Clinical trial NCT01801332: Intensive Enteral Nutrition and Acute Alcoholic Hepatitis
Official title: Intensive Enteral Nutrition in Association With Corticosteroids in Severe Acute Alcoholic Hepatitis: a Multicenter, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Alcoholic Hepatitis
Lead sponsor: Erasme University Hospital
Sponsor class: OTHER
First posted: 2013-02-28
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the effect of an intensive enteral nutrition (compared to clinical routine) in association with corticosteroïds in patients with severe acute alcoholic hepatitis.

Detailed description: Acute alcoholic hepatitis (AAH) is characterized by hepatocellular necrosis, ballooning degeneration and an inflammatory reaction with many polymorphonuclear leukocytes, and fibrosis (Mezey E. Treatment of alcoholic liver disease. Semin Liver Dis 1993). The presence of a severe AAH was identified by the presence of a discriminant function (DF) ≥ 32. DF ≥ 32 has been shown to prospectively identify patients with a 40 to 50 % risk of dying within 2 months (Ramond et al, NEJM 1992). The main treatment of AAH consists of abstinence from alcohol. Corticosteroids are generally recommended in patients with severe AAH. Indeed, a recent analysis of the individual data of the patients from the last three randomized controlled trials showed a significantly higher 1-month survival in corticosteroids compared to placebo treated patients with a severe AAH (Mathurin et al, J hepatol 2002). However, efficacy of this therapy is insufficient, since around 40 % of patients with a severe AAH do not respond to corticosteroids (Louvet et al, Hepatology 2007). Moreover, corticosteroïds are still contraindicated in case of active infection or gastrointestinal bleeding, which are relatively common complications in those patients. Therefore, alternative therapeutic options are needed and must be a medical priority.

Alcoholic patients with severe AAH are frequently malnourished and usually remain anorectic for several weeks (DiCecco SR et al, Nutr Clin Pract 2006). Some data indicate that malnutrition is a factor of bad prognosis in this disease. Recent evidence was also provided that adequate enteral nutritional support might have an important impact on long-term survival in those patients (Cabré et al, Hepatology 2000). However, up to now, no study evaluated potential synergetic effect of intensive enteral nutrition and corticosteroids. Moreover, in clinical practice, in the majority of the centers, patients with alcoholic hepatitis receive alimentary supplements and dietetic counseling, which is often insufficient and difficult to apply and to follow.

Aim :

To evaluate the effect of an intensive enteral nutrition (compared to clinical routine which consists in oral supplements) in association with corticosteroïds in patients with severe acute alcoholic hepatitis.

Eligibility criteria: Inclusion Criteria:

* Acute alcoholic hepatitis proven by a liver biopsy (necessary histological findings : neutrophils infiltration, ballooned hepatocytes and Mallory bodies)
* Presence of a severe disease, defined by a Maddrey score higher than or equal to 32, at screening and in baseline (day 0). Maddrey score = total bilirubin in mg/dl + 4,6 X (Prothrombin time patient in sec - prothrombin time control in sec)
* Age between 18 and 75 years old, extremes included
* Recent jaundice or in recent aggravation (less than 3 months)
* Chronic alcohol consumption (more than 40 g/day)
* Informed consent read, understand and signed by the patient (in case of significant encephalopathy, a family representative can signed in place of the patient)
* Maximal delay between admission and randomization of 14 days.

Exclusion Criteria:

* Other disease compromising 6 months survival of the patient
* Positive HIV or HCV serology, positive HBs Antigen
* Uncontrolled bacterial or fungal infection (infection must be judged controlled for at least 3 days)
* Uncontrolled upper GI bleeding (bleeding must be controlled for at least 5 days)
* Type 1 Hepatorenal syndrome (creatinin upper than 2,5 mg/dl), as defined by Salerno F et al, Gut 2007;56:1310-1318
* History of bariatric surgery
* Pentoxyphilline therapy
* MARS therapy

Primary outcomes:
measure: survival
timeFrame: 6 months survival
Secondary outcomes:
measure: survival
timeFrame: 1 month
Other outcomes:
measure: infection rate during hospitalisation, early bilirubin change (day 7), Lille score, development of hepatorenal syndrome
timeFrame: entire study duration (6 months)
Locations:
city: Antwerp
country: Belgium
facility: UZ Antwerpen
city: Brugge
country: Belgium
facility: AZ Brugge
city: Brussels
country: Belgium
facility: CHU Saint-Pierre
city: Brussels
country: Belgium
facility: CHU Brugmann
city: Brussels
country: Belgium
facility: Erasme University Hospital
city: Brussels
country: Belgium
facility: AZ VUB
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Brussels
country: Belgium
facility: Hôpitaux Iris-Sud
city: Gent
country: Belgium
facility: UZ Gent
city: La Louvière
country: Belgium
facility: Hôpital de Jolimont
city: Leuven
country: Belgium
facility: KU Leuven
city: Liège
country: Belgium
facility: CHR La Citadelle
city: Liège
country: Belgium
facility: Hôpital Saint-Joseph
city: Liège
country: Belgium
facility: ULG Sart Tilman
city: Mons
country: Belgium
facility: CHR Saint Joseph-Warquignies
city: Mons
country: Belgium
facility: Hôpital Ambroise Paré
city: Ottignies-Louvain-La-Neuve
country: Belgium
facility: Hôpital Ottignies
city: Caen
country: France
facility: CHU Caen
city: Lille
country: France
facility: CHU Lille
Study officials:
affiliation: Erasme University Hospital
name: Christophe Moreno, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moreno C, Deltenre P, Senterre C, Louvet A, Gustot T, Bastens B, Hittelet A, Piquet MA, Laleman W, Orlent H, Lasser L, Serste T, Starkel P, De Koninck X, Negrin Dastis S, Delwaide J, Colle I, de Galocsy C, Francque S, Langlet P, Putzeys V, Reynaert H, Degre D, Trepo E. Intensive Enteral Nutrition Is Ineffective for Patients With Severe Alcoholic Hepatitis Treated With Corticosteroids. Gastroenterology. 2016 Apr;150(4):903-10.e8. doi: 10.1053/j.gastro.2015.12.038. Epub 2016 Jan 5.