Intensive Enteral Nutrition and Acute Alcoholic Hepatitis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Christophe MORENO, Erasme University Hospital
ClinicalTrials.gov Identifier:
NCT01801332
First received: February 27, 2013
Last updated: NA
Last verified: February 2013
History: No changes posted
  Purpose

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


Condition Intervention
Severe Alcoholic Hepatitis
Dietary Supplement: intensive nutrition
Dietary Supplement: usual meals

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intensive Enteral Nutrition in Association With Corticosteroids in Severe Acute Alcoholic Hepatitis: a Multicenter, Randomized, Controlled Trial

Resource links provided by NLM:


Further study details as provided by Erasme University Hospital:

Primary Outcome Measures:
  • survival [ Time Frame: 6 months survival ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • survival [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • infection rate during hospitalisation, early bilirubin change (day 7), Lille score, development of hepatorenal syndrome [ Time Frame: entire study duration (6 months) ] [ Designated as safety issue: Yes ]

Enrollment: 136
Study Start Date: February 2010
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: intensive arm
Corticosteroïds (Methylprednisolone 32 mg/d) for 28 days + intensive enteral nutrition by feeding tube for 14 days
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.
Active Comparator: control arm
Corticosteroïds (Methylprednisolone 32 mg/d) for 28 days + " classical " oral alimentation for 14 days
Dietary Supplement: 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.

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01801332

Locations
Belgium
UZ Antwerpen
Antwerp, Belgium
AZ Brugge
Brugge, Belgium
CHU Saint-Pierre
Brussels, Belgium, 1000
AZ VUB
Brussels, Belgium, 1090
Hôpitaux Iris-Sud
Brussels, Belgium
CHU Brugmann
Brussels, Belgium, 1020
Cliniques universitaires Saint-Luc
Brussels, Belgium
Erasme University Hospital
Brussels, Belgium, 1070
UZ Gent
Gent, Belgium
Hôpital de Jolimont
La Louvière, Belgium
KU Leuven
Leuven, Belgium
ULG Sart Tilman
Liège, Belgium
Hôpital Saint-Joseph
Liège, Belgium
CHR La Citadelle
Liège, Belgium
CHR Saint Joseph-Warquignies
Mons, Belgium
Hôpital Ambroise Paré
Mons, Belgium
Hôpital Ottignies
Ottignies-Louvain-La-Neuve, Belgium
France
CHU Caen
Caen, France
CHU Lille
Lille, France
Sponsors and Collaborators
Erasme University Hospital
Investigators
Principal Investigator: Christophe Moreno, MD, PhD Erasme University Hospital
  More Information

No publications provided

Responsible Party: Christophe MORENO, Clinical director of the liver unit, Department of Gastroenterology, Hepatopancreatology and Digestive oncology, Erasme University Hospital
ClinicalTrials.gov Identifier: NCT01801332     History of Changes
Other Study ID Numbers: NETI HAA
Study First Received: February 27, 2013
Last Updated: February 27, 2013
Health Authority: Belgium: Ethics Committee
Belgium: Belgian Association for the study of the liver

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Chemically-Induced Disorders
Digestive System Diseases
Enterovirus Infections
Hepatitis, Viral, Human
Liver Diseases
Liver Diseases, Alcoholic
Picornaviridae Infections
RNA Virus Infections
Substance-Related Disorders
Virus Diseases

ClinicalTrials.gov processed this record on October 21, 2014