Physiologic Effects of Stress Dose Corticosteroids in the Management of Inhospital Cardiac Arrest - CORTICA
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring (as Feasible).
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Methylprednisolone; hydrocortisone (Drug)
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).
干预措施: Saline Placebo (Drug)
结局指标
主要结局
Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring (as Feasible).
时间窗: 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.
Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port.
时间窗: 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.
Early Postresuscitation Central Venous Oxygen Saturation (%) Measured in Blood Samples Obtained Through a Central Venous Catheter Port (as Feasible).
时间窗: 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.
Early Postresuscitation Arterial Blood Pressure (mmHg) Measured Through Institution of Invasive Intra-arterial Pressure Monitoring.
时间窗: 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.
次要结局
- Eccentricity Index by Echocardiography.(Time points of measurement: Within the first 12 hours and at 72 hours postresuscitation.)
- Survival to Hospital Discharge With Favorable Functional Outcome.(Up to 180 days postrandomization.)
- Steroid-associated Complications.(Up to 180 days postrandomization.)
- Left and Right Ventricular Diastolic Area (cm^2) by Echocardiography.(Time points of measurement: Within the first 12 hours and at 72 hours postresuscitation.)
- Left and Right Ventricular Ejection Fraction (%) by Echocardiography.(Time points of measurement: Within the first 12 hours and at 72 hours postresuscitation.)
- Early Postresuscitation Cardiac Output (L/Min) Measured by Either Pulse Index Continuous Cardiac Output (PiCCO) or a Continuous Cardiac Output (CCO) Thermodilution Pulmonary Artery Catheter.(Time points of measurement: 72 hours after ROSC.)
- Cerebral Blood Flow Index by Near Infrared Spectroscopy With Indocyanine Green.(Time points of measurement: 4 and 72 hours postresuscitation.)
- Organ Failure-free Days.(Days 1 to 60 postrandomization.)
- Core Body Temperature in Degrees Celcius.(Time points of measurement: Hourly from intensive care admission to 48 hours postresuscitation.)
- Early Postresuscitation Inflammatory Response as Assessed by Serum Cytokine Levels (pg/mL).(Time points of measurement: 4, 24, 48, and 72 hours postresuscitation.)
研究者
Spyros D. Mentzelopoulos
MD, PhD, DEAA, EDIC, Associate Professor of Intensive Care Medicine
University of Athens