Intensive Enteral Nutrition and Acute Alcoholic Hepatitis

Severe Alcoholic Hepatitis Clinical Trial

Official title:

Intensive Enteral Nutrition in Association With Corticosteroids in Severe Acute Alcoholic Hepatitis: a Multicenter, Randomized, Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01801332
• Other study ID #: NETI HAA
• Status: Completed
• Phase: N/A
• First received: February 27, 2013
• Last updated: February 27, 2013
• Start date: February 2010

Study information

• Verified date: February 2013
• Source: Erasme University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Ethics CommitteeBelgium: Belgian Association for the study of the liver
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Dietary Supplement:
• intensive nutrition
Patients randomized in " intensive enteral nutrition " arm will receive by feeding tube (with the use of a microsonde), and in continuous administration, 2 liters of Fresubin HP Energy (1500 kcal/liter, 75 gr prot/liter) for patients with a weight of more than 90 kgs (after ascites removal), 1.5 liters of Fresubin HP Energy for patients with a weight between 60 and 90 kgs, and 1 liter of Fresubin HP Energy for patients of less than 60 kgs. Patients with significant encephalopathy despite therapy against encephalopathy will receive Fresubin Hepa in place of Fresubin HP Energy (1300 kcal/liter, 40 gr prot/liter, 44 % branched AA). Duration of enteral nutrition by feeding tube will be 14 days. The adaptation to the targeted volume must be achieved in maximum 3 days. Enteral nutrition will be administered by nasogastric microsonde.
• usual meals
Patients randomized in " classical oral nutrition " arm (control arm) will receive usual meals (estimated at 1750 kcal/day; 70 g protein/day), and alimentary supplements between meals to achieve the ESPEN recommandations (35-40 kcal/kg/day; protein 1.2-1.5 g/kg/day) (Plauth et al, Clinical Nutrition 2006). Calories and proteins intake must be recorded daily.

Locations

Country	Name	City	State
Belgium	UZ Antwerpen	Antwerp
Belgium	AZ Brugge	Brugge
Belgium	AZ VUB	Brussels
Belgium	CHU Brugmann	Brussels
Belgium	CHU Saint-Pierre	Brussels
Belgium	Cliniques universitaires Saint-Luc	Brussels
Belgium	Erasme University Hospital	Brussels
Belgium	Hôpitaux Iris-Sud	Brussels
Belgium	UZ Gent	Gent
Belgium	Hôpital de Jolimont	La Louvière
Belgium	KU Leuven	Leuven
Belgium	CHR La Citadelle	Liège
Belgium	Hôpital Saint-Joseph	Liège
Belgium	ULG Sart Tilman	Liège
Belgium	CHR Saint Joseph-Warquignies	Mons
Belgium	Hôpital Ambroise Paré	Mons
Belgium	Hôpital Ottignies	Ottignies-Louvain-La-Neuve
France	CHU Caen	Caen
France	CHU Lille	Lille

Sponsors (1)

Lead Sponsor	Collaborator
Erasme University Hospital

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	infection rate during hospitalisation, early bilirubin change (day 7), Lille score, development of hepatorenal syndrome		entire study duration (6 months)	Yes
Primary	survival		6 months survival	No
Secondary	survival		1 month	No