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

This study has been completed.
Sponsor:
Information provided by:
Centre Hospitalier Universitaire, Amiens
ClinicalTrials.gov Identifier:
NCT00863785
First received: March 17, 2009
Last updated: October 19, 2009
Last verified: October 2009
  Purpose

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


Condition Intervention Phase
Alcoholic Hepatitis
Drug: Corticoids plus N Acetyl Cysteine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Treatment of Acute Severe Alcoholic Hepatitis With Corticoids Plus N Acetyl Cysteine Versus Corticoids Alone: a French Multicentre Randomized Controlled Study.

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire, Amiens:

Primary Outcome Measures:
  • Survival at one, three and six months [ Time Frame: six months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • bilirubin decrease at day seven survival at one and three months nac tolerance side effects [ Time Frame: one, three and six months ] [ Designated as safety issue: Yes ]

Enrollment: 174
Study Start Date: April 2004
Study Completion Date: September 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
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
Other Name: AAH-NAC study

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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00863785

Locations
France
Centre Hospitalier d'Abbeville
Abbeville, France
Centre Hospitalier Beauvais
Beauvais, France, 60000
Centre Hospitalier Universitaire de Besançon
Besancon, France, 25030
Centre Hospitalier Universitaire de Caen
Caen, France, 14000
Centre Hospitalier de Cambrai
Cambrai, France
Centre Hospitalier de Compiègne
Compiegne, France
Centre Hospitalier de Lens
Lens, France
Centre Hospitalier Universitaire Pitié-Salpétrière
Paris, France
Centre Hospitalier Saint-Antoine
Paris, France
Centre Hospitalier Universitaire de Reims
Reims, France
Centre Hospitalier Universitaire de Rouen
Rouen, France, 76031
Centre Hospitalier de Saint-Quentin
Saint-quentin, France
Centre Hospitalier de Valenciennes
Valenciennes, France
Sponsors and Collaborators
Centre Hospitalier Universitaire, Amiens
Investigators
Study Director: Phillippe DOMY Centre Hospitalier Universitaire, Amiens
  More Information

No publications provided by Centre Hospitalier Universitaire, Amiens

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amiens University Hospital
ClinicalTrials.gov Identifier: NCT00863785     History of Changes
Other Study ID Numbers: PHRC R04 - Dr NGUYEN-KHAC, AFSSAPS 040276
Study First Received: March 17, 2009
Last Updated: October 19, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Hospitalier Universitaire, Amiens:
Acute Alcoholic Hepatitis
Cirrhosis
Alcohol
Alcoholic Liver disease

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Hepatitis
Hepatitis A
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on September 14, 2014