Evaluation of Hydrocortisone, Vitamin C and Thiamine for the Treatment of Septic Shock
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 106
- 试验地点
- 1
- 主要终点
- Hospital Mortality at 60 days
研究概览
简要总结
Despite recent medical advances, sepsis and septic shock remain a major cause of death. Sepsis is a syndrome with a wide array of physiologic, pathologic, and biochemical abnormalities.
Several studies have shown vitamin C have decreased the circulating pro-inflammatory cytokines and oxidative stress.Thiamine had favorable effects on pro-inflammatory cytokines, oxidative stress and cellular hypoxia.The use of hydrocortisone in combination with vitamin C will increase the transport of vitamin C into the cells; since the pro inflammatory cytokines have shown to decrease the expression of the sodium-vitamin C transporter-2 (SVCT2) while glucocorticoids increase the SVCT2 expression.
A recent small retrospective study , showed a significant decrease in mortality when patients with severe sepsis and septic shock are treated with a combination of Hydrocortisone, Vitamin C, and Thiamine. Conducting a similar study with a prospective randomized design will give clinicians all over the world more answers and will help clinicians to provide better care to millions of patients using highly safe therapeutic regimen.
The objective of the current study is to explore the clinical benefits of using a combination of hydrocortisone, vitamin C, and thiamine (triple therapy) for the management of septic shock. To achieve this objective, we will compare two alternative treatment strategies, either triple therapy or usual care in patients with septic shock.
First aim: To assess the effectiveness of the triple therapy for septic shock
Second aim: To assess the safety of triple therapy
详细描述
Critically ill patients have low plasma levels of vitamin C. Additionally, ascorbic acid levels were inversely correlated with multi-organ dysfunction. Several studies have shown the benefit of using Vitamin C for treatment of critically ill patients; these benefits included dose dependent decrease in the SOFA score, lower vasopressor doses and duration, and lower fluid resuscitation requirements. Additionally, Intravenous Vitamin C has been shown to be safe and tolerable.
A small study demonstrated that septic shock is associated with thiamine deficiency. Additionally, a randomized controlled trial has shown that intravenous thiamine has decreased lactate levels and mortality in a subgroup of patients with thiamine deficiency. However, this benefit was not observed in the entire population of the study.
A recent study examined the effect of early treatment of patients with severe sepsis and septic shock with a combination of hydrocortisone, vitamin C, and thiamine and demonstrated a significant reduction in mortality as well as preventing organ failure progression. In this study, It has been suggested that this combination of the three agents work synergistically. The use of hydrocortisone in combination with vitamin C will increase the transport of vitamin C into the cells; since the pro inflammatory cytokines have shown to decrease the expression of the sodium-vitamin C transporter-2 (SVCT2) while glucocorticoids increase the SVCT2 expression. In an in vitro study a combination of hydrocortisone and vitamin C preserved the endothelial integrity of the lung vascular endothelial cells which was exposed to endotoxins. On the other hand either agent alone was not effective in comparison to placebo.
The objective of the current study is to explore the clinical benefits of using a combination of hydrocortisone, vitamin C, and thiamine (triple therapy) for the management of septic shock. To achieve this objective, we will compare two alternative treatment strategies, either triple therapy or usual care in patients with septic shock.
First aim: To assess the effectiveness of the triple therapy for septic shock Second aim: To assess the safety of triple therapy
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
- None
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
- •Age (above 18 years old)
- •Suspected or documented infection
- •Meeting the definition of septic shock (Sepsis 3 definitions); Patients with septic shock can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressor therapy to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L despite adequate volume resuscitation.
- •Receiving norepinephrine at a dose equal or more than 0.1 µg/kg/min for more than or equal 6 hours.
排除标准
- •Known pregnancy(1)
- •Primary diagnosis of acute cerebral vascular event
- •Acute coronary syndrome
- •Status asthmaticus
- •Major cardiac arrhythmia
- •Active gastrointestinal hemorrhage
- •Drug overdose
- •Burn or trauma
- •Requirement for immediate surgery(2)
- •Absolute neutrophil count <500 mm3
- •CD4 <50/mm³
- •Do-not-resuscitate status
- •Advanced directives restricting implementation of the protocol
- •Terminally ill patients in palliative care
- •Participation in another interventional study
- •Known allergy or contraindication to one or more of the trial medications (Vitamin C, Thiamine, or Hydrocortisone)
- •If the pregnancy status is unknown, the pregnancy test will not be done as part of the usual care, the patient is unconscious, and consent cannot be obtained for pregnancy test; we will not enroll the patient.
- •Patients with septic shock and requiring immediate surgery will be evaluated after surgery for inclusion.
研究组 & 干预措施
Triple therapy group
Experimental group will receive usual care according to Hamad Medical Corporation Adult Sepsis Care Pathway (CPW 10311, May 2017) PLUS triple therapy.
Triple therapy regimen:
Intravenous vitamin C (1.5 gm q 6 hourly for 4 days or until ICU discharge, whichever is earlier), hydrocortisone (50 mg q 6 hourly for 7 days or until ICU discharge, whichever is earlier, followed by a taper over 3 days) as well as intravenous thiamine (200 mg q 12 hourly for 4 days or until ICU discharge, whichever is earlier).
干预措施: Triple therapy group (Drug)
结局指标
主要结局
Hospital Mortality at 60 days
时间窗: 60 days after randomization
Patients died during hospital admission
次要结局
- Renal replacement therapy for acute kidney injury(60 days after randomization)
- Need for Extracorporeal membrane oxygenation (ECMO)(60 days after randomization)
- Time to death(60 days after randomization)
- Clinical evidence of organ dysfunction(72 hours after randomization)
- Length of ICU stay(60 days after randomization)
- Length of hospital stay(60 days after randomization)
- Duration of vasopressor therapy(60 days after randomization)
- Lactate clearance(72 hours)