Safety and Efficacy of Continuous Infusion of Terlipressin With Norepinephrine Versus Norepinephrine Alone in Improving Outcomes of Acute Kidney Injury in Acute on Chronic Liver Failure With Septic Shock - A Randomised Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 126
- 试验地点
- 1
- 主要终点
- Proportion of patients developing 1 stage improvement in Acute kidney injury stage with resolution of shock at day 4 in both groups
研究概览
简要总结
ACLF is defined differently in APASL,EASL and AASLD.APASL talks of reversibility in ACLF as per its definition and constitution of Homogenous population with ACLF.The definition of ACLF as per APASL is an acute hepatic insult manifesting as jaundice (serum bilirubin ≥ 5 mg/dL (85 micromol/L) and coagulopathy (INR ≥ 1.5 or prothrombin activity < 40%) complicated within 4 weeks by clinical ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease/cirrhosis, and is associated with a high 28-day mortality.
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.
Currently, Norepinephrine is recommended as the first vasopressor to be started in general in septic shock population.(3) Catecholamines are the clinically used vasopressor agents of choice for supporting arterial blood pressure and ensuring adequate organ perfusion.
Development of adrenergic hyposensitivity with loss of catecholamine presser effects is seen in advanced stages of Vasodilatory Shock. Progressively increasing catecholamine therapy frequently enters into a vicious cycle of major adverse side effects resulting in continuous clinical deterioration necessitating further catecholamine excess.
详细描述
• Aim: To study the safety and efficacy of low-dose continuous infusion of terlipressin with norepinephrine compared to norepinephrine alone in improving outcomes of Acute kidney injury occurring in the context of septic shock in patients with Acute on chronic liver failure.
Study population:
- septic shock with AKI in patients of ACLF
Study design: Prospective open labelled randomised controlled study. The study will be conducted in Department of Hepatology ILBS- intensive care unit.
At admission:
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age>18 years and <60 yrs
- •ACLF as per APASL
- •AKI according to KDIGO Criteria
- •septic shock requiring norepinephrine (<0.05mcg/kg/min).
排除标准
- •Septic shock requiring 2 vasopressors (Norephinephrine reuirement > 0.05mcg/kg/min)
- •Symptomatic cardiopulmonary disease
- •Chronic kidney disease
- •Peripheral vascular disease
- •Hepatocellular carcinoma outside Milan criteria
- •Prior use of terlipressin in last 48 hours
- •Patients with hypovolemic or hemorrhagic shock
- •Patients already meeting criteria for dialysis or with history of dialysis in last 7 days
- •Intrinsic kidney disease, Acute tubular necrosis with urinary output < 400 ml /day or obstructive uropathy
- •History of immunosuppressive drugs
- •Human immunodeficiency virus 1 and 2
- •Portal vein thrombus
研究组 & 干预措施
Continuous terlipressin infusion + Norepinephrine
- Patients in this group will receive continuous terlipressin infusion (1 mg/24 hr on day 1, increasing to 1 mg in 24 hours if target MAP not achieved ,reaching maximum terlipressin dose of 4 mg/24 hr on day 4).If target MAP not achieved by terlipressin dose ,increase noradrenaline dose keeping terlipressin maximum 1 mg ,2 mg ,3mg ,4mg at Day 1,2,3,4 respectively.
- Norepinephrine will be initiated @0.05mcg/kg/min and titrated upto 0.5 mcg/kg/min to maintain a MAP > 65 to 75 mm Hg.
- IV albumin as per volume status to maintain target MAP .
- If the target MAP is not achieved, a third vasopressor along with hydrocortisone, Adrenaline and then phenylephrine.
干预措施: Terlipressin (Drug)
Continuous terlipressin infusion + Norepinephrine
- Patients in this group will receive continuous terlipressin infusion (1 mg/24 hr on day 1, increasing to 1 mg in 24 hours if target MAP not achieved ,reaching maximum terlipressin dose of 4 mg/24 hr on day 4).If target MAP not achieved by terlipressin dose ,increase noradrenaline dose keeping terlipressin maximum 1 mg ,2 mg ,3mg ,4mg at Day 1,2,3,4 respectively.
- Norepinephrine will be initiated @0.05mcg/kg/min and titrated upto 0.5 mcg/kg/min to maintain a MAP > 65 to 75 mm Hg.
- IV albumin as per volume status to maintain target MAP .
- If the target MAP is not achieved, a third vasopressor along with hydrocortisone, Adrenaline and then phenylephrine.
干预措施: Norephrine (Drug)
Norepinephrine
- Patients in this group will receive norepinephrine only, with a dose range of 0.05 mcg/kg/min to 0.5 mcg/kg/min to maintain a MAP > 65 to 75 mm Hg.
- IV albumin as per volume status to maintain target MAP .
- If the target MAP is not achieved, vasopressin along with hydrocortisone, followed by adrenaline and phenylephrine, may be added as a fourth vasopressor.
干预措施: Norephrine (Drug)
结局指标
主要结局
Proportion of patients developing 1 stage improvement in Acute kidney injury stage with resolution of shock at day 4 in both groups
时间窗: Day 4
次要结局
- Duration of ICU and hospital stay(1 year)
- Incidence of adverse events in both groups(1 year)
- Outcome of acute kidney injury at day 4,7(Day 4 and 7)
- Mortality(Day 7 and 28)
- Need of renal replacement therapy at day 7(Day 7)