Impact of Double Plasma Separation and Adsorption on Patients With Acute on Chronic Liver Failure- A Prospective Open-label Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 56
- 主要终点
- Improvement in AARC ACLF grade by one at day 14 (after 7 days off treatment)
研究概览
简要总结
Acute-on-chronic liver failure (ACLF) is a serious condition in which patients with chronic liver disease suddenly develop severe liver injury, leading to inflammation, organ failure, and very high short-term mortality. Standard medical treatment can help, but many patients still do poorly without liver transplantation.
This study will test whether Double Plasma Molecular Adsorption System (DPMAS), an extracorporeal blood purification therapy, can improve outcomes in ACLF patients. DPMAS works by filtering the blood through special adsorption columns that remove harmful substances such as bile acids, toxins, and inflammatory molecules.
In this randomized controlled trial, adult patients with ACLF will be randomly assigned to receive either:
Standard medical therapy alone, or
Standard medical therapy plus DPMAS.
The main goal is to see whether DPMAS can improve liver function and reduce disease severity within 14 days. Other outcomes include survival without liver transplant at 28 days, improvement in organ functions, reduction in inflammation, and safety of the procedure.
The study will be conducted at the Institute of Liver and Biliary Sciences (ILBS), New Delhi, India, and will enroll about 56 participants over one year.
详细描述
Acute-on-chronic liver failure (ACLF) is characterized by acute deterioration of liver function in patients with chronic liver disease, leading to systemic inflammation, organ failure, and high short-term mortality. Current treatment is largely supportive, and liver transplantation is often the only curative option, but many patients are not eligible or die while awaiting transplant.
Recent evidence suggests that systemic inflammation, bile acid accumulation, and damage-associated molecular patterns (DAMPs) play key roles in the progression of ACLF. Extracorporeal liver support systems such as plasma exchange have shown benefit in selected patients by reducing inflammation and improving short-term survival.
The Double Plasma Molecular Adsorption System (DPMAS) is a novel extracorporeal therapy that combines plasma separation with sequential adsorption columns. These columns are designed to remove bile acids, bilirubin, cytokines, and other toxins from the circulation. Early studies suggest that DPMAS may improve organ function and reduce mortality in ACLF.
This prospective, open-label, randomized controlled trial will compare standard medical therapy (SMT) alone versus SMT plus DPMAS in adult patients with ACLF (AARC grade II or higher). The primary outcome is an improvement in AARC grade by 1 at day 14 (7 days off treatment). Secondary outcomes include transplant-free survival at 28 days, changes in systemic inflammation, renal and hemodynamic function, bilirubin and bile acid levels, development of infections or new organ failures, and safety of the therapy.
A total of 56 participants will be enrolled and randomized equally into the two study groups. Patients in the intervention arm will undergo a minimum of two DPMAS sessions within the first seven days, with additional sessions as clinically indicated. Participants will be followed for up to 90 days for survival and clinical outcomes.
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
盲法说明
This is an open-label randomized controlled trial. No masking will be performed for participants, care providers, investigators, or outcomes assessors.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ACLF patients of any etiology with systemic inflammatory response syndrome and AARC grade II or more.
排除标准
- •Patients eligible for corticosteroids for severe alcohol-associated hepatitis related ACLF (other than hydrocortisone according to Surviving Sepsis Campaign Guidelines 2021 which is 50 mg iv q 6 h for management of refractory shock
- •Hepatocellular carcinoma or any extrahepatic malignancy,
- •Active fungal sepsis
- •Disseminated intravascular coagulation
- •Hemodynamic instability requiring norepinephrine >0.20ug/kg/min
- •Patients with coma of non-hepatic origin
- •Patients with PaO2/FiO2 ratio <150
- •Pregnancy
- •Comorbidities associated with poor outcomes (severe cardiopulmonary disease defined by a New York Heart Association score >3, or oxygen/steroid-dependent chronic obstructive pulmonary disease, chronic kidney disease) and patients with post-resection liver failure
- •Patients with fibrinogen <110 and/or platelets less than 50,000
- •Patients with oliguria with urine output less than 400 ml/day
- •Lack of informed consent
- •Patient enrolled in other clinical trials
研究组 & 干预措施
Standard Medical Therapy (SMT) Group
Participants will receive standard medical therapy alone, which may include nutritional support, lactulose, bowel wash, albumin, vasopressors (norepinephrine/terlipressin), antibiotics, antivirals for HBV reactivation, renal replacement therapy, and intensive care support as per institutional guidelines.
干预措施: Standard medical therapy (SMT) (Other)
SMT + Double Plasma Molecular Adsorption System (DPMAS)
Participants will receive standard medical therapy plus DPMAS therapy. DPMAS involves extracorporeal liver support using two sequential hemoadsorption cartridges (BS330 ion exchange resin and HA330-II neutral macroporous adsorption resin). A minimum of 2 sessions (3-4 hours each) will be given in the first 7 days, with additional sessions if partial response is observed.
干预措施: Standard medical therapy (SMT) (Other)
SMT + Double Plasma Molecular Adsorption System (DPMAS)
Participants will receive standard medical therapy plus DPMAS therapy. DPMAS involves extracorporeal liver support using two sequential hemoadsorption cartridges (BS330 ion exchange resin and HA330-II neutral macroporous adsorption resin). A minimum of 2 sessions (3-4 hours each) will be given in the first 7 days, with additional sessions if partial response is observed.
干预措施: Double Plasma Molecular Adsorption System (DPMAS) (Device)
结局指标
主要结局
Improvement in AARC ACLF grade by one at day 14 (after 7 days off treatment)
时间窗: 14 days
Proportion of participants who show an improvement of at least one grade in the Asian Pacific Association for the Study of the Liver acute-on-chronic liver failure (AARC ACLF) score at day 14, assessed after a treatment-free interval of 7 days from randomisation.
次要结局
- Transplant-free survival(28 Days)
- Safety and tolerability of DPMAS(Upto 90 days)
- Transplant-free survival(28 Days)
- Incidence of new infections(28 days)
- Development of new organ failures(28 days)
- Change in cytokine levels(14 days)
- Change in vasopressor requirement(14 days)
- Incidence of new infections(28 days)
- Development of new organ failures(28 days)
- Change in DAMPs(14 days)
- Change in serum bilirubin levels(14 days)
- Change in serum bile acid levels(14 days)
- Change in serum creatinine levels(14 days)
- Change in urine output(14 days)
- Change in mean arterial pressure(14 days)
- Safety and tolerability of DPMAS(Upto 90 days)
研究者
Rakhi Maiwall
Professor of hepatology
Institute of Liver and Biliary Sciences, India