of "8 hours postresuscitation" will no longer be part of the protocol and this will apply for the total of the physiological measurements. This aims to limit attending investigator workload.

Amendment 2: Further clarification regarding the "acceptable" time frame for ICU / CCU admission of successfully resuscitated patients. This is a very important logistical issue and will include measures (e.g. monitoring and medical service support and oversight) to optimize the quality of care until ICU admission and the specification of the "maximum acceptable time to ICU admission". In the VSE 1 and 2 studies, this time has been 12 hours. During 2016, the Evaggelismos Department of Intensive Care Medicine has experienced a reduction of 5 ICU beds (i.e. from 30 to 25) and 8 HDU (high-dependency unit) beds from 20 to 12. Therefore, regarding cardiac arrest patients, we have decided to extend the target time limit for admission to 24 hours. Regarding CORTICA, any further delay is to be reported as an "unpreventable" protocol breach, and in the case of a possible extreme circumstance (e.g. a severe flu outbreak), any patients with a projected ICU admission time of more than 48 hours will be excluded. Hence, "a projected ICU admission time of more than 48 hours" will constitute an additional exclusion criterion.

Amendment 3: Further clarification of the "terminal illness" exclusion criterion - life expectancy of no more than 6 weeks): (i) Patients with metastatic cancer [with confirmed bone and/or brain metastases], and/or primary / metastatic disease causing respiratory failure with/without additional organ-system failures [as defined by a corresponding Sequential Organ Dysfunction Assessment (SOFA) subscore of 3 or 4]; (ii) Patients with a pre-arrest worst SOFA score of >=15 (this corresponds to a probability of death of at least 90%); and (ii) Patients with immunosuppression and a new, hospital-acquired septic complication).

Amendment 4: Addition of the following Exclusion Criterion: "Any deviation from the hospital's standard resuscitative procedure" (e.g. poor adherence to the standard Advanced Life Support algorithm such as an epinephrine dosing error or use of atropine, or "unjustified" interruption of chest compressions compromising CPR quality).

Amendment 5: Addition of the following Exclusion Criterion: Pre-arrest diagnosis of an "active" peptic ulcer; that is, either preceding gastroscopic confirmation of a peptic ulcer, or clinical evidence of acute, pre-arrest gastrointestinal bleeding, attributable to peptic ulcer disease.

Amendment 6: Follow-up during the first 10 days: The time of determination of cytokines will be 20 min, 4, 24, 48, and 72 hours post ROSC [as specified in the corresponding outcome measure], and 7 days post-ROSC (that is, the determinations of day 4, 5, 6, 8, 9, and 10 will be cancelled); Reason for change: Study cost reduction.

Amendment 7: An amendment of the statistical analysis plan enabling the inclusion of patients without return of spontaneous circulation (ROSC) was approved by the Evaggelismos Hospital IRB (Approval No. 527/11-11-2021), and by the Larissa University Hospital IRB (Approval No. 44243/10-11-2021. The rationale for this amendment pertained to the prevention of bias due to post-randomization exclusion. The amendment was actually prompted by a relevant peer review comments.

STATISTICS Data will be reported as mean±standard deviation, or median (interquartile range), or number (percentage), unless otherwise specified. Distribution normality will be tested by Kolmogorov-Smirnov test. Dichotomous and categorical variables will be compared by two-sided chi-square or Fisher's exact test. Continuous variables will be compared by two-tailed, independent samples t test or Mann-Whitney exact U test. P- values of multiple t-test comparisons will be subjected to the Bonferroni correction. We will use mixed model analysis to compare repeatedly measured variables between the two groups. Survival data will be analyzed by a previously employed methodology of multivariable Cox regression. Based on previously published data on the mean arterial pressure at 24 hours postresuscitation, to detect an effect size d of 0.761 with an α error probability of 0.015 and power 0.80, we need to enroll a total of 78 patients (39 in each group). A target enrollment of 100 patients with ROSC for at least 20 min will likely adequately compensate for possible dropouts or missing data. Expected results pertain to a steroid-associated benefit with respect to the primary outcomes, consistent with results on secondary outcomes.

02

Conditions studied

  • Inhospital Cardiac Arrest

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03

In context

Heart Arrest

966 studies on the registry are indexed under Heart Arrest; 227 are open to participants now.

This study's enrollment of 100 is close to the median of 100 across 557 interventional studies indexed under Heart Arrest.

Browse Heart Arrest studies →

Lead sponsor

University of Athens is the lead sponsor of 133 studies on the registry; 19 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

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.

Exclusion criteria

Exclusion Criteria:

  • 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
  • Previous enrollment in or exclusion from the current study.
  • Confirmation of return of spontaneous circulation before study-drug administration, corresponding to "premature randomization" [reference 18] will also result in patient exclusion due to absence of vasopressor-requiring cardiac arrest.

