Study Results
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Recruitment Status
COMPLETED
Clinical Phase
PHASE1/PHASE2
Total Enrollment
100 participants
Study Classification
INTERVENTIONAL
Study Start Date
2016-11-04
Study Completion Date
2018-08-11
Brief Summary
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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.
Detailed Description
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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.
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.
Conditions
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Inhospital Cardiac Arrest
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
QUADRUPLE
Participants
Caregivers
Investigators
Outcome Assessors
Study Groups
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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.
Group Type
EXPERIMENTAL
Methylprednisolone; hydrocortisone
Intervention Type
DRUG
Methylprednisolone 40 mg during resuscitation and stress-dose hydrocortisone for postresuscitation shock
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).
Group Type
PLACEBO_COMPARATOR
Saline Placebo
Intervention Type
DRUG
Saline placebo during resuscitation and during the postresuscitation phase.
Interventions
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Methylprednisolone; hydrocortisone
Methylprednisolone 40 mg during resuscitation and stress-dose hydrocortisone for postresuscitation shock
Intervention Type
DRUG
Saline Placebo
Saline placebo during resuscitation and during the postresuscitation phase.
Intervention Type
DRUG
Other Intervention Names
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Solumedrol; Solucortef
Isotonic sodium chloride placebo
Eligibility Criteria
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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.
* Ventricular fibrillation/pulseless tachycardia not responsive to three direct current countershocks, or
* Asystole, or
* Pulseless electrical activity.
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.
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.
* 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.
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.
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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University of Thessaly
OTHER
Sponsor Role
collaborator
University of Athens
OTHER
Sponsor Role
lead
Responsible Party
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Spyros D. Mentzelopoulos
MD, PhD, DEAA, EDIC, Associate Professor of Intensive Care Medicine
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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Spyros D. Mentzelopoulos, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Athens
Spyros G. Zakynthinos, MD, PhD
Role: STUDY_CHAIR
University of Athens
Locations
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Department of Intensive Care Medicine, Evaggelismos Hospital
Athens, Attica, Greece
Site Status
Larisa University General Hospital
Larissa, Thessaly, Greece
Site Status
Countries
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Greece
References
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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.
Reference Type
BACKGROUND
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.
Reference Type
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.
Reference Type
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.
Reference Type
BACKGROUND
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.
Reference Type
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013 Feb;39(2):165-228. doi: 10.1007/s00134-012-2769-8. Epub 2013 Jan 30.
Reference Type
BACKGROUND
Soar J, Nolan JP, Bottiger BW, Perkins GD, Lott C, Carli P, Pellis T, Sandroni C, Skrifvars MB, Smith GB, Sunde K, Deakin CD; Adult advanced life support section Collaborators. European Resuscitation Council Guidelines for Resuscitation 2015: Section 3. Adult advanced life support. Resuscitation. 2015 Oct;95:100-47. doi: 10.1016/j.resuscitation.2015.07.016. No abstract available.
Reference Type
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.
Reference Type
BACKGROUND
Fergusson D, Aaron SD, Guyatt G, Hebert P. Post-randomisation exclusions: the intention to treat principle and excluding patients from analysis. BMJ. 2002 Sep 21;325(7365):652-4. doi: 10.1136/bmj.325.7365.652. No abstract available.
Reference Type
BACKGROUND
REGULATION (EU) No 536/2014 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC. Official Journal of the European Union 2014; L158/1-L158/76.
Reference Type
BACKGROUND
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. doi: 10.1001/jama.2013.281053. No abstract available.
Reference Type
BACKGROUND
Cummins RO, Chamberlain D, Hazinski MF, Nadkarni V, Kloeck W, Kramer E, Becker L, Robertson C, Koster R, Zaritsky A, Bossaert L, Ornato JP, Callanan V, Allen M, Steen P, Connolly B, Sanders A, Idris A, Cobbe S. Recommended guidelines for reviewing, reporting, and conducting research on in-hospital resuscitation: the in-hospital 'Utstein style'. American Heart Association. Circulation. 1997 Apr 15;95(8):2213-39. doi: 10.1161/01.cir.95.8.2213. No abstract available.
Reference Type
BACKGROUND
Boushel R, Langberg H, Olesen J, Nowak M, Simonsen L, Bulow J, Kjaer M. Regional blood flow during exercise in humans measured by near-infrared spectroscopy and indocyanine green. J Appl Physiol (1985). 2000 Nov;89(5):1868-78. doi: 10.1152/jappl.2000.89.5.1868.
Reference Type
BACKGROUND
Mentzelopoulos SD, Pappa E, Malachias S, Vrettou CS, Giannopoulos A, Karlis G, Adamos G, Pantazopoulos I, Megalou A, Louvaris Z, Karavana V, Aggelopoulos E, Agaliotis G, Papadaki M, Baladima A, Lasithiotaki I, Lagiou F, Temperikidis P, Louka A, Asimakos A, Kougias M, Makris D, Zakynthinos E, Xintara M, Papadonta ME, Koutsothymiou A, Zakynthinos SG, Ischaki E. Physiologic effects of stress dose corticosteroids in in-hospital cardiac arrest (CORTICA): A randomized clinical trial. Resusc Plus. 2022 May 26;10:100252. doi: 10.1016/j.resplu.2022.100252. eCollection 2022 Jun.
Reference Type
DERIVED
Provided Documents
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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CORTICA-15519/23/5/16
Identifier Type: -
Identifier Source: org_study_id