Treatment of Severe Alcoholic Hepatitis With Corticoids Plus N Acetyl Cysteine Versus Corticoids Alone

Phase 3

Completed

• Conditions: Alcoholic Hepatitis
• Interventions: Drug: Corticoids plus N Acetyl Cysteine

• Registration Number: NCT00863785
• Lead Sponsor: Centre Hospitalier Universitaire, Amiens

Brief Summary

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

Detailed 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

Study Timeline

• Study Start: 2004-04
• Study First Submitted: 2009-03-17
• Study First Submitted QC: 2009-03-17
• Study First Posted: 2009-03-18
• Primary Completion: 2009-08
• Study Completion: 2009-09
• Status Verified: 2009-10
• Last Update Submitted: 2009-10-19
• Last Update Posted: 2009-10-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 174

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Corticoids plus N Acetyl Cysteine	Corticoids plus N Acetyl Cysteine	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

Primary Outcome Measures

Name	Time	Method
Survival at one, three and six months	six months

Secondary Outcome Measures

Name	Time	Method
bilirubin decrease at day seven survival at one and three months nac tolerance side effects	one, three and six months

Trial Locations

Locations (13)

Centre Hospitalier de Compiègne; 🇫🇷 Compiegne, France

Centre Hospitalier d'Abbeville; 🇫🇷 Abbeville, France

Centre Hospitalier Universitaire de Rouen; 🇫🇷 Rouen, France

Centre Hospitalier Saint-Antoine; 🇫🇷 Paris, France

Centre Hospitalier de Cambrai; 🇫🇷 Cambrai, France

Centre Hospitalier Universitaire de Caen; 🇫🇷 Caen, France

Centre Hospitalier de Lens; 🇫🇷 Lens, France

Centre Hospitalier Universitaire de Reims; 🇫🇷 Reims, France

Centre Hospitalier Universitaire Pitié-Salpétrière; 🇫🇷 Paris, France

Centre Hospitalier Beauvais; 🇫🇷 Beauvais, France

Centre Hospitalier Universitaire de Besançon; 🇫🇷 Besancon, France

Centre Hospitalier de Saint-Quentin; 🇫🇷 Saint-quentin, France

Centre Hospitalier de Valenciennes; 🇫🇷 Valenciennes, France