Acute Hemodynamic Response to Carvedilol in Children With Clinically Significant Portal Hypertension.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Proportion of children with acute hemodynamic response 90 mins after carvedilol given through nasogastric route) in those with clinically significant portal hypertension.
研究概览
简要总结
Clinically significant portal hypertension (CSPH) is defined as Hepatic Venous Pressure gradient (HVPG) >10 mmHg. Patients with CSPH are at risk of developing esophageal varices and clinical decompensation (variceal bleeding, ascites, jaundice, encephalopathy), which mark the transition from compensated stage to a stage of the disease (decompensated) associated with higher mortality. HVPG is calculated by subtracting the free hepatic venous pressure (FHVP), a measure of systemic pressure, from the wedged hepatic venous pressure (WHVP), a measure of hepatic sinusoidal pressure. HVPG is surrogate marker in many clinical applications such as gold standard test to evaluate presence and severity of portal hypertension (PHT) diagnosis, risk stratification, monitoring of the patients on beta blockers. Non-selective beta-blockers like propranolol and carvedilol are indicated in adults for primary and secondary prophylaxis of variceal hemorrhage. Acute hemodynamic response to intravenous propranolol with HVPG values coming down to < 12 mm Hg or reduction to >20% from baseline have been shown to be associated with reduced long-term risk of variceal bleed. Portal Hypertension in biliary atresia (BA) occurs early and is due to recurrent cholangitis and portal sclerosis. HVPG in children is feasible and safe in children according to previous studies, however, there are no recommendations to suggest beta-blockers based on HVPG reduction in children. Hence, we are planning the current work to study the acute hemodynamic response to carvedilol in children with CSPH, and to compare the HVPG values in children with chronic liver disease.
详细描述
Aim: To study acute hemodynamic response Hepatic Venous Pressure Gradient (HVPG) reduction to <12 mm Hg or by ≥ 20% from initial value) to carvedilol in from 2 to 18 year of age children with Chronic liver disease.
Methodology Study population: All children (2-18) years of age with CLD as per inclusion and exclusion criteria
Study design: Prospective cohort
Baseline parameters that will be recorded:
- Baseline characteristics:
- History and etiology of liver disease
- Symptomatology, Evidence of decompensation (jaundice,organomegaly, encephalopathy, ascites, infections, variceal bleed etc)
- Clinical and demographic profile
- Variceal bleed, ascites, infections, hepatic encephalopathy, AKI
- Endoscopic findings:
- Esophageal varices
- Red colour signs
- Gastric varices
- Clinically significant varices
- Portal hypertensive gastropathy
- Liver and splenic stiffness
- Splenic Z-score - based on ultrasound measure of spleen (in cm) and calculation of Z-scores based on centiles from Indian children
- Anthropometric parameters:
- Weight for age
- Height for age
- Weight for length
- BMI
- Triceps skin fold thickness
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All children 2-18 years of age with CLD defined as presence of either of the following histological evidence of advanced fibrosis more than F2 on METAVIR staging or radiological imaging suggestive (heterogeneous hepatic echotexture, irregular nodular liver and/or caudate hypertrophy). .
- •Splenomegaly and/or platelets </= 100 (X10^3/mm3)
- •Coming for upper gastrointestinal endoscopy for variceal screening
- •Informed consent for HVPG and UGIE
排除标准
- •Uncorrected heart defects (except small ASD)
- •Cardiac conduction defects - arrythmias or heart block
- •Interrupted inferior vena cava
- •Situs inversus
- •Patients who received beta-blockers in last 7 days
- •Patients who received Octreotide infusion or bolus in last 7 days
- •Variceal bleed in last 48 hours
- •Shock or active sepsis
- •Grade 2 /grade 3 ascites
- •Severe hepatic impairment with MELD or PELD score >14
- •Acute kidney injury (any grade)
- •Hepatic encephalopathy (any grade)
- •Known contraindications to propranolol in children:
- •Hyper-reactive airway disease
- •Hypertrophic cardiomyopathy
- •Acute congestive heart failure
研究组 & 干预措施
Carvedilol for 1.5 hrs
Carvedilol 0.2 mg/kg for 1.52 hrs
干预措施: Carvedilol (Drug)
结局指标
主要结局
Proportion of children with acute hemodynamic response 90 mins after carvedilol given through nasogastric route) in those with clinically significant portal hypertension.
时间窗: 90 minutes
Acute hemodynamic response (HVPG reduction to less than 12 mm Hg or by more than equals to 20% from initial value
次要结局
- Splenic Z-scores, Liver and splenic stiffness in children with HVPG more than equal to 10 or less than 10 mm Hg in different etiologies of liver disease.(Day 0)
- HVPG values in children (2-18 years age) with different etiologies of chronic liver disease.(Day 0)
- Risk factors of acute hemodynamic response on univariate and multivariate binary logistic regression analysis.(Day 0)
- Proportion of children with presence of varices and clinically significant varices in children with HVPG less than 10 mm Hg in different etiologies of liver disease.(Day 0)
- Bile acid levels in children with HVPG more than equal to 10 or less than 10 mm Hg in different etiologies of liver disease.(Day 0)
- Change in the grading (low or high risk) of esophageal varices at 6 months after starting oral carvedilol in children with or without acute hemodynamic response.(6 months)
- Proportion of children with presence of varices and clinically significant varices in children with HVPG more than equal to 10 in different etiologies of liver disease..(Day 0)