Efficacy of Targeted And Response-Guided Albumin Therapy Versus Standard Medical Treatment In Outcomes Of Recurrent Ascites In Patients With Decompensated Cirrhosis- A Randomized Controlled Trial".
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Mortality in both groups
研究概览
简要总结
The current prospective randomized controlled trial would aim to study the efficacy of targeted albumin therapy versus standard medical treatment in reduction in 6-month mortality in recurrent ascites in patients with decompensated cirrhosis. Additionally, we aim to evaluate the efficacy of albumin in decreasing the incidence of complications: paracentesis induced circulatory dysfunction (PICD), AKI, hyponatremia, bacterial infections, hepatic encephalopathy and variceal bleed, impact on systemic hemodynamics and portal pressures, renal reserve as assessed by biomarkers and on immunomodulation. In this open labeled randomized study, consecutive cirrhotic patients, fulfilling the inclusion criteria and exclusion criteria will be enrolled in the study.
The patients will be randomized to 2 groups by the clinical trial coordinator (CTC). The CTC will be blind to the patient and treatment received, and the allocation concealment by the sequentially numbered opaque sealed envelopes (SNOSE) technique would be done. Patients would be assessed every 2 weeks for first 8 weeks with serum albumin levels, ascites grade and use of diuretics and then every 3 months. The treatment would receive targeted albumin therapy as detailed in methods while patients in the other group would receive standard medical treatment. The primary outcome of the study would be evaluation of 6-month mortality while secondary outcome measures would be the incidence of liver-related complications at 3, 6 and 12 months, survival free of liver transplant and TIPS in both groups at 6 months and 1 year, improvement in quality of Life as assessed by short form survey-36 version (SF-36) at 6 and 12 months, improvement in renal reserve (as assessed by renal biomarkers) at 3, 6 and 12 months, reduction in the frequency of large volume paracentesis at 3, 6 and 12 months and change in immune parameters at 3 and 6 months.
详细描述
Study Design Aim & Objectives Primary
• To study the efficacy of targeted albumin therapy versus standard medical treatment in reduction in 6-month mortality in recurrent ascites in patients with decompensated cirrhosis
Secondary Objectives
- To study the frequency of therapeutic paracentesis in both groups
- Incidence of complications: paracentesis induced circulatory dysfunction (PICD), AKI, hyponatremia, bacterial infections, hepatic encephalopathy and variceal bleed
- Impact on systemic hemodynamics and portal pressures
- Impact on fraility and sarcopenia
- Time to resolution of ascites in both groups
- Changes in renal reserve as assessed by sequential Cystatin C based equations for eGFR and other biomarkers (urine-NGAL, Kidney Injury molecule-1, Liver-Fatty Acid Binding Protein (L-FABP) every 3 months)
- Adverse effects and discontinuation rates of beta-blockers in both groups
- Survival free of liver transplant and TIPS in both groups at 6 months and 1 year
- Quality of Life as assessed by short form survey-36 version (SF-36)
- Effect of albumin therapy on immunomodulation
- Effect of albumin on 12-month mortality
Methodology DOSING REGIMEN (Describe the subject or animal dosing) In this open labeled randomized study, consecutive cirrhotic patients, fulfilling the inclusion criteria and exclusion criteria will be enrolled in the study. Details of sample size calculation are given under section of statistical methods. Severity of liver disease will be assessed according to severity scores- CTP and MELD score.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with cirrhosis of liver with recurrent ascites.
- •Patients with age from 18-70 years
排除标准
- •Renal failure (Creatinine >1.5mg/dl)
- •Recent Gastrointestinal bleeding within 7 days
- •Spontaneous bacterial Peritonitis
- •Patients with organic nephropathy ( as defined by IAC)
- •Patients with Cardiovascular disease or chronic obstructive pulmonary disease
- •Systemic arterial hypertension (>160/90mmhg)
- •Presence of hepatocellular carcinoma (outside Milan criteria)( or portal vein thrombosis
- •Budd-Chiari Syndrome
- •Patients with active sepsis
- •Patients with hepatic encephalopathy
- •No use of drugs affecting systemic hemodynamics 7 days prior to enrolment (except beta-blockers)
- •Patients with serum albumin >3 gm
- •Refusal to participate
- •Known or suspected hypersensitivity to albumin
- •Post liver or kidney transplantation
- •Patients enrolled in other clinical trials
- •Extrahepatic malignancy
研究组 & 干预措施
Standard Medical Treatment
Standard Medical Treatment- Salt-restriction, diuretics with large volume paracentesis These patients will be put on low sodium diet (2 g/day) and will be given a combination of loop diuretic (furosemide 40-160 mg/day) and a distal acting diuretic (spironolactone 100-400 mg/day) with dose escalation by one step at a time with monitoring for side-effects. Large volume paracentesis (LVP) will be performed along with intravenous albumin (8 g/L ascites removed) as required with record of the frequency of taps.
Follow up: 2 week, 4 weeks then every 3 months for 1 year
干预措施: Standard Medical Treatment (Drug)
Targeted Albumin with Standard Medical Treatment
Patients with serum albumin <3 g/L with recurrent ascites - Will receive 20 % albumin at 60 grams/week until target serum albumin of 3.0 g/L is achieved following this patients would get 40 grams of albumin every week until ascites resolution or serum albumin >3.5 g/L. Patients who achieve this target will continue with 20 gm/week until patient has complete resolution of ascites and serum albumin >3.5 gm/L this patients would receive albumin 20 gms once every 2 weeks
干预措施: Albumin (Biological)
Targeted Albumin with Standard Medical Treatment
Patients with serum albumin <3 g/L with recurrent ascites - Will receive 20 % albumin at 60 grams/week until target serum albumin of 3.0 g/L is achieved following this patients would get 40 grams of albumin every week until ascites resolution or serum albumin >3.5 g/L. Patients who achieve this target will continue with 20 gm/week until patient has complete resolution of ascites and serum albumin >3.5 gm/L this patients would receive albumin 20 gms once every 2 weeks
干预措施: Standard Medical Treatment (Drug)
结局指标
主要结局
Mortality in both groups
时间窗: 6 months
次要结局
- Change in the frequency of large volume paracentesis in both groups(12 months)
- Survival free of liver transplant in both groups(12 months)
- Change in renal reserve (as assessed by renal biomarkers) in both groups(12 months)
- Number of patients underwent TIPS (Transjugular Intrahepatic Portosystemic Shunt) in both groups(12 months)
- Change in quality of Life as assessed by short form survey-36 version (SF-36) in both groups(12 months)
- Improvement in pro inflammatory cytokines(6 months)
- Mortality in both groups(12 months)
- Incidence of liver-related complications in both groups(12 months)