Treatment of Severe Alcoholic Hepatitis With Corticoids Plus N Acetyl Cysteine Versus Corticoids Alone (HAA-NAC)

Centre Hospitalier Universitaire, Amiens

Status and phase: Completed; Phase 3

Conditions: Alcoholic Hepatitis

Treatments: Drug: Corticoids plus N Acetyl Cysteine

Study type: Interventional

Funder types: Other

Identifiers

NCT00863785

PHRC R04 - Dr NGUYEN-KHAC

AFSSAPS 040276

Details and patient eligibility

About

35% of Acute Alcoholic Hepatitis patients (AAH) do not respond to corticoids and died after 6 months. Chronic alcohol abuse depletes glutathione in the hepatocytes and makes the latter more sensitive to excessive TNFα levels. Re-establishment of a stock of antioxidants by administration of a precursor (N-acetyl cysteine, NAC) in combination with corticoids (C) could make the hepatocytes more resistant and improve survival. The investigators' study's primary endpoint was improvement of survival at 6 months. The secondary endpoints were survival at 1 and 3 months, tolerance of NAC and a drop in blood bilirubin levels at D7

Full description

AAH patients (Maddrey score > 32 and compatible histological results) should centrally randomized into the C-NAC or C groups. Both groups received 4 weeks of prednisolone treatment, plus NAC for the combination therapy group (D1: 150, 50 and 100 mg/kg in 250, 500 and 1000 mL of 5% glucose-saline (G5%) respectively, at t=30 minutes, 4 and 16 hours; D2 to D5, 100 mg/kg in 1000 mL of G5%). Group C received 1000 mL of G5%, D1-5

Enrollment: 174 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patient consent
• Chronic alcohol intake in the last 3 to 6 months
• Maddrey score ≥ 32
• Liver histology compatible

Exclusion criteria

• Hepato renal syndrome
• Hepatocarcinoma
• Recent variceal haemorrhage
• Recent bacterial infections
• Other liver diseases associated (HCV, HBV, hemochromatosis, AIH)
• Cancers or cardiac and respiratory, HIV infection
• NAC Allergy
• No patient consent
• Acetaminophen intoxication

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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174 participants in 1 patient group

Corticoids plus N Acetyl Cysteine

Experimental group

Description:

40 mg/d prednisolone N Acetyl Cysteine infusion 150mg/kg in 30 minutes then 50 mg/kg in 4 h then 100mg/kg in 16 h and finally 100mg/d2 to d5

Treatment:

Drug: Corticoids plus N Acetyl Cysteine