To Assess the Efficacy of Midodrine in Prevention of Cirrhosis Related Complications in Children Awaiting Liver Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Complications between the two groups
研究概览
简要总结
Children with cirrhosis awaiting transplantation are more proned 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 [1].
The development of complications in these children may result in death or may preclude them from reaching upto liver transplantation [2].
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[2-4].
One group will receive only standard medical therapy and other group will receive midodrine and standard medical therapy for 6 months. Mean arterial pressure will be monitored at every OPD visit. At the end of 12 weeks, and 24 weeks, plasma renin activity, incidence of complications related to cirrhosis like new onset ascites, increase in grade of ascites, hyponatremia, acute kidney injury and spontaneous bacterial peritonitis will be assessed. Also the transplant free survival and need for albumin transfusion will be compared between the two groups.
In case of liver transplantation or death before 6 months, midodrine will be stopped
详细描述
Aim: To determine the efficacy of midodrine in preventing development of complications in children with cirrhosis awaiting liver transplantation
Primary Objective:
- To compare incidence of complications (Acute kidney injury, New onset ascites or increase in grade of ascites, Spontaneous bacterial peritonitis, Hyponatremia, Hepatic encephalopathy) of cirrhosis in patients receiving midodrine (at a dose of 0.25 - 0.5mg/kg/day) and standard medical therapy versus standard medical therapy alone for 6 months
Secondary Objectives:
- Frequency of development of new onset ascites or increase in grade of ascites by 6 months
- Change in serum sodium from baseline to 6 months
- Change in Mean arterial pressure (MAP) at 1 week and then 2 weekly till the end of the study
- Plasma renin activity at baseline, at 12 weeks and 24 weeks
- Frequency of development of SBP over 6 months
- Change in eGFR from baseline to 6 months
- Frequency of developing AKI by 6 months
- Frequency of development of Hepatic encephalopathy by 6 months
- Proportion of patients developing hypertension at 6 months
- Frequency of development of drug related adverse effects by 6 months
- Requirement of albumin infusion in 2 groups
- Transplant free survival
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
- 10 Days 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children and Adolescents of age group upto 18 years with cirrhosis and PELD/ MELDNa score more than 14, on waitlist for liver transplantation following up in the Pediatric Hepatology Department, ILBS will be prospectively included in this study after informed consent
排除标准
- •Presence of Portal vein thrombosis Renal or cardiovascular disease or arterial hypertension Presence of HCC
研究组 & 干预措施
Midodrine
Midodrine starting at 0.25mg/kg/day in 2-3 divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% ; Midodrine dosage will be decreased by 25% in case of arterial hypertension (>95th centile BP for the age). Also Standard medical therapy as per departmental protocol will be continued
干预措施: Midodrine Oral Tablet (Drug)
Midodrine
Midodrine starting at 0.25mg/kg/day in 2-3 divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by >10% ; Midodrine dosage will be decreased by 25% in case of arterial hypertension (>95th centile BP for the age). Also Standard medical therapy as per departmental protocol will be continued
干预措施: Standard Medical Treatment (Other)
Standard medical therapy
Standard medical therapy as per departmental protocol
干预措施: Standard Medical Treatment (Other)
结局指标
主要结局
Complications between the two groups
时间窗: 6 months
• To compare incidence of complications (Acute kidney injury, New onset ascites or increase in grade of ascites, Spontaneous bacterial peritonitis, Hyponatremia, Hepatic encephalopathy) of cirrhosis in patients receiving midodrine (at a dose of 0.25 - 0.5mg/kg/day) and standard medical therapy versus standard medical therapy alone for 6 months
次要结局
- • Frequency of development of new onset ascites or increase in grade of ascites by 6 months(6 months)
- Plasma renin activity at baseline, at 12 weeks and 24 weeks(6 months)
- Frequency of developing AKI by 6 months(6 months)
- Proportion of patients developing hypertension at 6 months(6 months)
- Change in Mean arterial pressure (MAP) at 1 week and then 2 weekly till the end of the study(6 months)
- Frequency of development of drug related adverse effects by 6 months(6 months)
- Requirement of albumin infusion in 2 groups(6 months)
- Frequency of development of Hepatic encephalopathy by 6 months(6 months)
- Transplant free survival(6 months)
- Frequency of development of SBP over 6 months(6 months)
- Change in serum sodium from baseline to 6 months(6 months)
- Change in eGFR from baseline to 6 months(6 months)