Midodrine Plus Albumin Versus Midodrine Alone to Prevent Cirrhosis Related Complications in Children With Cirrhosis and Ascites - An Open Label Randomized Controlled Trial.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 2
- 主要终点
- To compare difference in composite incidence of complications of cirrhosis (Acute kidney injury, ascites, hyponatremia, hepatic encephalopathy) in patients receiving midodrine and albumin versus those receiving midodrine alone.
研究概览
简要总结
Children with decompensated cirrhosis are more prone to develop various complications. The pathogenesis of cirrhotic complications (ascites, hyponatremia, acute kidney injury) includes release of vasodilatory molecules like nitric oxide, damage associated molecular pathogens (DAMPs) and pattern associated molecular pathogens (PAMPs) secondary to bacterial translocation, which causes splanchnic bed vasodilation resulting in activation of renin-angiotensin and aldosterone axis (RAAS) causing sodium and water retention and renal vasoconstriction.
The development of complications in these children may result in death or may preclude them from reaching upto liver transplantation.
Midodrine is an α1 adrenergic receptor agonist, which increases vascular tone causing rise in the blood pressure, thereby improving renal perfusion and causes RAAS deactivation. The effects of midodrine is documented in reduction of refractory ascites, hepatorenal syndrome and hyponatremia.
Albumin is a protien that works by both increasing the colloidal oncotic pressure and improving systemic circulation as well as by effecting the body with anti-inflammatory and antioxidant properties.
We have already demonstrated the safety and efficacy of midodrine as well as albumin in cirrhotic children. However, none of these drugs alone provided survival benefit to the patients. Hence, we have planned this study with the ojective to evaluate if combining these 2 drugs (midodrine and albumin) would further reduce the complications and improve the survival in decompensated cirrhotic children.
详细描述
Aim: To evaluate whether a combination of midodrine and intravenous albumin reduces complications of cirrhosis in decompensated (ascites) cirrhotic children as compared to midodrine alone.
Primary objective: To compare difference in composite incidence of complications of cirrhosis (Acute kidney injury, ascites, hyponatremia, hepatic encephalopathy) in patients receiving midodrine and albumin versus those receiving midodrine alone.
Secondary objectives:
- To compare the rate of control of ascites by 6 months in the 2 groups
- To compare the change in Mean arterial pressure (MAP) at 1 week, 2 weeks, 4 weeks, 3 months, and 6 months in the 2 groups
- To compare the Plasma renin activity at baseline, 4 weeks, 3mo, 6mo in the 2 groups
- Evaluate the change in serum sodium from baseline to 6 months in the 2 groups
- To compare the Creatinine from baseline to 6 months in the 2 groups
- To compare the Frequency of development of drug related adverse effects by 6 months
- To compare the Transplant free survival in the 2 groups
- To compare the Cytokines levels at baseline and 6 months in the 2 groups
- To compare the presence of Minimal Hepatic encephalopathy in the 2 groups Study population :Children and Adolescents of age group upto 18 years with decompensated cirrhosis with clinical ascites, following up in the Pediatric Hepatology Department, ILBS will be prospectively included in this study after informed consent
- Study design: Open-label Randomized Controlled Trial
- Study period: 6 months weeks for each patient; The study will be conducted from the time of ethical approval to June 2025.
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
- 12 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children (≤ 18 years)
- •Cirrhosis based on histological/ radiological + endoscopic evidence
- •Clinical ascites (≥ grade 2 ascites)
- •Informed consent from parents (Assent > 12 years)
排除标准
- •Arterial hypertension (Mean Arterial Pressure ≥ 95th centile for age)
- •Presence of Portal vein thrombosis
- •Hepatorenal Syndrome
- •Congestive Heart failure
- •Respiratory failure(PF ratio <200)
- •Septic shock
- •Presence of Hepatocellular Carcinoma
- •Transjugular intrahepatic Porto Systemic Shunt
研究组 & 干预措施
Midodrine+Albumin+SMT
- Albumin infusion 1g/kg/day (max 20g) every two weeks (if pre-infusion serum albumin is < 3.5 gm/dl Plus
- Midodrine starting at 0.25mg/kg/day in divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% .
In addition, standard medical therapy will be administered to patients in both the arms.
干预措施: Midodrine (Drug)
Midodrine+Albumin+SMT
- Albumin infusion 1g/kg/day (max 20g) every two weeks (if pre-infusion serum albumin is < 3.5 gm/dl Plus
- Midodrine starting at 0.25mg/kg/day in divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% .
In addition, standard medical therapy will be administered to patients in both the arms.
干预措施: albumin (Biological)
Midodrine+Albumin+SMT
- Albumin infusion 1g/kg/day (max 20g) every two weeks (if pre-infusion serum albumin is < 3.5 gm/dl Plus
- Midodrine starting at 0.25mg/kg/day in divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% .
In addition, standard medical therapy will be administered to patients in both the arms.
干预措施: Standard Medical Treatment (Other)
Midodrine+SMT
• Midodrine starting at 0.25mg/kg/day in divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% In addition, standard medical therapy will be administered to patients in both the arms.
干预措施: Midodrine (Drug)
Midodrine+SMT
• Midodrine starting at 0.25mg/kg/day in divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% In addition, standard medical therapy will be administered to patients in both the arms.
干预措施: Standard Medical Treatment (Other)
结局指标
主要结局
To compare difference in composite incidence of complications of cirrhosis (Acute kidney injury, ascites, hyponatremia, hepatic encephalopathy) in patients receiving midodrine and albumin versus those receiving midodrine alone.
时间窗: 6 months
次要结局
- To compare the Frequency of development of drug related adverse effects by 6 months(6 months)
- To compare the Transplant free survival in the 2 groups(6 months)
- To compare the change in Mean arterial pressure (MAP) at 1 week, 2 weeks, 4 weeks, 3 months, and 6 months in the 2 groups(1 week, 2 weeks, 4 weeks, 3 months, and 6 months)
- Evaluate the change in serum sodium from baseline to 6 months in the 2 groups(6 months)
- To compare the Cytokines levels at baseline and 6 months in the 2 groups(6 months)
- To compare the presence of Minimal Hepatic encephalopathy in the 2 groups(6 months)
- To compare the Creatinine from baseline to 6 months in the 2 groups(6 months)
- To compare the rate of control of ascites by 6 months in the 2 groups(6 months)
- To compare the Plasma renin activity at baseline, 4 weeks, 3mo, 6mo in the 2 groups(baseline, 4 weeks, 3months, 6months)