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

Alcoholic Hepatitis Clinical Trial

— HAA-NAC  

Official title:

Treatment of Acute Severe Alcoholic Hepatitis With Corticoids Plus N Acetyl Cysteine Versus Corticoids Alone: a French Multicentre Randomized Controlled Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00863785
• Other study ID #: PHRC R04 - Dr NGUYEN-KHAC
• Secondary ID: AFSSAPS 040276
• Status: Completed
• Phase: Phase 3
• First received: March 17, 2009
• Last updated: October 19, 2009
• Start date: April 2004
• Est. completion date: September 2009

Study information

• Verified date: October 2009
• Source: Centre Hospitalier Universitaire, Amiens
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 174
• Est. completion date: September 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alcoholic Hepatitis
• Hepatitis
• Hepatitis A
• Hepatitis, Alcoholic

Intervention

Drug:
• 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

Locations

Country	Name	City	State
France	Centre Hospitalier d'Abbeville	Abbeville
France	Centre Hospitalier Beauvais	Beauvais
France	Centre Hospitalier Universitaire de Besançon	Besancon
France	Centre Hospitalier Universitaire de Caen	Caen
France	Centre Hospitalier de Cambrai	Cambrai
France	Centre Hospitalier de Compiègne	Compiegne
France	Centre Hospitalier de Lens	Lens
France	Centre Hospitalier Saint-Antoine	Paris
France	Centre Hospitalier Universitaire Pitié-Salpétrière	Paris
France	Centre Hospitalier Universitaire de Reims	Reims
France	Centre Hospitalier Universitaire de Rouen	Rouen
France	Centre Hospitalier de Saint-Quentin	Saint-quentin
France	Centre Hospitalier de Valenciennes	Valenciennes

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire, Amiens

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival at one, three and six months		six months	Yes
Secondary	bilirubin decrease at day seven survival at one and three months nac tolerance side effects		one, three and six months	Yes