Additional Exclusion Criteria According to the Protocol Amendment approved on January 24, 2017: Any deviation from the hospital's standard resuscitative procedure.

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.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
100 participants (actual)

Study arms

  • Experimental
    Steroids Group

    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

  • Placebo comparator
    Control Group

    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

  • DrugMethylprednisolone; hydrocortisone

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

    Also known as: Solumedrol; Solucortef

  • DrugSaline Placebo

    Saline placebo during resuscitation and during the postresuscitation phase.

    Also known as: Isotonic sodium chloride placebo

06

What researchers measure

Primary outcomes

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

  2. 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 frame: Time points of measurement: 20 min after ROSC.

  3. 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 frame: Time points of measurement: 4 hours after ROSC.

  4. 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 frame: Time points of measurement: 4 hours after ROSC.

  5. 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 frame: Time points of measurement: 24 hours after ROSC.

  6. 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 frame: Time points of measurement: 24 hours after ROSC.

  7. 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 frame: Time points of measurement: 48 hours after ROSC.

  8. 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 frame: Time points of measurement: 48 hours after ROSC.

  9. 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 frame: Time points of measurement: 72 hours after ROSC.

  10. 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 frame: Time points of measurement: 72 hours after ROSC.

Secondary outcomes

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

    Results are provided on left ventricular end-diastolic area (LVEDA) and right ventricular diastolic area (RVEDA) by echocardiography within 12 hours and 72 hours after ROSC.

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

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

    Results are provided on left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) within 12 hours and 72 hours after ROSC.

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

  3. Eccentricity Index by Echocardiography.

    Eccentricity index (ECCI) is defined as the ratio of the left ventricular (LV) "longitudinal" (or anteroposterior) diameter to the LV "transverse" (or septo-lateral) diameter, measured at end diastole and end systole in a short-axis view. Pertinent results are provided for a first determination within 12 hours after ROSC and a second determination at 72 hours after ROSC.

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

  4. 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.

    RESULTS ARE PROVIDED FOR CARDIAC OUTPUT (CO) AT 4 HOURS AFTER ROSC.

    Time frame: Time points of measurement: 4 hours after ROSC.

  5. 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.

    Results are provided for CO at 24 hours after ROSC.

    Time frame: Time points of measurement: 24 hours after ROSC.

  6. 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.

    Results are provided for CO at 48 hours after ROSC

    Time frame: Time points of measurement: 48 hours after ROSC.

  7. 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.

    Results are provided for CO at 72 hours after ROSC.

    Time frame: Time points of measurement: 72 hours after ROSC.

  8. Core Body Temperature in Degrees Celcius.

    Results are provided for core body temperature averaged over the following time intervals after ROSC: 1) 0-6 hours; 2) 6-12 hours; 3) 12-18 hours; 4) 18-24 hours; 5) 24-30 hours; 6) 30-36 hours; 7) 36-42 hours; and 42-48 hours.

    Time frame: Time points of measurement: Hourly from intensive care admission to 48 hours postresuscitation.

  9. Cerebral Blood Flow Index by Near Infrared Spectroscopy With Indocyanine Green.

    Results are reported for 2 pairs of cerebral blood flow index (CBFI) measurements performed each time at a lower and a higher level of mean arterial pressure (MAP) at the following time points: 1) at 4 hours after ROSC and 2) at 72 hours after ROSC

    Time frame: Time points of measurement: 4 and 72 hours postresuscitation.

  10. Organ Failure-free Days.

    Number of organ failure-free days during days 1 through 60 postrandomization. Organ failure free=corresponding Sequential Organ Failure Assessment Subscore \<3; each subscore can have the following values: 0, 1, 2, 3, and 4; increasing values indicate worsening organ failure.

    Time frame: Days 1 to 60 postrandomization.

  11. Early Postresuscitation Inflammatory Response as Assessed by Serum Cytokine Levels (pg/mL).

    Logarithm (base 10)-transformed serum levels of tumor necrosis factor alpha (TNFa), interleukin (IL)-1 beta, IL-6, IL-8, and IL-10; blood samples were obtained by venipuncture.

    Time frame: Time points of measurement: 4, 24, 48, and 72 hours postresuscitation.

  12. Survival to Hospital Discharge With Favorable Functional Outcome.

    Survival to hospital discharge with a Cerebral Performance Category (CPC) Score of 1 or 2. The CPC Score ranges can have the following values: 1, 2, 3, 4, and 5; lower Scores correspond to better outcomes, whereas higher Scores reflect worsening outcomes, e.g. a Score of 4 means Coma or Vegetative state, and a Score of 5 means Brain Death.

    Time frame: Up to 180 days postrandomization.

