Ascorbic Ccid, Hydrocortisone, and Thiamine in Sepsis and Septic Shock - A Randomized, Double-Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 205
- 试验地点
- 13
- 主要终点
- Sequential Organ Failure Assessment (SOFA) Score at Baseline and 72 Hours
研究概览
简要总结
In this study, we aim to determine whether the combination of Ascorbic Acid (Vitamin C), Thiamine (Vitamin B1), and Corticosteroids improves the trajectory of organ failure and reduces mortality in patients with sepsis and septic shock as compared to placebo.
详细描述
Sepsis and Septic Shock are common and highly morbid clinical conditions without any specific therapy aside from antibiotics. A recent quasi-experimental study (Marik et. al., PMID 27940189) demonstrated a remarkable benefit when the combination of Ascorbic Acid (Vitamin C), Corticosteroids, and Thiamine (Vitamin B1) were given to patients with sepsis. In particular, patients who received this combination of medications required a shorter amount of time on vasopressors, suffered less organ failure, and had improved mortality. Vitamin C has long been suggested for treatment of patients with severe infection as it exerts significant anti-oxidant effects and reduces endothelial permeability. Corticosteroids, a mainstay of therapy for refractory shock in sepsis, have also been shown to enhance the beneficial cellular effects of vitamin C. Finally, thiamine has been shown to be an effective mitochondrial resuscitator in sepsis, especially for the ~30% of septic shock patients who present with thiamine deficiency (Donnino et. al, PMID 26771781).
In this study, we aim to reproduce the findings of Marik et. al. using a more rigorous study design (i.e. a blinded, randomized clinical trial) and focus on the important clinical outcomes of organ failure and death.
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 patient (age ≥ 18 years)
- •Suspected (cultures drawn and antibiotic given) or confirmed (via culture results) infection
- •Receiving vasopressor (norepinephrine, phenylephrine, epinephrine, dopamine, angiotensin II or vasopressin)
排除标准
- •Member of a protected population (pregnant, prisoner)
- •Known kidney stones within the past 1 year (except for asymptomatic, incidentally noted stones on imaging)
- •End stage renal disease (ESRD) requiring dialysis
- •Known Glucose-6-Phosphate Dehydrogenase deficiency
- •Known Hemachromatosis
- •Comfort Measures Only status
- •Anticipated death within 24-hours despite maximal therapy (as determined by the enrolling physician)
- •Receiving supplemental thiamine in a dose greater than that contained in a multivitamin
- •Clinical indication for steroids (e.g. chronic use) as determined by the clinical team providing this drug
- •Clinical indication for thiamine as determined by the clinical team providing this drug
- •Clinical indication for ascorbic acid as determined by the clinical team providing this drug
- •Known allergy to vitamin C, hydrocortisone, or thiamine
研究组 & 干预措施
Vitamin C, Vitamin B1, Corticosteroids
The combination of vitamin C, vitamin B1, hydrocortisone :
- Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
- Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
- Hydrocortisone 50mg every 6 hours x 4-days
干预措施: vitamin C, vitamin B1, hydrocortisone (Drug)
Placebo
Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components
干预措施: Normal saline (Drug)
结局指标
主要结局
Sequential Organ Failure Assessment (SOFA) Score at Baseline and 72 Hours
时间窗: Enrollment to 72-hours
Sequential Organ Failure Assessment (SOFA) Score at Baseline and 72 Hours. The SOFA score ranges from a minimum of 0 to a maximum of 24, with higher scores meaning worse outcomes.
次要结局
- 30-day Mortality(Enrollment until 30-days after enrollment)
- Renal Failure(Enrollment until 7-days or discharge from the ICU)
研究者
Michael Donnino
Associate Professor of Emergency Medicine
Beth Israel Deaconess Medical Center