Efficacy of Vitamin C on AKI Outcomes in Critically Ill Cirrhotics With Multidrug-resistant Bacterial Infections- A Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- AKI progression at day 5
研究概览
简要总结
In this prospective randomized controlled trial we aim to evaluate the impact of vitamin C on AKI outcomes in patients with cirrhosis and MDR infections. We also aim to evaluate the effects of iv vitamin c on systemic hemodynamics (cardiac output and systemic vascular resistive index, extravascular lung water and lung permeability index), endothelial function and coagulation, microcirculation (as assessed by lactate clearance and central venous oxygen saturation), mitochondrial function, 28-day mortality and vasopressor, ventilator and RRT free days in the ICU. The safety and side-effects of vitamin c would also be evaluated.
Patients with suspected (nosocomial acquisition) or proven MDR infections would be screened and randomized to two groups who meet the inclusion and exclusion criteria.
Group 1: Will receive iv vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as per institutional protocol Group 2: iv antibiotics alone
详细描述
Aim & Objectives Primary To evaluate the impact of vitamin C on AKI outcomes in patients with cirrhosis and MDR infections
Secondary Objectives To assess the effects on systemic hemodynamics (cardiac output and systemic vascular resistive index, extravascular lung water and lung permeability index) Impact of Vitamin C on endothelial function and coagulation Improvement in microcirculation as assessed by lactate clearance and central venous oxygen saturation To assess the effects on 28-day mortality. Improvement in SOFA scores in both groups Vasopressor, ventilator and RRT free days in the ICU Incidence of adverse effects in both groups Prevalence of vitamin C deficiency in cirrhotics with sepsis and impact of exogenous vitamin C in improving endogenous levels of ascorbate and norepinephrine levels Impact of vitamin C on oxidative stress by evaluation of mitochondrial bioenergetics
(B) Methodology Patients with suspected (nosocomial acquisition) or proven MDR infections would be screened and randomized to two groups as under Group 1: Will receive iv vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as per institutional protocol Group 2: iv antibiotics alone All patients with nosocomial bacterial infections or septic shock would be screened for randomization would be considered for enrolment in the trial. Nosocomial infection would be defined as infections developing after 48 hours of hospitalization. Following this, patients meeting the inclusion and exclusion criteria will be screened and randomized to the two treatment groups. Standard of care for management of antibiotics, fluids and vasopressors would be as per institutional guidelines. At baseline, blood and urine sample would be stored for all patients for performing mitochondrial bioenergetics, endotoxin, proinflammatory cytokines (IL-6, IL-IB, TNF-alpha, MCP-1, IL-1O) and urine biomarkers (urine NGAL and cystatin C) and markers of endothelial dysfunction(von willebrand factor and ADAMTS). Following randomization patients would be allocated to receive intravenous vitamin C (1.5 g every 6 h or 25 mg/kg for 5 days) along with intravenous antibiotics
Study Population:
Patients with cirrhosis with MDR infections (nosocomial acquisition) or culture-proven
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Critically ill cirrhotics with MDR infections
排除标准
- •Patients with age less than 18 years
- •Known severe cardiopulmonary disease (structural or valvular heart disease, coronary artery disease, COPD)
- •Patients in DIC with platelets < 20,000 and INR > 4 or active bleeding
- •Limitations of care (defined as refusal of cardiovascular and respiratory support modes) including "do not intubate" (DNI) status
- •Current hospitalization > 15 days for patients with nosocomial acquisition of MDR at time of randomization
- •Known allergy or contraindication to vitamin C (including previously or currently diagnosed primary hyperoxaluria and/or oxalate nephropathy, or known/suspected ethylene glycol ingestion,
- •Known glucose-6-phosphate dehydrogenase (G6PD) deficiency)
- •Use of vitamin C at a dose of > 1 gram daily within the 24 hours preceding first episode of qualifying organ dysfunction during a given ED or ICU admission
- •Patients with HCC (beyond Milan) or extrahepatic malignancies
- •Patients with HVOTO or EHPVO
- •Pregnancy or active breastfeeding
- •Current participation in another interventional research study
- •Active or history of kidney stone
- •History of chronic kidney disease or intrinsic kidney disease
- •Patients already on maintenance hemodialysis prior to presentation
- •Patients with refractory septic shock or hypoxemia (Pa02/Fio2 ratio <100)
- •Extremely moribund patients with an expected life expectancy of less than 24 hours
- •Failure to provide informed consent
- •Patients with retroviral infection
- •Patients with acute on chronic liver failure (APASL definition)
- •Patients with urinary tract infection
研究组 & 干预措施
Vitamin C + Standard Medical Treatment
vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as per institutional protocol along with iv antibiotics
干预措施: Vit C (Drug)
Vitamin C + Standard Medical Treatment
vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as per institutional protocol along with iv antibiotics
干预措施: Standard medical Treatment (Drug)
Standard Medical Treatment
iv antibiotics alone
干预措施: Standard medical Treatment (Drug)
结局指标
主要结局
AKI progression at day 5
时间窗: Day 5
次要结局
- Time to reversal of AKI in both groups(Day 14)
- Lactate clearance in both groups(24 hours)
- Vasopressor, ventilator and days free of dialysis during ICU stay(Day 28)
- Mortality in both groups(Day 28)