  13. Steroid-associated Complications.

    Episodes of 1) Hyperglycemia (defined as Blood Glucose \>200 mg/dL), 2) Hypernatremia (defined as blood gas analysis-derived sodium ion concentration \>150 mEq/L), and 3) Infections (defined as any microbiologically documented, intensive care unit-acquired, or hospital-acquired infection).

    Time frame: Up to 180 days postrandomization.

07

Results

Posted Nov 18, 2019
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)

Participant flow

Participant flow — Overall Study
MilestoneSteroids GroupControl Group
Started4654
Completed4654
Not completed00

Outcome measures

PrimaryEarly 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 frame:
Time point of measurement: 20 min after the return of spontaneous circulation (ROSC).
Reported as:
Mean · mmHg
Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring (as Feasible).
mmHgSteroids GroupControl Group
Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring (as Feasible).78.4 ± 21.375.1 ± 21.4
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.44 · Mean difference (net): 3.3 · 95% CI -5.2 to 11.8
PrimaryEarly 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 frame:
Time points of measurement: 20 min after ROSC.

No measurements were reported for this outcome.

PrimaryEarly 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 frame:
Time points of measurement: 4 hours after ROSC.
Reported as:
Mean · mmHg
Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring (as Feasible).
mmHgSteroids GroupControl Group
Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring (as Feasible).83.9 ± 18.178.9 ± 15.6
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.17 · Mean difference (net): 5.0 · 95% CI -2.2 to 12.2
PrimaryEarly 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 frame:
Time points of measurement: 4 hours after ROSC.
Reported as:
Mean · Percent Hemoglobin Concentration
Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port (as Feasible).
Percent Hemoglobin ConcentrationSteroids GroupControl Group
Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port (as Feasible).67.4 ± 10.256.8 ± 22.7
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.043 · Mean difference (final values): 10.6 · 95% CI 0.4 to 20.8
PrimaryEarly 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 frame:
Time points of measurement: 24 hours after ROSC.
Reported as:
Mean · mmHg
Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring.
mmHgSteroids GroupControl Group
Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring.79.9 ± 16.081.9 ± 15.2
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.59 · Mean difference (net): -2.0 · 95% CI -9.3 to 5.3
PrimaryEarly 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 frame:
Time points of measurement: 24 hours after ROSC.
Reported as:
Mean · Percent Hemoglobin Concentration
Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port.
Percent Hemoglobin ConcentrationSteroids GroupControl Group
Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port.71.1 ± 8.570.1 ± 8.3
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.64 · Mean difference (net): 1.0 · 95% CI -3.1 to 5.0
PrimaryEarly 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 frame:
Time points of measurement: 48 hours after ROSC.
Reported as:
Mean · mmHg
Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring.
mmHgSteroids GroupControl Group
Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring.80.2 ± 10.084.2 ± 13.6
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.20 · Mean difference (net): -4.0 · 95% CI -10.1 to 2.1
PrimaryEarly 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 frame:
Time points of measurement: 48 hours after ROSC.
Reported as:
Mean · Percent Hemoglobin Concentration
Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port.
Percent Hemoglobin ConcentrationSteroids GroupControl Group
Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port.73.3 ± 8.070.5 ± 6.5
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.14 · Mean difference (net): 2.8 · 95% CI -0.9 to 6.6
PrimaryEarly 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 frame:
Time points of measurement: 72 hours after ROSC.
Reported as:
Mean · mmHg
Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring.
mmHgSteroids GroupControl Group
Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring.85.2 ± 11.684.7 ± 14.5
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.90 · Mean difference (net): 0.5 · 95% CI -6.4 to 7.3
PrimaryEarly 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 frame:
Time points of measurement: 72 hours after ROSC.
Reported as:
Mean · Percent Hemoglobin Saturation
Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port.
Percent Hemoglobin SaturationSteroids GroupControl Group
Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port.72.5 ± 9.570.4 ± 7.1
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.33 · Mean difference (net): 2.1 · 95% CI -2.2 to 6.4
SecondaryLeft and Right Ventricular Diastolic Area (cm^2) by Echocardiography.

Results are provided on left ventricular end-diastolic area (LVEDA) and right ventricular diastolic area (RVEDA) by echocardiography within 12 hours and 72 hours after ROSC.

Time frame:
Time points of measurement: Within the first 12 hours and at 72 hours postresuscitation.
Reported as:
Mean · cm^2
Left and Right Ventricular Diastolic Area (cm^2) by Echocardiography.
cm^2Steroids GroupControl Group
LVEDA within 12 hours after ROSC23.1 ± 9.122.8 ± 8.2
RVEDA within 12 hours after ROSC12.1 ± 4.313.0 ± 4.0
LVEDA at 72 hours after ROSC23.1 ± 7.918.5 ± 2.9
RVEDA at 72 hours after ROSC14.5 ± 3.712.6 ± 4.1
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.92 · Mean difference (net): 0.3 · 95% CI -5.3 to 5.8
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.54 · Mean difference (net): -0.81 · 95% CI -3.4 to 1.8
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.048 · Mean difference (net): 4.60 · 95% CI 0.04 to 9.15
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.18 · Mean difference (net): 1.9 · 95% CI -1.0 to 4.7
SecondaryLeft and Right Ventricular Ejection Fraction (%) by Echocardiography.

