Midodrine and Albumin in Patients With Refractory Ascites. A Randomised Controlled Trial.
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 114
- 主要终点
- Number of patients with control of ascites at 1 year
研究概览
简要总结
Refractory ascites is seen in 5-10% of patients with cirrhosis.Decompensated cirrhosis with refractory ascites has a mortality rate of around 40% in a year and a median survival of 6 months.Portal hypertension and splanchnic vasodilation are major factors in the development of ascites.The treatment of refractory ascites involves salt restriction, diuretics, large volume paracentesis (LVP), transjugular Intrahepatic Portosystemic shunt (TIPS) and Liver Transplantation (LT). Currently the only curative treatment is LT. However, LT is limited due to organ shortage and high cost.
Long-term human albumin (HA) administration in patients with uncomplicated and refractory ascites, has shown to improve survival or delay the complications of cirrhosis. Midodrine, an oral α1- adrenergic agonist has been used in refractory ascites with variable results. However, there is no study on the use of long term Midodrine and HA in patients with refractory ascites. Therefore, we plan to study the effect of long term midodrine and HA in patients with refractory ascites.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 80 years
- •Refractory ascites in cirrhosis of any etiology
排除标准
- •Mixed ascites: cirrhosis plus another cause of ascites
- •Gastrointestinal bleed within 7 days of enrolment.
- •Presence of hepatorenal syndrome
- •Hepatic encephalopathy grade 2 or higher
- •Infection within 1 month preceding the study
- •Cardiovascular disease (ejection fraction < 35% or abnormal ECG) or arterial hypertension (BP > 140/90 mm of Hg)
- •Abnormal urine analysis with proteinuria > 500 mg/24 hour or 50 red blood cells/high power field, or granular casts or ultrasonographic evidence of intrinsic renal disease
- •Presence of hepatocellular carcinoma or portal vein thrombosis
- •Treatment with drug with known effects on systemic and renal hemodynamics within 7 days of inclusion excepting beta-blockers
- •Patient not willing for study.
- •Patient opting for liver transplantation/ transjugular intrahepatic portosystemic shunt
研究组 & 干预措施
Albumin + Midodrine + SMT
Human albumin plus oral midodrine
干预措施: Albumin (Drug)
Albumin + Midodrine + SMT
Human albumin plus oral midodrine
干预措施: Midodrine (Drug)
Albumin + Midodrine + SMT
Human albumin plus oral midodrine
干预措施: Standard medical therapy (SMT) (Drug)
Albumin + SMT
Human albumin plus placebo of midodrine
干预措施: Albumin (Drug)
Albumin + SMT
Human albumin plus placebo of midodrine
干预措施: Standard medical therapy (SMT) (Drug)
SMT
standard medical therapy plus placebo of midodrine
干预措施: Standard medical therapy (SMT) (Drug)
结局指标
主要结局
Number of patients with control of ascites at 1 year
时间窗: 1 year
Control of ascites will be defined as- * Complete response will be total absence of ascites. * Partial response as presence of ascites not requiring paracentesis * Non response will be defined as persistence of severe ascites requiring paracentesis.
次要结局
- Changes in concentration of albumin at 3 months intervals(1 year)
- Change in Child-Turcotte-Pugh (CTP) score(1 year)
- Change in estimated glomerular filtration rate (eGFR) measured by modified diet in renal disease 6 (MDRD6) formula at 3 months intervals(1 year)
- Changes in serum and 24- hour urine sodium(1 year)
- Incidence of spontaneous bacterial peritonitis (SBP) and other infections(1 year)
- Number of patients who develop hypokalemia(1 year)
- Number of patients who develop hyperkalemia(1 year)
- Change in model for end stage liver disease (MELD) score(1 year)
- Change in mean arterial pressure at 3 months interval(1 year)
- Number of patients who develop paracentesis induced circulatory dysfunction (PICD)(1 year)
- Number of patients who develop hyponatremia(1 year)
研究者
Dr.Virendra Singh
Professor and Head, Department of Hepatology
Post Graduate Institute of Medical Education and Research, Chandigarh