Efficacy of intravenous ‘L-ornithine L-aspartate’ in reversal of overt acute hepatic encephalopathy in patients with liver cirrhosis: a prospective, randomized, double-blind, placebo controlled trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 164
- 试验地点
- 2
- 主要终点
- Mental state grade
研究概览
简要总结
Hepatic encephalopathy (HE) is a potentially reversible functional disorder of the brain with neurological and psychiatric symptoms. HE occurs in up to 70% of patients with cirrhosis at some time during the course of disease. The chief neurotoxin implicated in the development of HE is ammonia. An important aim of treatment of HE is the reduction of the ammonia in the body by lowering the amount of ammonia produced and increasing its detoxification. Enteric production of ammonia can be decreased by non-absorbable disaccharides such as lactulose and antibiotics such as rifaximin. L-ornithine- L-aspartate (LOLA), the salt of the natural amino acids ornithine and aspartate acts through the mechanism of substrate activation to detoxify ammonia. In clinical trials, LOLA has shown a statistically significant effect with respect to reduction in HE grade, reduction of blood ammonia concentration and positive effects on psychomotor function in patients of cirrhosis with minimal HE and overt chronic Grade I HE, as compared to placebo. However, there is lack of data on the efficacy of LOLA in patients with overt acute hepatic encephalopathy which is one of the major causes of hospital admissions and resource utilization in decompensated cirrhotics.Each admission for HE causes a major financial loss to the family and financial burden on the society. Any drug which decreases the hospital stay by rapidly improving HE, will clearly lead to decreased hospital costs to the individual and the society as a whole. Hence, such a trial is a national priority. We hypothesize that LOLA, if added to the standard treatment of overt acute HE (i.e lactulose), may lead to a faster recovery and decrease in hospital stay of these patients. In this prospective, randomized, placebo controlled trial, we aim to evaluate the efficacy of intravenous L-ornithine, L-aspartate in reversal of overt acute hepatic encephalopathy in patients with liver cirrhosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •Hepatic cirrhosis based on clinical, biochemical, radiological and/or histological data.
- •Patients with overt acute grade 2, 3 and 4 HE, according to the West Haven criteria.
- •Age of patient >18 years d.
- •Patients with or without a precipitating factor for the HE.
排除标准
- •a.Patients who are terminally ill (End Stage Liver Disease, MELD more than 15) b.Chronic HE, on Lactulose or antibiotics c.Acute superposed liver injury (hepatitis) or acute on chronic liver failure d.Severe septicemia with shock e.Hepatocellular carcinoma f.
- •Wilson’s disease as the etiological factor of liver disease g.
- •Advanced cardiac or pulmonary disease h.Acute renal failure or end stage renal disease i.Neuro-degenerative disease or major psychiatric illness j.Patients on sedatives or antidepressants k.Pregnancy or breastfeeding.
结局指标
主要结局
Mental state grade
时间窗: 5 days
次要结局
- Blood ammonia levels
- Mortality(4 weeks)
- Hospital stay(4 weeks)