Results are provided on left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) within 12 hours and 72 hours after ROSC.

Time frame:
Time points of measurement: Within the first 12 hours and at 72 hours postresuscitation.
Reported as:
Mean · Percentage
Left and Right Ventricular Ejection Fraction (%) by Echocardiography.
PercentageSteroids GroupControl Group
LVEF within 12 hours after ROSC42.3 ± 14.145.9 ± 13.2
RVEF within 12 hours after ROSC41.7 ± 8.742.7 ± 9.3
LVEF at 72 hours after ROSC45 ± 11.850 ± 9.4
RVEF at 72 hours after ROSC42.8 ± 8.444.7 ± 7.1
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.32 · Mean difference (net): -3.6 · 95% CI -10.9 to 3.7
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.76 · Mean difference (net): -1.0 · 95% CI -7.2 to 5.3
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.25 · Mean difference (net): -4.9 · 95% CI -13.5 to 3.7
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.61 · Mean difference (net): -1.8 · 95% CI -9.1 to 5.5
SecondaryEccentricity Index by Echocardiography.

Eccentricity index (ECCI) is defined as the ratio of the left ventricular (LV) "longitudinal" (or anteroposterior) diameter to the LV "transverse" (or septo-lateral) diameter, measured at end diastole and end systole in a short-axis view. Pertinent results are provided for a first determination within 12 hours after ROSC and a second determination at 72 hours after ROSC.

Time frame:
Time points of measurement: Within the first 12 hours and at 72 hours postresuscitation.
Reported as:
Mean · ECCENTRICITY INDEX
Eccentricity Index by Echocardiography.
ECCENTRICITY INDEXSteroids GroupControl Group
End-diastolic ECCI within 12 hours after ROSC1.2 ± 0.31.3 ± 0.3
End-systolic ECCI within 12 hours after ROSC1.3 ± 0.31.3 ± 0.3
End-diastolic ECCI at 72 hours after ROSC1.2 ± 0.21.3 ± 0.3
End-systolic ECCI at 72 hours after ROSC1.2 ± 0.31.3 ± 0.4
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.41 · Mean difference (net): -0.07 · 95% CI -0.25 to 0.11
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.38 · Mean difference (net): -0.08 · 95% CI -0.26 to 0.10
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.46 · Mean difference (net): -0.08 · 95% CI -0.29 to 0.14
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.34 · Mean difference (net): -0.11 · 95% CI -0.33 to 0.12
SecondaryEarly Postresuscitation Cardiac Output (L/Min) Measured by Either Pulse Index Continuous Cardiac Output (PiCCO) or a Continuous Cardiac Output (CCO) Thermodilution Pulmonary Artery Catheter.

RESULTS ARE PROVIDED FOR CARDIAC OUTPUT (CO) AT 4 HOURS AFTER ROSC.

Time frame:
Time points of measurement: 4 hours after ROSC.
Reported as:
Mean · L/min
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.
L/minSteroids GroupControl Group
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.4.9 ± 1.05.0 ± 2.0
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.90 · Mean difference (net): -0.10 · 95% CI -1.5 to 1.3
SecondaryEarly Postresuscitation Cardiac Output (L/Min) Measured by Either Pulse Index Continuous Cardiac Output (PiCCO) or a Continuous Cardiac Output (CCO) Thermodilution Pulmonary Artery Catheter.

Results are provided for CO at 24 hours after ROSC.

Time frame:
Time points of measurement: 24 hours after ROSC.
Reported as:
Mean · L/min
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.
L/minSteroids GroupControl Group
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.5.6 ± 1.65.4 ± 1.2
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.59 · Mean difference (net): 0.20 · 95% CI -0.54 to 0.94
SecondaryEarly Postresuscitation Cardiac Output (L/Min) Measured by Either Pulse Index Continuous Cardiac Output (PiCCO) or a Continuous Cardiac Output (CCO) Thermodilution Pulmonary Artery Catheter.

Results are provided for CO at 48 hours after ROSC

Time frame:
Time points of measurement: 48 hours after ROSC.
Reported as:
Mean · L/min
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.
L/minSteroids GroupControl Group
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.5.8 ± 1.65.7 ± 1.3
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.67 · Mean difference (net): 0.17 · 95% CI -0.60 to 0.93
SecondaryEarly Postresuscitation Cardiac Output (L/Min) Measured by Either Pulse Index Continuous Cardiac Output (PiCCO) or a Continuous Cardiac Output (CCO) Thermodilution Pulmonary Artery Catheter.

