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Physiologic Effects of Steroids in Cardiac Arrest (CORTICA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02790788
Recruitment Status : Completed
First Posted : June 6, 2016
Results First Posted : November 18, 2019
Last Update Posted : November 18, 2019
Sponsor:
Collaborator:
University of Thessaly
Information provided by (Responsible Party):
Spyros D. Mentzelopoulos, University of Athens

Brief Summary:
Early stress-dose steroids are of uncertain efficacy in cardiac arrest. The current authors plan to conduct a 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.

Condition or disease Intervention/treatment Phase
Inhospital Cardiac Arrest Drug: Methylprednisolone; hydrocortisone Drug: Saline Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Physiologic Effects of Stress Dose Corticosteroids in the Management of Inhospital Cardiac Arrest - CORTICA
Actual Study Start Date : November 4, 2016
Actual Primary Completion Date : May 22, 2018
Actual Study Completion Date : August 11, 2018


Arm Intervention/treatment
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
Methylprednisolone 40 mg during resuscitation and stress-dose hydrocortisone for postresuscitation shock
Other Name: Solumedrol; Solucortef

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
Saline placebo during resuscitation and during the postresuscitation phase.
Other Name: Isotonic sodium chloride placebo




Primary Outcome Measures :
  1. Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring (as Feasible). [ Time Frame: Time point of measurement: 20 min after the return of spontaneous circulation (ROSC). ]
    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).

  2. Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port (as Feasible). [ Time Frame: Time points of measurement: 20 min after ROSC. ]
    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.

  3. Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring (as Feasible). [ Time Frame: Time points of measurement: 4 hours after ROSC. ]
    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.

  4. Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port (as Feasible). [ Time Frame: Time points of measurement: 4 hours after ROSC. ]
    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.

  5. Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring. [ Time Frame: Time points of measurement: 24 hours after ROSC. ]
    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.

  6. Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port. [ Time Frame: Time points of measurement: 24 hours after ROSC. ]
    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.

  7. Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring. [ Time Frame: Time points of measurement: 48 hours after ROSC. ]
    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.

  8. Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port. [ Time Frame: Time points of measurement: 48 hours after ROSC. ]
    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.

  9. Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring. [ Time Frame: Time points of measurement: 72 hours after ROSC. ]
    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.

  10. Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port. [ Time Frame: Time points of measurement: 72 hours after ROSC. ]
    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.


Secondary Outcome Measures :
  1. Left and Right Ventricular Diastolic Area (cm^2) by Echocardiography. [ Time Frame: Time points of measurement: Within the first 12 hours and at 72 hours postresuscitation. ]
    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.

  2. Left and Right Ventricular Ejection Fraction (%) by Echocardiography. [ Time Frame: Time points of measurement: Within the first 12 hours and at 72 hours postresuscitation. ]
    Results are provided on left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) within 12 hours and 72 hours after ROSC.

  3. Eccentricity Index by Echocardiography. [ Time Frame: Time points of measurement: Within the first 12 hours and at 72 hours postresuscitation. ]
    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.

  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. [ Time Frame: Time points of measurement: 4 hours after ROSC. ]
    RESULTS ARE PROVIDED FOR CARDIAC OUTPUT (CO) AT 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. [ Time Frame: Time points of measurement: 24 hours after ROSC. ]
    Results are provided for CO at 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. [ Time Frame: Time points of measurement: 48 hours after ROSC. ]
    Results are provided for CO at 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. [ Time Frame: Time points of measurement: 72 hours after ROSC. ]
    Results are provided for CO at 72 hours after ROSC.

  8. Core Body Temperature in Degrees Celcius. [ Time Frame: Time points of measurement: Hourly from intensive care admission to 48 hours postresuscitation. ]
    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.

  9. Cerebral Blood Flow Index by Near Infrared Spectroscopy With Indocyanine Green. [ Time Frame: Time points of measurement: 4 and 72 hours postresuscitation. ]
    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

  10. Organ Failure-free Days. [ Time Frame: Days 1 to 60 postrandomization. ]
    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.

  11. Early Postresuscitation Inflammatory Response as Assessed by Serum Cytokine Levels (pg/mL). [ Time Frame: Time points of measurement: 4, 24, 48, and 72 hours postresuscitation. ]
    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.

  12. Survival to Hospital Discharge With Favorable Functional Outcome. [ Time Frame: Up to 180 days postrandomization. ]
    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.

  13. Steroid-associated Complications. [ Time Frame: Up to 180 days postrandomization. ]
    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).



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

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:

  • 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.


Information from the National Library of Medicine

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

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02790788


Locations
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Greece
Department of Intensive Care Medicine, Evaggelismos Hospital
Athens, Attica, Greece, GR-10675
Larisa University General Hospital
Larisa, Thessaly, Greece, GR-41110
Sponsors and Collaborators
University of Athens
University of Thessaly
Investigators
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Principal Investigator: Spyros D. Mentzelopoulos, MD, PhD University of Athens
Study Chair: Spyros G. Zakynthinos, MD, PhD University of Athens
  Study Documents (Full-Text)

Documents provided by Spyros D. Mentzelopoulos, University of Athens:
Publications:
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.

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Responsible Party: Spyros D. Mentzelopoulos, MD, PhD, DEAA, EDIC, Associate Professor of Intensive Care Medicine, University of Athens
ClinicalTrials.gov Identifier: NCT02790788    
Other Study ID Numbers: CORTICA-15519/23/5/16
First Posted: June 6, 2016    Key Record Dates
Results First Posted: November 18, 2019
Last Update Posted: November 18, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Heart Arrest
Heart Diseases
Cardiovascular Diseases
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Hydrocortisone
Hydrocortisone hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents