Intravenous Branched-chain Amino Acids for Overt Hepatic Encephalopathy in Patients With Acute on Chronic Liver Failure - A Multi-centric Double-blind Randomized Controlled Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- Survival
研究概览
简要总结
This multi-centric study analyses the effect of intravenous branched-chain amino acids (BCAA) on overt HE in patients with ACLF. The investigators aim to study the efficacy of combining intravenous BCAA with lactulose versus lactulose alone, ammonia measures, endotoxin, metabolomics, and cerebral edema in the medical management of overt HE in patients with ACLF. The study will also access the impact on overall survival and improvement in the grade of HE.
详细描述
Treatment of HE in ACLF is based on extrapolation of data available from cirrhotic patients with HE. The mainstay of treatment remains Lactulose. Rifaximin is added on to therapy who have a breakthrough episode of HE on lactulose. BCAA is used as an add-on therapy if patients have minimal/covert encephalopathy, are protein intolerant or have recurrent HE. No studies are available assessing the adjuvant effect of intravenous BCAA on ammonia reduction in HE in patients with ACLF. So, this study has been designed to analyze the effect of intravenous BCAA on hepatic encephalopathy in patients with ACLF. This study will also analyze the systemic and neuronal inflammation, metabolomics, and cerebral edema under the effect of intravenous BCAA in HE patients with ACLF.
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)
盲法说明
Double-blind Placebo Controlled
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years
- •Either gender
- •Patients with ACLF (CANONIC definition) of any etiology with HE ≥grade 2 as per West-Haven Criteria
排除标准
- •Those who do not consent to participate in the study
- •Patients with structural brain lesions or stroke
- •Inability to obtain informed consent from patient or relatives
- •Severe preexisting cardiopulmonary disease
- •Renal dysfunction (S. Creatinine ≥ 2mg/dL)
- •Pregnancy/Lactation
- •Post liver transplant patients
- •HIV infection
- •Patients who are on psychoactive drugs, like sedatives or antidepressants
- •Patients who are too sick to carry out the protocol.
研究组 & 干预措施
Experiential Arm
Drug: iv Branch Chain Amino Acid + Lactulose Intravenous Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose
干预措施: Branch Chain Amino Acid (Drug)
Experiential Arm
Drug: iv Branch Chain Amino Acid + Lactulose Intravenous Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose
干预措施: Lactulose (Drug)
Comparator Arm
Drug: Lactulose + Placebo of IV BCAA solution
干预措施: Lactulose (Drug)
结局指标
主要结局
Survival
时间窗: Day 28
Survival assessment will be made by recording all deaths
次要结局
- Improvement of encephalopathy by one or more grade(Day 7)
- Reduction of arterial ammonia Level(Day 7)
- Reduction of consciousness recovery time among survivors(Day 28)
- Assessment of metabolomics following BCAA + Lactulose and Lactulose alone(Day 7)
- Prevention/reduction of cerebral edema based on optic nerve sheath diameter (ONSD)(72 Hours)
- Assessment of cerebral edema(Discharge form Hospital and 3 month of episode of HE)
- Survival(Day 90)
- Dynamic Assessment of systemic inflammation (Cytokines: IL-1b, IL-6, INF-g, TNF-a, IL-15, IL-17, IL-18) at presentation and after Specific management.(Day 0)
研究者
Madhumita Premkumar
ASSOCIATE PROFESSOR
Post Graduate Institute of Medical Education and Research, Chandigarh