Results are provided for CO at 72 hours after ROSC.

Time frame:
Time points of measurement: 72 hours after ROSC.
Reported as:
Mean · L/min
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.
L/minSteroids GroupControl Group
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.5.8 ± 1.85.6 ± 1.3
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.65 · Mean difference (net): 0.19 · 95% CI -0.64 to 1.02
SecondaryCore Body Temperature in Degrees Celcius.

Results are provided for core body temperature averaged over the following time intervals after ROSC: 1) 0-6 hours; 2) 6-12 hours; 3) 12-18 hours; 4) 18-24 hours; 5) 24-30 hours; 6) 30-36 hours; 7) 36-42 hours; and 42-48 hours.

Time frame:
Time points of measurement: Hourly from intensive care admission to 48 hours postresuscitation.
Reported as:
Mean · Degrees Celcius
Core Body Temperature in Degrees Celcius.
Degrees CelciusSteroids GroupControl Group
Temperature averaged over 0-6 hours after ROSC36.5 ± 1.135.6 ± 5.7
Temperature averaged over 6-12 hours after ROSC36.3 ± 1.036.6 ± 1.3
Temperature averaged over 12-18 hours after ROSC36.0 ± 1.036.5 ± 1.1
Temperature averaged over 18-24 hours after ROSC36.1 ± 1.536.3 ± 0.9
Temperature averaged over 24-30 hours after ROSC36.1 ± 1.136.2 ± 1.0
Temperature averaged over 30-36 hours after ROSC36.0 ± 1.136.2 ± 1.2
Temperature averaged over 36-42 hours after ROSC36.1 ± 1.036.2 ± 1.2
Temperature averaged over 42-48 hours after ROSC36.2 ± 1.036.3 ± 1.1
Statistical analysis
  • Steroids Group · t-test, 2 sided · p = 0.41 (RESULTS CORRESPOND TO CORE BODY TEMPERATURE AVERAGED OVER 0-6 HOURS AFTER ROSC.) · Mean difference (net): 0.8 · 95% CI -1.2 to 2.8
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.20 · Mean difference (net): -0.36 · 95% CI -0.92 to 0.19
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.07 · Median difference (net): -0.48 · 95% CI -1.00 to 0.04
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.36 · Mean difference (net): -0.27 · 95% CI -0.85 to 0.31
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.54 · Median difference (net): -0.16 · 95% CI -0.66 to 0.35
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.62 · Mean difference (net): -0.14 · 95% CI -0.69 to 0.42
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.60 · Mean difference (net): -0.15 · 95% CI -0.71 to 0.41
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.54 · Median difference (net): -0.16 · 95% CI -0.69 to 0.36
SecondaryCerebral Blood Flow Index by Near Infrared Spectroscopy With Indocyanine Green.

Results are reported for 2 pairs of cerebral blood flow index (CBFI) measurements performed each time at a lower and a higher level of mean arterial pressure (MAP) at the following time points: 1) at 4 hours after ROSC and 2) at 72 hours after ROSC

Time frame:
Time points of measurement: 4 and 72 hours postresuscitation.
Reported as:
Mean · nM/s
Cerebral Blood Flow Index by Near Infrared Spectroscopy With Indocyanine Green.
nM/sSteroids GroupControl Group
CBFI 4 HOURS POST-ROSC MEAN MAP=75.5 MMHG4.0 ± 2.53.3 ± 2.1
CBFI 4 HOURS POST-ROSC MEAN MAP=96.0 MMHG4.2 ± 2.33.5 ± 1.9
CBFI 72 HOURS POST-ROSC MEAN MAP=75.5 MMHG4.3 ± 3.53.4 ± 2.2
CBFI 72 HOURS POST-ROSC MEAN MAP= 97.0 MMHG4.9 ± 3.83.8 ± 2.4
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.42 · Mean difference (net): 0.71 · 95% CI -2.5 to 1.1
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.40 · Median difference (net): 0.68 · 95% CI -0.94 to 2.30
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.44 · Mean difference (net): 0.90 · 95% CI -1.49 to 3.28
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.36 · Median difference (net): 1.15 · 95% CI -1.40 to 3.70
SecondaryOrgan Failure-free Days.

Number of organ failure-free days during days 1 through 60 postrandomization. Organ failure free=corresponding Sequential Organ Failure Assessment Subscore \<3; each subscore can have the following values: 0, 1, 2, 3, and 4; increasing values indicate worsening organ failure.

Time frame:
Days 1 to 60 postrandomization.
Reported as:
Median · Number of Days without Organ Failure
Organ Failure-free Days.
Number of Days without Organ FailureSteroids GroupControl Group
Organ Failure-free Days.0 (0 to 13)0 (0 to 13)
Statistical analysis
  • Steroids Group vs Control Group · Mann Whitney · p = 0.84
SecondaryEarly Postresuscitation Inflammatory Response as Assessed by Serum Cytokine Levels (pg/mL).

