Efficacy of Combination Therapy of Glucocorticoids, and Bovine Colostrum in Treatment of Severe Alcoholic Hepatitis: A Pilot Study.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Change in mDf Value from baseline to 8 weeks
研究概览
简要总结
Severe Alcoholic hepatitis (SAH), defined by modified Maddrey's Discriminant Function (DF) ≥32, is associated with significant morbidity and mortality. Of the various treatment modalities evaluated for treatment of SAH, corticosteroids have been the most extensively studied. Five out of 13 RCTs, and four out of 5 meta-analysis have shown a survival benefit with corticosteroids, especially in patients with DF ≥32 and/ or encephalopathy.However, the role of corticosteroids in SAH still remains somewhat controversial. Corticosteroid therapy is not considered the ideal option by all authors because their beneficial effect seems to be confined to a highly selected minority group in which the inhibitory effect of corticosteroids on liver inflammation is not outweighed by side effects such as weakened defence against infections, anti-anabolic effects, and possible ulcer promoting effects. Also corticosteroids are contraindicated in patients with renal failure, gastro-intestinal (GI) bleed, pancreatitis and active sepsis. Therefore, there have been constant efforts to evaluate new therapies for SAH. In a recent trial, combination of glucocorticoids plus N-acetylcysteine was found to improve one month survival in patients with SAH, compared with glucocorticoids alone. However the 6 month survival was not different in both groups.
Human Colostrum (HC) and Bovine Colostrum (BC) are rich in protein, immunoglobulin, lactoferrin and growth factors. Recent studies suggest that colostrum components, Lactroferrin, immunoglobulin and growth factor benefits physically active person and in treatment of autoimmune disorders. It is used for the treatment of a wide variety of gastrointestinal conditions, including non-steroidal anti-inflammatory drug-induced gut injury, H pylori infection, immune deficiency related diarrhea as well as infective diarrhea.
The guidelines by American College of Gastroenterology and other authors have suggested that a combination of CS and other drugs, which have different mechanisms of action, may be more beneficial for reducing mortality in SAH. Hence, we plan to conduct this pilot study to investigate the efficacy of a novel combination of corticosteroids, and Bovine colostrum in the treatment of SAH.
详细描述
Severe alcoholic hepatitis is associated with significant morbidity and mortality.
Diagnosis: The diagnosis of (AH) is made by the following criteria11
I.Chronic active alcohol abuse - > 80 grams in males and > 20 grams in females. II. Duration of jaundice < 3 months III. Serum Bilirubin >5 mg/dl IV. AST/ALT > 2:1 V. AST <500 IU/L, ALT <300 IU/L VI. Neutrophilic leucocytosis VII. Alcohol - non - alcohol index (ANI) determines the aetiology in an obese patient who drinks excessively. The ANI uses body mass index, mean corpuscular volume (MCV), AST/ALT ratio and gender to determine whether the aetiology is alcoholic steatohepatitis or non-alcoholic steatohepatitis (NASH). A high MCV, AST/ALT ratio > 1, low BMI and male gender favours alcohol as the aetiology, and this is reflected as a positive ANI score. A negative score implicates NASH as the cause of liver disease. The ANI calculator is available online (http://www.mayoclinic.org/girst/mayomodel10.html) VIII. Ethyl Glucuronide in urine12 detects alcohol intake within the last 3 days IX. Ethyl Glucuronide in hair13 detects intake of alcohol within the last few months X. Serum Enzyme linked immunosorbent Ethyl Glucuronide has a sensitivity and specificity of 92% and 91% respectively XI. Liver biopsy is useful when the diagnosis is uncertain and when corticosteroids are to be given for the treatment of SAH. A Transjugular liver biopsy is performed in most patients due to the coagulopathy in SAH.
Assessment of Severity Maddrey's Discriminant Function14 Discriminant Function Index (DFI) was originally described by Maddrey and colleagues in a placebo controlled study to assess the benefit of corticosteroids in patients with AH. The original formula was 4.6 x prothrombin time (PT) (seconds) + serum Bilirubin (mg/dl). It was observed that patients with a DFI >93 and treated with placebo had a 28 day survival of 25%, whereas those with a DFI < 93 had a 100% survival. Subsequently this score was modified in 19896 and called Modified Discriminant Function (MDF). MDF = 4.6 x (Patient's PT - Control PT) + serum bilirubin (mg/dl). Untreated patients with MDF >32 had a survival of 68%. The American College of Gastroenterology9 recommends that patients with MDF > 32 and / or Encephalopathy (SAH) be treated with Corticosteroids. The prothrombin time varies greatly depending on the sensitivity of the thromboplastin reagent used for the test. This is the drawback of the MDF.
MELD score15 The model for end stage liver disease (MELD) score predicts survival in patients with cirrhosis and is used to prioritize patients for liver transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Severe Alcoholic hepatitis (mDF > 54)
- •Age 18-65 Year
- •Actively consuming alcohol within 6 weeks of entry into the study
排除标准
- •Failure to obtain informed consent
- •Active infection or sepsis
- •Other concomitant causes of liver disease: viral hepatitis, autoimmune liver disease, metabolic liver disease, vascular liver disease
- •HIV positive
- •Cow milk allergy or severe lactose intolerance
- •Active Gastrointestinal bleeding
- •Acute kidney injury at time of randomization with Creatinine > 1.5 mg/dL
- •Evidence of acute pancreatitis or biliary obstruction
- •Subjects who are pregnant or lactating
- •Significant systemic cardio-pulmonary illness
- •Patients requiring the use of vasopressors or inotropic support in 12 hours prior to randomization
- •Treatment for alcoholic hepatitis within 1 month of study entry with corticosteroids use>1 week.
- •Any patient who has received any investigational drug or device within 30 days entering into the study
结局指标
主要结局
Change in mDf Value from baseline to 8 weeks
时间窗: 2 month
次要结局
- Cytokines Levels (αTNF, IL 6, IL 8) from baseline to 8 weeks.(2 month)
- Change in Endotoxin level from baseline to 8 weeks(2 month)
研究者
Prof. Sandeep S Sidhu
Prof. Sandeep S sidhu
Dayanand Medical College and Hospital