Clinical trial NCT00863785: Treatment of Severe Alcoholic Hepatitis With Corticoids Plus N Acetyl Cysteine Versus Corticoids Alone
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alcoholic Hepatitis
Keywords: Acute Alcoholic Hepatitis
Cirrhosis
Alcohol
Alcoholic Liver disease
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
First posted: 2009-03-18
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Survival at one, three and six months
timeFrame: six months
Secondary outcomes:
measure: bilirubin decrease at day seven survival at one and three months nac tolerance side effects
timeFrame: one, three and six months
Other outcomes:
Locations:
city: Abbeville
country: France
facility: Centre Hospitalier d'Abbeville
city: Beauvais
country: France
facility: Centre Hospitalier Beauvais
city: Besancon
country: France
facility: Centre Hospitalier Universitaire de Besançon
city: Caen
country: France
facility: Centre Hospitalier Universitaire de Caen
city: Cambrai
country: France
facility: Centre Hospitalier de Cambrai
city: Compiegne
country: France
facility: Centre Hospitalier de Compiègne
city: Lens
country: France
facility: Centre Hospitalier de Lens
city: Paris
country: France
facility: Centre Hospitalier Saint-Antoine
city: Paris
country: France
facility: Centre Hospitalier Universitaire Pitié-Salpétrière
city: Reims
country: France
facility: Centre Hospitalier Universitaire de Reims
city: Rouen
country: France
facility: Centre Hospitalier Universitaire de Rouen
city: Saint-quentin
country: France
facility: Centre Hospitalier de Saint-Quentin
city: Valenciennes
country: France
facility: Centre Hospitalier de Valenciennes
Study officials:
affiliation: Centre Hospitalier Universitaire, Amiens
name: Phillippe DOMY
role: STUDY_DIRECTOR
References:
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.