Utility of the Use of N-acetylcysteine Associated With Conventional Treatment in Patients With Severe Acute Alcoholic Hepatitis (Maddrey> 32)

Study Overview
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Brief Summary
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This study is designed to evaluate the hypothesis that patients with severe acute alcoholic hepatitis have lower morbi-mortality if the patients receive treatment with corticosteroids + NAC, compared to patients that only receive corticosteroids.

Detailed Description
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Currently there are no drugs available to cure patients with acute alcoholic hepatitis. The only treatment available is corticosteroids, the efficacy of which is limited and not free of side effects. Other drugs that can contribute to improve the situation of patients with this entity is N-acetylcysteine (NAC), however, in the different studies contradictory data are obtained, therefore, different societies recommend conducting studies of greater scope to confirm the effectiveness of N-acetylcysteine and to be able to make a clear indication about N-acetylcysteines use. Clinical, randomized, controlled, multicenter, parallel and open trial.

Official Title
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Utility of the Use of N-acetylcysteine Associated With Conventional Treatment in Patients With Severe Acute Alcoholic Hepatitis (Maddrey> 32)

Conditions
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Alcoholic Hepatitis

Intervention / Treatment
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* Drug: N-acetylcysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women. Age from 18 to 75 years. Patients with acute alcoholic hepatitis according to AASLD criteria or compatible liver histology. Maddrey score> = 32. Acceptance of participation through written informed consent. Exclusion Criteria: Any cause of jaundice: acute hepatitis, positive HIV serology, biliary-pancreatic pathology, hemolytic anemia. Allergy or intolerance to N-acetylcysteine and / or corticosteroids. Hepatocarcinoma. Portal cavernomatosis. Portal cavernomatosis. Any disease whose life expectancy is less than 12 months. Patients with nitroglycerin and / or carbamazepine-based treatments. Patients with uncontrolled active infection. Acute kidney disease with creatinine> 2.5 mg / dL. Uncontrolled upper gastrointestinal bleeding. Concomitant uncontrolled diseases (HBV, HCV, HIV, TB, DILI, HCC or acute pancreatitis). Multiple organ failure or shock.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Clinical, randomized, controlled, multicenter, parallel and open trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Corticosteroids<br>Corticosteroids following Standard Clinical Practice | Drug: N-acetylcysteine<br>* Day 1: 150 mg/kg in 250ml 5% glucose over 30min + 50mgr/kg in 500ml glucose over 4h + 100mgr/kg in 1000ml glucose over 16h intravenously. Day 2-14: 100mgr/kg in 1000 ml glucose/24h intravenously. Day 15 until end of corticosteroid treatment: NAC 600mg orally every 24h.<br>|
| Experimental: Corticosteroids + N-acetylcysteine<br>Corticosteroids following Standard Clinical Practice plus N-acetylcisteine | Drug: N-acetylcysteine<br>* Day 1: 150 mg/kg in 250ml 5% glucose over 30min + 50mgr/kg in 500ml glucose over 4h + 100mgr/kg in 1000ml glucose over 16h intravenously. Day 2-14: 100mgr/kg in 1000 ml glucose/24h intravenously. Day 15 until end of corticosteroid treatment: NAC 600mg orally every 24h.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with all-cause mortality at 6 months. | Main result variable. | 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with complications: infections, ascites, gastrointestinal bleeding, renal failure, hepatic encephalopathy, need for MARSH or orthotopic liver transplantation. | Security variable. | 3 months |