N-ACetylcysteine to Reduce Infection and Mortality for Alcoholic Hepatitis

Study Overview
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Brief Summary
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Recent data have suggested that monocyte oxidative burst defect is associated with the development of infection in patients with severe alcoholic hepatitis. One report found reduced 28 day mortality in patients treated with N-acetylcysteine combined with prednisolone when compared to prednisolone alone. The current study seeks to reveal whether the mechanism by which NAC reduces susceptibility to infection is through improvement of phagocyte oxidative burst.

Detailed Description
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Randomised controlled trial, open label.

Official Title
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The Mechanism of Action of N-acetylcysteine for Reducing the Risk of Infection in Alcoholic Hepatitis

Conditions
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Alcoholic Hepatitis, Infection

Intervention / Treatment
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* Drug: N-acetyl cysteine (NAC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older Clinical alcoholic hepatitis: Serum bilirubin >80umol/L History of alcohol excess (>80g/day male, >60g/day female) Less than 4 weeks since admission to hospital Maddrey's discriminant function (DF) >32 Informed consent Exclusion Criteria: Alcohol abstinence of >6 weeks prior to randomisation Duration of jaundice >3 months Other causes of liver disease including: Evidence of viral hepatitis (hepatitis B or C) Biliary obstruction Hepatocellular carcinoma Evidence of current malignancy (except non-melanotic skin cancer) Previous entry into the study Patients with known hypersensitivity or previous reactions to NAC Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: prednisolone+NAC<br>40mg prednisolone once a day for 28 days and 30 minutes of intravenous NAC at 150mg/kg in 250ml 5% dextrose solution followed by 4 hours of intravenous NAC at 50mg/kg in 500ml 5% dextrose solution, followed by 16 hours of intravenous NAC at 100 mg/kg in 1000ml 5% dextrose solution, followed by 4 days of intravenous NAC at 100mg/kg/day in 1000ml 5% dextrose solution | Drug: N-acetyl cysteine (NAC)<br> <br> * Other names: NAC;|
| No Intervention: prednisolone<br>40mg prednisolone for 28 days | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in monocyte oxidative burst |  | 24 hours | 
| Improvement in ex vivo monocyte oxidative burst |  | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients infected | Infection will be defined in two ways: i. by new/change in intravenous antibiotic prescription and ii. published clinical and microbiological criteria for infection in the setting of liver disease | 28 days | 
| Proportion of patients infected | Infection will be defined in two ways: i. by new/change in intravenous antibiotic prescription and ii. published clinical and microbiological criteria for infection in the setting of liver disease | 90 days | 
| Death |  | 28 days | 
| Death |  | 90 days |