Effect of Combined Vitamin C, Stress-dose Steroids, and Thiamine on Cerebral Autoregulation and Functional Outcomes of Patients with Septic Shock
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Cerebral autoregulation
研究概览
简要总结
This study has been approved as a nested substudy of a multicenter trial (CORVICTES, Clinicaltrials.gov Identifier: NCT03592693). The current, randomized, placebo-controlled study will compare steroids/vitamin C versus placebo/placebo in septic shock, with respect to cerebral autoregulation, biomarkers, and functional outcome. The following hypotheses will be tested: The steroids/vitamin C/thiamine intervention may result in attenuation of the septic shock-associated impairment in cerebral autoregulation; and 2) The increased frequency of intact cerebral autoregulation in the intervention group may result in more neurologic failure free days and ventilator free days during a 60-day follow-up; improved survival to hospital discharge with good functional outcome; and better patient-reported health-related outcomes at 90-day follow-up.
详细描述
BACKGROUND AND RATIONALE Septic Encephalopathy is a serious complication of sepsis / septic shock. In postmortem, human brain samples, two forms of neuraxonal injury have been described, namely, scattered ischemic lesions and diffuse injury. Prior evidence suggests that cerebral autoregulation is impaired in patients with septic shock, and this may render the central nervous system more vulnerable to direct ischemic damage, especially during episodes of hypotension. Near-infrared spectroscopy (NIRS) constitutes an established method of noninvasive assessment of cerebral autoregulation and provides the capability of semiquantitative assessment of regional cerebral blood flow.
In the context of a multicenter randomized clinical trial (RCT) evaluating the effect of steroids and antioxidants on the outcome of septic shock, we aim to assess cerebral autoregulation and frontal cortex perfusion using NIRS in patients who will be enrolled in the 25-bed intensive care unit (ICU) of Evaggelismos Hospital, Athens, Greece.
The rationale of the main study is based on the following facts: A large body of experimental data has demonstrated that both corticosteroids and intravenous vitamin C reduce activation of nuclear factor kappa beta (NFƘB), thereby attenuating the release of pro-inflammatory mediators. This may result in reduced endothelial permeability and improved macrocirculatory flow, and augmentation of the release of endogenous catecholamines and enhanced vasopressor responsiveness. Furthermore, a combined attenuation of the systemic inflammatory response, reduced vascular leakage, and improved macrocirculatory flow may partly contribute to the preservation of cerebral autoregulation and effective, regional brain perfusion. In addition, recent evidence suggests that thiamine may be neuroprotective in severe shock states.
Regarding the rationale and hypotheses of the current substudy: Recent, observational data suggest that impaired cerebral autoregulation is independently associated with 3-month mortality in patients with septic shock. Therefore, the current project aims to test the following hypotheses: 1) The steroids/vitamin C/thiamine intervention may result in attenuation of the septic shock-associated impairment in cerebral autoregulation; and 2) The increased frequency of intact cerebral autoregulation in the intervention group may result in more neurologic failure free days and ventilator free days during a 60-day follow-up; improved survival to hospital discharge with good functional outcome; and better patient-reported health-related outcomes at 90-day follow-up.
METHODS
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)
盲法说明
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
- •Diagnosis of septic shock within 12 hours of admission to the intensive care unit (ICU).
排除标准
- •Age < 18 years
- •Pregnancy
- •Patients with a fatal underlying disease who are unlikely to survive to hospital discharge
- •Patients with acquired immunodeficiency and a CD4 count of < 50 / μL
- •Patients with known glucose-6 phosphate dehydrogenase (G-6PD) deficiency.
- •Patients with sepsis/septic shock transferred from another hospital
- •Patients with features of sepsis/septic shock > 12 hours
- •Patients who require treatment with corticosteroids for an indication other than sepsis
- •Patients with any history of an allergic reaction
研究组 & 干预措施
Control group
"Placebo plus placebo:" Patients with septic shock treated with placebo (corresponding to Vitamin C) and placebo (corresponding to hydrocortisone) for 4 days after randomization.
干预措施: isotonic sodium chloride solution placebo plus isotonic sodium chloride solution placebo (Drug)
Steroids/Vitamin C group
"Combined Vitamin C and Stress-Dose Hydrocortisone": Patients with septic shock treated with 1500 mg Vitamin C every 6 hours for 4 days after randomization, and stress-dose hydrocortisone for 4 days (250 mg on day 1; and 200 mg on days 2, 3, and 4) after randomization.
干预措施: Stress-dose Hydrocortisone plus Vitamin C (Drug)
结局指标
主要结局
Cerebral autoregulation
时间窗: 24-78 hours after randomization
Cerebral autoregulation while increasing MAP from a minimum of 65-75 mmHg to a maximum of 90-100 mmHg by changing the vasopressor infusion rate.
Cerebral blood flow
时间窗: 24-78 hours after randomization
Cerebral blood flow at an MAP of 65-75 mmHg and an MAP of 90-100 mmHg
次要结局
- Biomarkers(24-72 hours after randomization)
- Neurologic failure free days(Days 1-60 after randomization)
- Ventilator-free days(Days 1-60 after randomization)
- Favorable, Inhospital, Neurological Outcome(Days 1-60 after randomization)
- Patient-reported health-related quality of life: SF-36(90 days after randomization)
研究者
Spyros D. Mentzelopoulos
Associate Professor of Intensive Care Medicine
University of Athens