Logarithm (base 10)-transformed serum levels of tumor necrosis factor alpha (TNFa), interleukin (IL)-1 beta, IL-6, IL-8, and IL-10; blood samples were obtained by venipuncture.

Time frame:
Time points of measurement: 4, 24, 48, and 72 hours postresuscitation.
Reported as:
Mean · Log(10) transformed values of pg/mL
Early Postresuscitation Inflammatory Response as Assessed by Serum Cytokine Levels (pg/mL).
Log(10) transformed values of pg/mLSteroids GroupControl Group
IL-6 at 4 hours after ROSC2.19 ± 0.652.22 ± 0.57
TNFα at 4 hours after ROSC1.97 ± 0.472.03 ± 0.47
IL-1β at 4 hours after ROSC2.07 ± 0.242.03 ± 0.21
IL-8 at 4 hours after ROSC2.39 ± 0.362.43 ± 0.50
IL-10 at 4 hours after ROSC1.76 ± 0.621.76 ± 0.76
IL-6 at 24 hours after ROSC2.06 ± 0.431.99 ± 0.55
TNFα at 24 hours after ROSC2.02 ± 0.482.00 ± 0.51
IL-1β at 24 hours after ROSC2.06 ± 0.132.09 ± 0.91
IL-8 at 24 hours after ROSC2.27 ± 0.412.29 ± 0.45
IL-10 at 24 hours after ROSC1.69 ± 0.621.54 ± 0.65
IL-6 at 48 hours after ROSC1.87 ± 0.351.91 ± 0.51
TNFα at 48 hours after ROSC1.99 ± 0.501.96 ± 0.50
IL-1β at 48 hours after ROSC2.09 ± 0.132.03 ± 0.16
IL-8 at 48 hours after ROSC2.15 ± 0.372.17 ± 0.41
IL-10 at 48 hours after ROSC1.56 ± 0.441.53 ± 0.44
IL-6 at 72 hours after ROSC1.93 ± 0.731.90 ± 0.47
TNFα at 72 hours after ROSC2.00 ± 0.561.96 ± 0.51
IL-1β at 72 hours after ROSC2.05 ± 0.172.04 ± 0.12
IL-8 at 72 hours after ROSC2.15 ± 0.382.19 ± 0.32
IL-10 at 72 hours after ROSC1.66 ± 0.611.45 ± 0.48
Statistical analysis
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.86 · Mean difference (net): -0.025 · 95% CI -0.311 to 0.262
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.56 · Mean difference (net): -0.064 · 95% CI -0.287 to 0.158
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.52 · Mean difference (net): 0.034 · 95% CI -0.071 to 0.139
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.70 · Mean difference (net): -0.041 · 95% CI -0.254 to 0.172
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.97 · Mean difference (net): 0.007 · 95% CI -0.326 to 0.340
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.61 · Median difference (net): 0.067 · 95% CI -0.192 to 0.326
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.91 · Mean difference (net): 0.014 · 95% CI -0.238 to 0.267
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.19 · Mean difference (net): -0.040 · 95% CI -0.100 to 0.021
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.85 · Mean difference (net): -0.022 · 95% CI -0.244 to 0.201
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.37 · Mean difference (net): 0.147 · 95% CI -0.179 to 0.473
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.74 · Mean difference (net): -0.043 · 95% CI -0.298 to 0.212
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.80 · Mean difference (net): 0.036 · 95% CI -0.246 to 0.318
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.20 · Mean difference (net): 0.056 · 95% CI -0.030 to 0.142
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.83 · Mean difference (net): -0.024 · 95% CI -0.246 to 0.198
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.83 · Mean difference (net): 0.027 · 95% CI -0.223 to 0.276
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.85 · Mean difference (net): 0.030 · 95% CI -0.294 to 0.354
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.74 · Mean difference (net): 0.048 · 95% CI -0.243 to 0.339
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.75 · Median difference (net): 0.013 · 95% CI -0.066 to 0.091
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.64 · Mean difference (net): -0.045 · 95% CI -0.238 to 0.149
  • Steroids Group vs Control Group · t-test, 2 sided · p = 0.23 · Mean difference (net): 0.179 · 95% CI -0.116 to 0.475
SecondarySurvival to Hospital Discharge With Favorable Functional Outcome.

Survival to hospital discharge with a Cerebral Performance Category (CPC) Score of 1 or 2. The CPC Score ranges can have the following values: 1, 2, 3, 4, and 5; lower Scores correspond to better outcomes, whereas higher Scores reflect worsening outcomes, e.g. a Score of 4 means Coma or Vegetative state, and a Score of 5 means Brain Death.

