The Effects of Sildenafil for Liver Fibrosis in Adolescents and Adults After Fontan Operation: An Open-label, Randomized Controlled, Pilot Trial.
试验速览
- 阶段
- 4 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Liver MRI
研究概览
简要总结
Fontan operation is currently the most common procedure performed in patients with single-ventricle physiology. This surgery allows for passive caval blood flow to the pulmonary arteries in the absence of a subpulmonary pump and therefore separating the pulmonary circulation from systemic circulation. However, late hepatic complications such as liver fibrosis, cirrhosis, or even hepatocellular carcinoma are increasingly described in patients with Fontan circulation. The Fontan associated liver disease (FALD) is related to the decreased cardiac output and elevated central venous pressure after Fontan operation. Although the prevalence of FALD is higher than 90% in patients with Fontan circulation. There are no specific medications can reverse the liver fibrosis or prevent the progression of FALD at present. Sildenafil had been used in patients after Fontan operation not only to decrease their pulmonary vascular resistance and central venous pressure, increased systemic cardiac output. Comparing with other oral pulmonary vasodilators, sildenafil is with less possibility of liver toxicity. Therefore, we will conduct a prospective, open-labeled, randomized-controlled study in at least 90 Fontan patients with age > 12 years receiving follow -up at our institute. These patients will be in accordance with the ratio of 1: 1 distribution randomized into two groups, group 1 will receive sildenafil 20 mg three times daily for 3 years and the group will not receive any pulmonary vasodilator as a control. Patients in both group will receive the examinations of liver fibrosis markers, transient ultrasound elastography (FibroScan), diffusion-weighted magnetic resonance imaging (DW-MRI) and cardiopulmonary function test at baseline, 1 year, 2 years and 3 years after initiating treatment. Comparing the results of two groups, we may further clarify the treatment effect of sildenafil on FALD in patients after Fontan procedure.
详细描述
Research Design and Methods Patients and Methods
- Study cohort:
The adolescent and adult patients (age ≥ 12 years) with anatomic and/or functional univentricular heart receive Fontan procedure and are followed at our institute will be included in our study protocol. The expected sample size is 90 candidates, with the ratio of 1:1 distribution randomized into two groups. 2. Inclusion criteria:
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Patients age ≥ 12 years with anatomic and/or functional univentricular heart receive Fontan procedure followed at our institute (including the patients with heart failure or pregnancy).
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Patients without taking organic nitrates and not allergic to Sildenafil.
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Exclusion criteria:
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The patients cannot safely receive MRI examination, including patients with severe renal dysfunction, or after pacemaker or implantable cardioverter defibrillator implantation.
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Patients having known liver disease (such as viral hepatitis, alcoholic liver disease, etc.) other than FALD.
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Patients are under sildenafil or any pulmonary vasodilator therapy for lowering pulmonary resistance, or have been using any of these medications in recent 3 months.
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Methods:
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 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients age ≥ 12 years with anatomic and/or functional univentricular heart receive Fontan procedure followed at our institute (including the patients with heart failure or pregnancy).
- •Patients without taking organic nitrates and not allergic to Sildenafil.
排除标准
- •The patients cannot safely receive MRI examination, including patients with severe renal dysfunction, or after pacemaker or implantable cardioverter defibrillator implantation.
- •Patients having known liver disease (such as viral hepatitis, alcoholic liver disease, etc.) other than FALD.
- •Patients are under sildenafil or any pulmonary vasodilator therapy for lowering pulmonary resistance, or have been using any of these medications in recent 3 months.
研究组 & 干预措施
Treatment group
treatment group will administrate oral sildenafil 20 mg three times per day for 3 years
干预措施: Sildenafil 20 MG (Drug)
结局指标
主要结局
Liver MRI
时间窗: from baseline to 3 years
Intra-voxel incoherent motion (IVIM) imaging
次要结局
- Transient liver elastography(from baseline to 3 years)
- 6-minute walk test(from baseline to 3 years)
- cardiopulmonary function test(from baseline to 3 years)