Treatment of Severe Alcoholic Hepatitis With Corticoids Plus N Acetyl Cysteine Versus Corticoids Alone (HAA-NAC)
Primary Purpose
Alcoholic Hepatitis
Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Corticoids plus N Acetyl Cysteine
Sponsored by
About this trial
This is an interventional treatment trial for Alcoholic Hepatitis focused on measuring Acute Alcoholic Hepatitis, Cirrhosis, Alcohol, Alcoholic Liver disease
Eligibility 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
Sites / Locations
- Centre Hospitalier d'Abbeville
- Centre Hospitalier Beauvais
- Centre Hospitalier Universitaire de Besançon
- Centre Hospitalier Universitaire de Caen
- Centre Hospitalier de Cambrai
- Centre Hospitalier de Compiègne
- Centre Hospitalier de Lens
- Centre Hospitalier Saint-Antoine
- Centre Hospitalier Universitaire Pitié-Salpétrière
- Centre Hospitalier Universitaire de Reims
- Centre Hospitalier Universitaire de Rouen
- Centre Hospitalier de Saint-Quentin
- Centre Hospitalier de Valenciennes
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Corticoids plus N Acetyl Cysteine
Arm 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
Outcomes
Primary Outcome Measures
Survival at one, three and six months
Secondary Outcome Measures
bilirubin decrease at day seven survival at one and three months nac tolerance side effects
Full Information
NCT ID
NCT00863785
First Posted
March 17, 2009
Last Updated
October 19, 2009
Sponsor
Centre Hospitalier Universitaire, Amiens
1. Study Identification
Unique Protocol Identification Number
NCT00863785
Brief Title
Treatment of Severe Alcoholic Hepatitis With Corticoids Plus N Acetyl Cysteine Versus Corticoids Alone
Acronym
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.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2009
Overall Recruitment Status
Completed
Study Start Date
April 2004 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
September 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Centre Hospitalier Universitaire, Amiens
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Hepatitis
Keywords
Acute Alcoholic Hepatitis, Cirrhosis, Alcohol, Alcoholic Liver disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
174 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Corticoids plus N Acetyl Cysteine
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
Corticoids plus N Acetyl Cysteine
Other Intervention Name(s)
AAH-NAC study
Intervention 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
Primary Outcome Measure Information:
Title
Survival at one, three and six months
Time Frame
six months
Secondary Outcome Measure Information:
Title
bilirubin decrease at day seven survival at one and three months nac tolerance side effects
Time Frame
one, three and six months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Phillippe DOMY
Organizational Affiliation
Centre Hospitalier Universitaire, Amiens
Official's Role
Study Director
Facility Information:
Facility Name
Centre Hospitalier d'Abbeville
City
Abbeville
Country
France
Facility Name
Centre Hospitalier Beauvais
City
Beauvais
ZIP/Postal Code
60000
Country
France
Facility Name
Centre Hospitalier Universitaire de Besançon
City
Besancon
ZIP/Postal Code
25030
Country
France
Facility Name
Centre Hospitalier Universitaire de Caen
City
Caen
ZIP/Postal Code
14000
Country
France
Facility Name
Centre Hospitalier de Cambrai
City
Cambrai
Country
France
Facility Name
Centre Hospitalier de Compiègne
City
Compiegne
Country
France
Facility Name
Centre Hospitalier de Lens
City
Lens
Country
France
Facility Name
Centre Hospitalier Saint-Antoine
City
Paris
Country
France
Facility Name
Centre Hospitalier Universitaire Pitié-Salpétrière
City
Paris
Country
France
Facility Name
Centre Hospitalier Universitaire de Reims
City
Reims
Country
France
Facility Name
Centre Hospitalier Universitaire de Rouen
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
Centre Hospitalier de Saint-Quentin
City
Saint-quentin
Country
France
Facility Name
Centre Hospitalier de Valenciennes
City
Valenciennes
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
22070475
Citation
Nguyen-Khac E, Thevenot T, Piquet MA, Benferhat S, Goria O, Chatelain D, Tramier B, Dewaele F, Ghrib S, Rudler M, Carbonell N, Tossou H, Bental A, Bernard-Chabert B, Dupas JL; AAH-NAC Study Group. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med. 2011 Nov 10;365(19):1781-9. doi: 10.1056/NEJMoa1101214.
Results Reference
derived
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Treatment of Severe Alcoholic Hepatitis With Corticoids Plus N Acetyl Cysteine Versus Corticoids Alone
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