Combination Therapy of Vitamin C and Thiamine for Septic Shock: Multi-center, Double-blinded, Randomized, Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 116
- 试验地点
- 6
- 主要终点
- Delta Sequential Organ Failure Assessment (SOFA) score
研究概览
简要总结
The aim of this study is to evaluate the efficacy of early metabolic resuscitation with combination therapy using vitamin C and thiamine in improving organ function and survival in patients with septic shock.
详细描述
Sepsis is a complex disease involving life-threatening organ dysfunction caused by a dysregulated host response to infection and is still associated with unacceptably high mortality. Sepsis management should be undertaken as a medical emergency and focused on timely intervention, including early identification and treatment of infection through appropriate antimicrobial therapy and source control when applicable as well as reversing hemodynamic instability through fluid resuscitation and vasopressor use if necessary. Despite these supportive therapies, morbidity and mortality have remained high, suggesting the need for adjuvant therapies for inflammatory and oxidative stress in patients with sepsis; however, no agents have been proven to definitely improve survival.
Vitamin C plays a role in mediating inflammation through antioxidant activities and is also important as a cofactor/co-substrate for the synthesis of endogenous adrenaline, cortisol, and vasopressin. Recently, several clinical trials have reported the positive effects of vitamin C on outcomes in sepsis or septic shock. During sepsis, vitamin C prevents neutrophil-induced lipid oxidation and protects against the loss of the endothelial barrier. Early intravenous supplementation is therefore needed to limit loss of microcirculation and oxidation of lipids. Thiamine is also a key cofactor for glucose metabolism, the generation of ATP (adenosine triphosphate), and the production of NADPH. Considering acute consumption in the hypermetabolic state, thiamine supplementation might be a reasonable therapeutic adjunct for patients with sepsis and was added to reduce the risk of renal oxalate crystallization. These findings led to a recent before-and-after study showing that treatment of sepsis with a combination of vitamin C, hydrocortisone, and thiamine prevented organ dysfunction and reduced the mortality rate.
The aim of this study is to evaluate the efficacy of early metabolic resuscitation with combination therapy using vitamin C and thiamine in improving organ function and survival in patients with septic shock.
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
- 19 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (> 18 years)
- •Septic shock: sepsis with persisting hypotension requiring vasopressors to maintain a mean arterial pressure ≥65 mm Hg and a serum lactate level >2 mmol/L despite adequate volume resuscitation. Sepsis is defined as clinically suspected or confirmed infection with acute organ failure identified as an acute change in total SOFA score with 2 points or more.
排除标准
- •Transferred patients from other hospitals after application of vasopressors or mechanical ventilation
- •Patients who signed a "Do not attempt resuscitation" order or who had set limitations on invasive care
- •Patients who have a terminal, unresponsive illness and survival discharge is not expected (metastatic terminal cancer, etc.)
- •Patients who experienced cardiac arrest before enrollment or when death is anticipated within 24 hours despite maximal treatment
- •Patients who take more than 1g of Vitamin C per day before enrollment or who take supplemental thiamine
- •Pregnant woman
- •Known Glucose-6-phosphate dehydrogenase deficiency
- •Patients with a history of hypersensitivity to vitamin C or thiamine
- •Known Mediterranean anemia
- •Known hyperoxaluria
- •Known cystinuria
- •Acute gout attack
- •Known oxalate renal stone
- •Patients who meet the inclusion criteria 24 hours after emergency department arrival or when enrollment is delayed more than 24 hours after diagnosis of septic shock
- •Inability or refusal of a subject or legal surrogate to give informed consent
研究组 & 干预措施
Treatment
Combination therapy of vitamin C and thiamine for 2 days.
干预措施: Combination therapy of vitamin C and thiamine (Drug)
Control
Normal Saline Solution
干预措施: Normal saline solution (Drug)
结局指标
主要结局
Delta Sequential Organ Failure Assessment (SOFA) score
时间窗: Enrollment to 72 hours
72-hour change in SOFA score, which reflected recovery from organ failure (delta SOFA = SOFA at enrollment - SOFA after 72 hours)
次要结局
- 28-day mortality(Day 28)
- 7-day mortality (early death)(Day 7)
- 90-day mortality(Day 90)
- Time to death(Enrollment to Day 28)
- In-hospital death(Up to 12 weeks)
- Intensive care unit death (ICU) death(Up to 12 weeks)
- Time to Shock reversal(Enrollment to Day 14)
- Vasopressor free days(Enrollment to Day 14)
- New use of renal replacement therapy (RRT)(Up to 12 weeks)
- Renal replacement therapy (RRT) free days(Enrollment to Day 14)
- New onset or aggravation of acute kidney injury (AKI)(Enrollment to Day 14)
- Length of ICU stay(Up to 12 weeks)
- ICU free day(Enrollment to Day 14)
- Length of hospital stay(Up to 12 weeks)
- Ventilator free days(Enrollment to Day 14)
- Ventilator duration(Up to 12 weeks)
研究者
Tae Gun Shin
Associate professor
Samsung Medical Center