Time frame:
Up to 180 days postrandomization.
Reported as:
Count of participants · Participants
Survival to Hospital Discharge With Favorable Functional Outcome.
ParticipantsSteroids GroupControl Group
Survival to Hospital Discharge With Favorable Functional Outcome.25
Statistical analysis
  • Steroids Group vs Control Group · Fisher Exact · p = 0.45 · Percent difference: 4.9 · 95% CI -4.8 to 14.6
SecondarySteroid-associated Complications.

Episodes of 1) Hyperglycemia (defined as Blood Glucose \>200 mg/dL), 2) Hypernatremia (defined as blood gas analysis-derived sodium ion concentration \>150 mEq/L), and 3) Infections (defined as any microbiologically documented, intensive care unit-acquired, or hospital-acquired infection).

Time frame:
Up to 180 days postrandomization.
Reported as:
Median · Number of Episodes per Patient
Steroid-associated Complications.
Number of Episodes per PatientSteroids GroupControl Group
No. of Episodes of Hyperglycemia0 (0 to 2)0 (0 to 2)
No. of Episodes of Hypernatremia0 (0 to 0)0 (0 to 0)
No. of Episodes of Infections0 (0 to 1)0 (0 to 1)
Statistical analysis
  • Steroids Group vs Control Group · Mann Whitney · p = 0.68 · Mann-whitney u: 50903.500
  • Steroids Group vs Control Group · Mann-Whitney · p = 0.68 · Mann whitney u: 52188.5
  • Steroids Group vs Control Group · Mann-Whitney · p = 0.37 · Mann-whitney u: 1128.5

Adverse events

Collected over 180 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Steroids Group45/46 (97.8%)45/46 (97.8%)23/46 (50%)
Control Group53/54 (98.1%)53/54 (98.1%)33/54 (61.1%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventSteroids GroupControl Group
Second Cardiac ArrestGeneral disorders44/4649/54
Cardiac arrest associated multiple organ failureGeneral disorders19/4620/54
Sepsis / Septic ShockInfections and infestations18/4617/54
Hospital acquired pneumoniaInfections and infestations11/469/54
Acute Kidney Injury / Renal FailureGeneral disorders7/4610/54
Severe ThrombocytopeniaBlood and lymphatic system disorders6/465/54
OtherGeneral disorders5/466/54
Acute Respiratory Distress SyndromeRespiratory, thoracic and mediastinal disorders4/462/54
ParesisMusculoskeletal and connective tissue disorders3/462/54
New life-threatening arrhythmiaGeneral disorders2/463/54
Most frequent other events
Most frequent other events
EventSteroids GroupControl Group
HYPERGLYCEMIAGeneral disorders23/4633/54

Baseline characteristics

Descriptive Statistics

Age, Continuous
Age, Continuous(Years)Steroids GroupControl GroupTotal
Mean70.1 ± 19.273.2 ± 12.372.1 ± 15.7
Sex: Female, Male
Sex: Female, Male(Participants)Steroids GroupControl GroupTotal
Female192544
Male272956
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Steroids GroupControl GroupTotal
Caucasian4654100
Region of Enrollment
Region of Enrollment(participants)Steroids GroupControl GroupTotal
Greece4654100
Body Mass Index
Body Mass Index(kg/m^2)Steroids GroupControl GroupTotal
Mean27.5 ± 8.827.2 ± 5.927.4 ± 7.3
Hypertension
Hypertension(Participants)Steroids GroupControl GroupTotal
Count of participants313162
Coronary Artery Disease
Coronary Artery Disease(Participants)Steroids GroupControl GroupTotal
Count of participants141529
Diabetes
Diabetes(Participants)Steroids GroupControl GroupTotal
Count of participants141731

13 further baseline measures are reported on the registry.

08

Study locations

2 sites
  • Department of Intensive Care Medicine, Evaggelismos Hospital
    Athens, Attica GR-10675, Greece
  • Larisa University General Hospital
    Larisa, Thessaly GR-41110, Greece
09

