Impact of Vitamin C on Biomarkers of Neurologic Injury in Patients With Return of Spontaneous Circulation After Out-of-Hospital Cardiac Arrest
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Biomarkers of neurological injury
研究概览
简要总结
Out-of-hospital cardiac arrest (OHCA) is one of the leading cause of death in the world. In Slovenia approximately 25% of resuscitated patients survives to discharge from hospitals, usually with poorer functional status.
One of key pathophysiological process responsible for poorer functional status is global hypoxic-ischemic injury, which is two-stage. Primary stage occurs immediately after cardiac arrest due to cessation of blood flow. With return of spontaneous circulation a secondary injury occurs, of which the leading process is an imbalance between oxygen delivery and consumption. Reperfusion exposes ischemic tissue to oxygen, resulting in the formation of large amounts of highly reactive oxygen species (ROS) within minutes. ROS lead to oxidative stress, which causes extensive damage to cell structures and leads to cell death. Consequently, necrosis and apoptosis are responsible for organ dysfunction and functional outcome of these patients.
Such injury of neural tissue causes brain damage, which is ultimately responsible for poor neurological and thus functional outcome of OHCA survivors. The extent of brain damage can be determined in several ways: clinically by assessing quantitative and qualitative consciousness and the presence of involuntary movements in an unconscious patient, by assessing activity on electroencephalographic record, by imaging of the brain with computed tomography and magnetic resonance imaging, as well as by assessing levels of biological markers of brain injury. Of the latter, the S-100b protein and neuron-specific enolase have been shown to be suitable for such assessment.
Oxidative stress is counteracted by the body with endogenous antioxidants that balance excess free radicals and stabilize cellular function. Vitamin C (ascorbic acid) is the body's main antioxidant and is primarily consumed during oxidative stress. Large amounts of ROS rapidly depletes the body's vitamin C stores.
Humans cannot synthesise vitamin C and enteral uptake of vitamin C is limited by transporter saturation. On the other hand, parenteral (venous) dosing of vitamin C can achieve concentrations of vitamin C above physiological and thus produce a stronger antioxidant effect. The beneficial effect of parenteral dosing of vitamin C has been establish in several preclinical and clinical studies in patients with ischemic stroke and cardiac arrest.
The investigators hypothesize that there is a similarly beneficial effect of vitamin C in survivors of OHCA.
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
- Triple (Participant, Care Provider, 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
- •comatose survivors of out-of-hospital arrest
排除标准
- •patients with trauma, asphyxia, drowning or electrocution as a cause of cardiac arrest
- •history of oxalate nephropathy or nephrolithiasis, glucose-6-phosphate dehydrogenase deficiency, and hemochromatosis
- •pregnancy
研究组 & 干预措施
Vitamin C
Group of patients that will receive vitamin C (ascorbic acid 1,5 g mixed with 0,9 % solution of sodium chloride 100 ml every 12 hours for 4 days intravenously).
干预措施: Vitamin C (Drug)
Placebo
Group of patients that will receive placebo (0,9 % solution of sodium chloride 100 ml every 12 hours for 4 days intravenously).
干预措施: Placebo (Drug)
结局指标
主要结局
Biomarkers of neurological injury
时间窗: 5th day
Serum levels of protein S-100b and neuron-specific enolase.
次要结局
- Electroencephalography (EEG)(3rd-10th day)
- Evaluation of GCS(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Evaluation of heart failure(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Serum Brain natriuretic peptide(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Mechanical ventilation(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Brain imaging (CT and MRI)(3rd-10th day)
- Evaluation of pupils(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Evaluation of involuntary movements(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Evaluation of FOUR(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Cerebral Performance Category(from admission till discharge from ICU or death (whatever comes first))
- Left ventricular ejection fraction(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Arrhythmias(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Serum troponin level(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Vasopressor and/or inotrope need(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Kidney failure(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Serum creatinine levels(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Serum procalcitonin levels(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Serum urea levels(from admission until 14 days or till discharge from ICU or death (whatever comes first))
- Serum C-reactive protein levels(from admission until 14 days or till discharge from ICU or death (whatever comes first))