Efficacy and Safety of Vasopressin Versus Terlipressin as a Second Vasopressor in Critically Ill Cirrhotics With Septic Shock- the VITEL-C Trial.
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Improvement in systemic hemodynamics at 6 hours after randomization
研究概览
简要总结
Sepsis is a life-threatening organ dysfunction caused by dysregulated host response. A Subset of sepsis is septic shock which has almost 4-6 times the mortality when compared to sepsis. Septic shock has underlying cellular and metabolic abnormalities in addition to circulatory dysfunction. The circulatory dysfunction in sepsis is in the form of severe vasodilatation with high cardiac index. Cirrhosis is a state of hyperdynamic circulation. The mortality of septic shock in these group of patients is still higher.
At the onset of septic shock there is initially an increased secretion of Arginine vasopressin. However, this initial rise is short lasting, and the vasopressin levels come back to normal or low serum levels with continued hypotension. However, even normal levels are too low for the degree of hypotension in septic shock. This causes a relative deficiency of vasopressin in septic shock. The exact time when this fall happens is not known and it is likely to be variable. Vasopressin was therefore tried as an agent in septic shock. Terlipressin is a synthetic analogue of vasopressin. It has a greater selectivity for the V1 receptor. Terlipressin is also shown to be effective in septic shock in cirrhotics3. Other vasoactive agents are not preferred in cirrhotics - dopamine due to high risk of arrhythmias and dobutamine as baseline cardiac output of cirrhotics is high which further increases in sepsis and dobutamine would further add to it. However, it may be given in myocardial dysfunction. Noradrenaline is recommended as the first vasopressor to be started in general in septic shock population. No study has compared the effectiveness of vasopressin and Terlipressin when added to noradrenaline in patients with cirrhosis. Acute kidney injury is a very common complication of septic shock in cirrhotics.
详细描述
Hypothesis: We hypothesise that vasopressin would be non-inferior to terlipressin as a second vasopressor in critically ill cirrhotics with septic shock and would have lesser adverse effects when compared to terlipressin.
Aim: To compare the efficacy of adding continuous infusion of terlipressin versus vasopressin to noradrenaline in causing improvement in systemic hemodynamics and microcirculation.
Methodology:
Study population:
- Critically ill cirrhotic - Defined as a cirrhotic patient who presents with at least one organ failure, defined by SOFA score WITH
- septic shock - Defined as a patient in septic shock after initial fluid resuscitation and antibiotic administration, requiring a noradrenaline of at least 2.6mcg/min to maintain a MAP more than 65mmHg.
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
- •Age 18-70yrs
- •An informed consent from the patient or relative
排除标准
- •Age <18 years and > 70 years
- •Severe sepsis requiring higher dose of noradrenaline (>1mcg/Kg/min)
- •Myocardial dysfunction, Coronary artery disease, Arrhythmias
- •Peripheral Vascular disease
- •Gut Paralysis
- •Acute on chronic liver failure (ACLF)
- •Hepato-cellular carcinoma (HCC), intrahepatic or extrahepatic malignancy
- •Complete portal vein thrombosis
- •Hepatic vein outflow tract obstruction (HVOTO)
- •Patients with Pa02/FiO2 ratio <150
- •Severe coagulopathy - platelets <20,000 and INR > 4
- •Active Bleed or DIC
- •Patients already on terlipressin or vasopressin in the last 48 hours
- •Extremely moribund patients with an expected life expectancy of less than 24 hours
- •Failure to give informed consent from family members.
- •Patient enrolled in other clinical trial
研究组 & 干预措施
Terlipressin
Terlipressin 1mg/24 hours
干预措施: Terlipressin (Drug)
Vasopressin
Vasopressin 0.03 U/hour
干预措施: vasopressin (Drug)
结局指标
主要结局
Improvement in systemic hemodynamics at 6 hours after randomization
时间窗: 6 hours after randomization
Improvement in systemic hemodynamics defined as discontinuation of noradrenaline infusion OR reversal of shock
次要结局
- Improvement in SVR by 10% or above 500 at 12 hours(12 hours)
- Improvement in SVR by 10% or above 500 at 48 hours(48 hours)
- KDIGO criteria - increase in urine output in 6 hours(6 hour)
- KDIGO criteria - increase in urine output in 48 hours.(48 hour)
- Improvement in microcirculation as measured by improvement in lactate(48 hours)
- Improvement in microcirculation as measured by improvement in capillary refill time at 6 hours(6 hours)
- Reduction in dose of noradrenaline at the end of 6 hours(6 hours)
- KDIGO criteria - increase in urine output in 12 hours.(12 hour)
- Amount of noradrenaline requirements between in each arm at the end of 6 hours(6 hours)
- Incidence of adverse effects till 48 hours after randomization including incidence of rebound hypertension(48 hours)
- Decrease in Cardiac output by 10% or less than 6L after 6 hours of randomization(6 hour of randomization)
- Need of Renal Replacement Therapy(Day 28)
- Improvement in microcirculation as measured by improvement in capillary refill time at 48 hours.(48 hours)
- Improvement in renal resistive index at 48 hours(48 hours)
- Days of Intensive Care Unit stay.(Day 28)
- Endothelial function will be measured in a subset of patients(48 hours)
- Days of mechanical ventilation(Day 28)
- Improvement in Systemic Vascular Resistance (SVR) by 10% or above 500 at 6 hours(6 hours)
- KDIGO criteria - increase in urine output in 24 hours(24 hour)
- Improvement in serum creatinine in 48 hours (Improvement in KDIGO stage at 48 hours)(48 hour)
- Coagulation function will measure in a subset of patients(48 hours)
- improvement in serum creatinine in 24 (Improvement in KDIGO stage at 24)(24 hour)
- Improvement in microcirculation as measured by improvement in capillary refill time at 24 hours.(24 hours)
- Improvement in microcirculation as measured by Near IR spectroscopy ina subset of patients whenever feasible(48 hours)
- Improvement in renal resistive index at 24 hours(24 hours)
- Mortality at day 28(Day 28)