References and documents

Publications

  • Girotra S, Nallamothu BK, Spertus JA, Li Y, Krumholz HM, Chan PS; American Heart Association Get with the Guidelines-Resuscitation Investigators. Trends in survival after in-hospital cardiac arrest. N Engl J Med. 2012 Nov 15;367(20):1912-20. doi: 10.1056/NEJMoa1109148. PubMed 23150959 ↗
  • Al-Alwan A, Ehlenbach WJ, Menon PR, Young MP, Stapleton RD. Cardiopulmonary resuscitation among mechanically ventilated patients. Intensive Care Med. 2014 Apr;40(4):556-63. doi: 10.1007/s00134-014-3247-2. Epub 2014 Feb 26. PubMed 24570267 ↗
  • 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. PubMed 19139319 ↗
  • 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. PubMed 23860985 ↗
  • Adrie C, Adib-Conquy M, Laurent I, Monchi M, Vinsonneau C, Fitting C, Fraisse F, Dinh-Xuan AT, Carli P, Spaulding C, Dhainaut JF, Cavaillon JM. Successful cardiopulmonary resuscitation after cardiac arrest as a "sepsis-like" syndrome. Circulation. 2002 Jul 30;106(5):562-8. doi: 10.1161/01.cir.0000023891.80661.ad. PubMed 12147537 ↗
  • 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. PubMed 15166838 ↗
  • Pene F, Hyvernat H, Mallet V, Cariou A, Carli P, Spaulding C, Dugue MA, Mira JP. Prognostic value of relative adrenal insufficiency after out-of-hospital cardiac arrest. Intensive Care Med. 2005 May;31(5):627-33. doi: 10.1007/s00134-005-2603-7. Epub 2005 Apr 19. PubMed 15838680 ↗
  • Kim JJ, Lim YS, Shin JH, Yang HJ, Kim JK, Hyun SY, Rhoo I, Hwang SY, Lee G. Relative adrenal insufficiency after cardiac arrest: impact on postresuscitation disease outcome. Am J Emerg Med. 2006 Oct;24(6):684-8. doi: 10.1016/j.ajem.2006.02.017. PubMed 16984836 ↗
  • 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. PubMed 15257083 ↗
  • Tsai MS, Huang CH, Chang WT, Chen WJ, Hsu CY, Hsieh CC, Yang CW, Chiang WC, Ma MH, Chen SC. The effect of hydrocortisone on the outcome of out-of-hospital cardiac arrest patients: a pilot study. Am J Emerg Med. 2007 Mar;25(3):318-25. doi: 10.1016/j.ajem.2006.12.007. PubMed 17349907 ↗
  • Schultz CH, Rivers EP, Feldkamp CS, Goad EG, Smithline HA, Martin GB, Fath JJ, Wortsman J, Nowak RM. A characterization of hypothalamic-pituitary-adrenal axis function during and after human cardiac arrest. Crit Care Med. 1993 Sep;21(9):1339-47. doi: 10.1097/00003246-199309000-00018. PubMed 8396524 ↗
  • Vaahersalo J, Skrifvars MB, Pulkki K, Stridsberg M, Rosjo H, Hovilehto S, Tiainen M, Varpula T, Pettila V, Ruokonen E; FINNRESUSCI Laboratory Study Group. Admission interleukin-6 is associated with post resuscitation organ dysfunction and predicts long-term neurological outcome after out-of-hospital ventricular fibrillation. Resuscitation. 2014 Nov;85(11):1573-9. doi: 10.1016/j.resuscitation.2014.08.036. Epub 2014 Sep 17. PubMed 25238742 ↗
  • Bro-Jeppesen J, Kjaergaard J, Stammet P, Wise MP, Hovdenes J, Aneman A, Horn J, Devaux Y, Erlinge D, Gasche Y, Wanscher M, Cronberg T, Friberg H, Wetterslev J, Pellis T, Kuiper M, Nielsen N, Hassager C; TTM-Trial Investigators. Predictive value of interleukin-6 in post-cardiac arrest patients treated with targeted temperature management at 33 degrees C or 36 degrees C. Resuscitation. 2016 Jan;98:1-8. doi: 10.1016/j.resuscitation.2015.10.009. Epub 2015 Oct 23. PubMed 26525271 ↗
  • Peberdy MA, Andersen LW, Abbate A, Thacker LR, Gaieski D, Abella BS, Grossestreuer AV, Rittenberger JC, Clore J, Ornato J, Cocchi MN, Callaway C, Donnino M; National Post Arrest Research Consortium (NPARC) Investigators. Inflammatory markers following resuscitation from out-of-hospital cardiac arrest-A prospective multicenter observational study. Resuscitation. 2016 Jun;103:117-124. doi: 10.1016/j.resuscitation.2016.01.006. Epub 2016 Jan 27. PubMed 26826561 ↗
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Study documents

  • Protocol, analysis plan and consent form · May 23, 2016

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 23, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02790788
Lead sponsor
University of Athens
Collaborators
University of Thessaly
Responsible party
Spyros D. Mentzelopoulos (MD, PhD, DEAA, EDIC, Associate Professor of Intensive Care Medicine, University of Athens) — Principal investigator
First posted
Jun 6, 2016
Start date
Nov 4, 2016
Primary completion
May 22, 2018
Completion
Aug 11, 2018
Results posted
Nov 18, 2019
Last update
Nov 23, 2021

Study contacts

Spyros D. Mentzelopoulos, MD, PhD
principal investigator · University of Athens
Spyros G. Zakynthinos, MD, PhD
study chair · University of Athens

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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