Goal Directed Ammonia Lowering Therapy in Hyperammonemic ACLF Patients With no Overt HE to Reduce Major Adverse Liver Related Outcomes (GOAL Trial)- A Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Proportion of patients achieving composite endpoint target NH3 level < 79.5 mmol/L (135mcg/dl) and /or Incidence of major adverse liver related outcomes (MALO) (any of AARC III, bacterial infection, overt HE grade or death) at day 7 in two arms.
研究概览
简要总结
SIRS in ACLF exacerbate adverse effects of ammonia - sarcopenia, infections, immune dysfunction, HE and organ dysfunction Persistent or incident hyperammonemia during first week of hospitalization in patients with ACLF is associated with increased risk of organ failure and death. Prospective studies on the efficacy of ammonia lowering therapies on major adverse liver related outcomes (MALO) (any of AARC III, bacterial infection, overt HE grade or death) in hyperammonemic ACLF patients with no overt HE are limited. In this study we aim to to compare the safety and efficacy of ammonia lowering therapy (goal directed lactulose and rifaximin) compared to SMT to prevent major liver related outcomes (MALO) (any of AARC III, bacterial infection, overt HE grade or death) in hyperammonemic ACLF patients with no overt HE.
详细描述
Hypothesis
Goal directed ammonia lowering therapy in hyperammonemic ACLF patients with no overt HE leads to reduced incidence of major adverse liver related outcomes (MALO) (any of AARC III, bacterial infection, overt HE grade or death) at day 7, 28 and day 90.
AIM:- To compare the safety and efficacy of ammonia lowering therapy (goal directed lactulose and rifaximin) compared to SMT to prevent major liver related outcomes (MALO) (any of AARC III, bacterial infection, overt HE grade or death) in hyperammonemic ACLF patients with no overt HE.
Study design:
- A Prospective Randomized Controlled Trial.
- Single Centre.
- Open label.
- Block Randomization will be done , it will be implemented by IWRS method.
- The study will be conducted in Department of Hepatology, ILBS.
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
- •Age 18-70 years
- •ACLF as per APASL criteria (AARC grade I/II)
- •Baseline ammonia levels of ≥135ug/dl or 79.5umol/l
- •Given informed consent
排除标准
- •AARC grade III
- •Confirmed or suspected bacterial infection
- •Extrahepatic organ failure
- •Renal dysfunction lasting for more than 48 hours or need for vasoconstrictors
- •Paralytic ileus
- •Patients with hepatocellular carcinoma beyond Milan criteria or any other neoplastic disorder
- •Pregnant and lactating women
- •Use of lactulose, rifaximin or LOLA in past 48h
- •Uncontrolled DM, HT, CAD
- •Patients with allergy or other contraindications of the used drugs
研究组 & 干预措施
lactulose and rifaximin
T. Rifaximin 550 mg po bd Syp Lactulose to ensure 2-3 motions
干预措施: Lactulose (Drug)
lactulose and rifaximin
T. Rifaximin 550 mg po bd Syp Lactulose to ensure 2-3 motions
干预措施: Rifaximin (Drug)
Standard Medical Treatment
Routine medicines, Albumin Iv antibiotics,Protein powder , branched chain amino acids
干预措施: Standard Medical treatment (Other)
结局指标
主要结局
Proportion of patients achieving composite endpoint target NH3 level < 79.5 mmol/L (135mcg/dl) and /or Incidence of major adverse liver related outcomes (MALO) (any of AARC III, bacterial infection, overt HE grade or death) at day 7 in two arms.
时间窗: Day 7
次要结局
- Incidence of bacterial infection at day 4 and 7 in two arms(day 4 and 7)
- Incidence of overt HE at day 4 and 7 in two arms(day 4 and 7)
- Proportion of patients with AARC III ACLF at day 4 and 7 in two arms(day 4 and 7)
- Incidence of new AKI, SBP, Variceal bleed at day 4 and 7 in two arms(day 4 and 7)
- Proportion of patients with ammonia <79.5 mmol/L(135mcg/dl) at day 1,2,3 and day 7 in 2 arms(day 1,2,3 and day 7)
- Proportion of patients with >25% and 50% ammonia reduction at day 1,2,3 and day 7 in 2 arms(day 1,2,3 and day 7)
- Liver related mortality at day 28 and day 90(day 28 and day 90)
- Changes in markers of systemic inflammation from baseline and day 7 in two arms(day 7)
- Adverse effect of ammonia lowering therapies(day 90)