The VitamIn C, HydrocorTisone and ThiAMINe in Patients With Septic Shock Trial (VITAMINS Trial) - A Prospective, Feasibility, Pilot, Multi-centre, Randomised, Open-label Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 216
- 试验地点
- 8
- 主要终点
- Time alive and free of vasopressors at day 7 (168 hours) after randomization.
研究概览
简要总结
Sepsis has been characterised as a dysregulated host response to infection. Adjunctive therapies targeting the inflammatory cascade are being increasingly explored, although to date, have failed to demonstrate consistent benefit, and sepsis continues to manifest poor outcomes. Hospital mortality in patients with septic shock remains as high as 22% in Australia and New Zealand. From a global perspective, 31 million sepsis and 19 million severe sepsis cases are expected to be treated in hospitals all over the world per year.
To date, experimental data have reported that both high dose intravenous vitamin C and corticosteroids attenuate the acceleration of the inflammatory cascade and possibly reduce the endothelial injury characteristic of sepsis, enhance the release of endogenous catecholamines and improve vasopressor responsiveness.
Therefore, the investigators plan to conduct a feasibility pilot prospective, multi-centre, randomised, open-label, trial in ICU patients with septic shock to test whether the intravenous administration of high dose Vitamin C (6g/d), Thiamine (400mg/d) and Hydrocortisone (200mg/d) leads to a more rapid resolution shock and vasopressor dependence.
详细描述
The investigators plan to conduct a feasibility pilot prospective, multi-centre, randomised, open-label, trial in ICU patients with septic shock to test whether the intravenous administration of high dose Vitamin C (6g/d), Thiamine (400mg/d) and Hydrocortisone (200mg/d) for a maximum of ten days leads to a more rapid resolution shock and vasopressor dependence.
Hypothesis:
Treatment with a combination of intravenous Vitamin C, Thiamine and Hydrocortisone reduces duration of vasopressor (measured by hours alive and vasopressor free) use censored at 7 days compared to standard care with Hydrocortisone alone.
This is a prospective, feasibility, pilot, multi-centre, randomised, open-label controlled trial. This study will be performed in seven Victorian ICUs in Australia. Patients admitted to an ICU of the participating hospitals with the primary diagnosis of septic shock will be screened for inclusion into this study.
Rationale:
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
- •Patient in the intensive care unit (ICU) with septic shock:
- •Blood lactate >2 mmol/L, despite adequate fluid resuscitation AND
- •need for continuous vasopressor therapy to keep mean arterial pressure (MAP) >65 mmHg for >2 hours
排除标准
- •Age < 18 years
- •DNR (do not resuscitate)/DNI (do not intubate) orders
- •Death is deemed to be imminent or inevitable during this admission, and either the attending physician, patient or substitute decision-maker is not committed to active treatment
- •Patients with known HIV infection
- •Patients with known glucose-6 phosphate dehydrogenase (G-6PD) deficiency
- •Patients transferred from another ICU or hospital with a diagnosis of a septic shock for > 24 hours
- •Patients with a diagnosis of a septic shock for > 24 hours
- •Patients with known or suspected
- •a. history of oxalate nephropathy or hyperoxaluria
- •b. short bowel syndrome or severe fat-malabsorption
- •c. acute beri-beri disease
- •d. acute Wernicke's encephalopathy
- •e. malaria
- •f. scurvy
- •g. Addison's disease
- •h. Cushing's disease
- •Clinician expects to prescribe systemic glucocorticoids for an indication other than septic shock (not including nebulised or inhaled corticosteroid)
- •Patient is receiving treatment for systemic fungal infection or has documented Strongyloides infection at the time of randomisation
- •Patient with known chronic iron overload due to iron storage and other diseases
- •Patient previously enrolled in this study
- •Clinician expects to prescribe high dose vitamin C for another indication
研究组 & 干预措施
Vitamins
intravenous: Ascorbic acid (Vitamin C: 1.5g every 6 hours) Thiamine (Vitamin B1: 200mg every 12 hours) Hydrocortisone (50mg every 6 hours)
干预措施: Vitamin C (Drug)
Vitamins
intravenous: Ascorbic acid (Vitamin C: 1.5g every 6 hours) Thiamine (Vitamin B1: 200mg every 12 hours) Hydrocortisone (50mg every 6 hours)
干预措施: Thiamine (Drug)
Vitamins
intravenous: Ascorbic acid (Vitamin C: 1.5g every 6 hours) Thiamine (Vitamin B1: 200mg every 12 hours) Hydrocortisone (50mg every 6 hours)
干预措施: Hydrocortisone, (Drug)
Control
Hydrocortisone (50mg every 6 hours)
干预措施: Hydrocortisone, (Drug)
结局指标
主要结局
Time alive and free of vasopressors at day 7 (168 hours) after randomization.
时间窗: 7 days (168 hours)
This is defined by the patient being alive at discontinuation of all vasopressors for at least 4 hours in the presence of a MAP\>65 mmHg for the same 4 hour period as recorded in the ICU charts and censored at 7 days. If a patient dies while on vasopressor therapy, in such a patient, the time alive and vasopressor free time will be 0 - This approach will correct for the competing effect of mortality on duration of vasopressor therapy.
次要结局
- Hospital mortality(90 days after randomization)
- Alive and ICU-free days at day 28 calculated as the number of days alive and out of the ICU to day 28(28 days after randomization)
- 28-day mortality(28 days after randomization)
- ICU mortality(90 days after randomization)
- 90-day mortality(90 days after randomization)
- 28 day cumulative invasive mechanical ventilation free hours(28 days after randomization)
- Delta of Sequential Organ Failure Assessment (SOFA) score at 72 hours(72 hours after randomization)
- Hospital length of stay(90 days after randomization)
- 28 day cumulative vasopressor free hours(28 days after randomization)
- RRT duration(28 days after randomization)
研究者
anzicrc
Professor Rinaldo Bellomo
Australian and New Zealand Intensive Care Research Centre