Severe Alcoholic HepatitisNCT01801332
Intensive Enteral Nutrition and Acute Alcoholic Hepatitis
A study testing intensive nutrition and usual meals in people with Severe Alcoholic Hepatitis, run by Erasme University Hospital at 19 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Severe Alcoholic Hepatitis
- What is being tested?
- intensive nutrition and usual meals
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 136 participants
- Where
- 19 sitesin 2 countries
- Study dates
- Feb 2010to Feb 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
19 sites in 2 countries.
19 sites in 2 countries
Belgium17 sites
UZ Antwerpen
Antwerp
AZ Brugge
Bruges
CHU Saint-Pierre
Brussels, 1000
CHU Brugmann
Brussels, 1020
Erasme University Hospital
Brussels, 1070
AZ VUB
Brussels, 1090
Cliniques universitaires Saint-Luc
Brussels
Hôpitaux Iris-Sud
Brussels
UZ Gent
Ghent
Hôpital de Jolimont
La Louvière
KU Leuven
Leuven
CHR La Citadelle
Liège
Hôpital Saint-Joseph
Liège
ULG Sart Tilman
Liège
CHR Saint Joseph-Warquignies
Mons
Hôpital Ambroise Paré
Mons
Hôpital Ottignies
Ottignies-Louvain-la-Neuve
About this study
Official title: Intensive Enteral Nutrition in Association With Corticosteroids in Severe Acute Alcoholic Hepatitis: a Multicenter, Randomized, Controlled Trial
To evaluate the effect of an intensive enteral nutrition (compared to clinical routine) in association with corticosteroïds in patients with severe acute alcoholic hepatitis.
Read the 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.
- Conditions
- Severe Alcoholic Hepatitis
- Being tested
- intensive nutrition, usual meals
- Medical subject headings
- Hepatitis, Alcoholic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intensive nutritionDietary supplement
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 mealsDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| intensive arm | Experimental | Corticosteroïds (Methylprednisolone 32 mg/d) for 28 days + intensive enteral nutrition by feeding tube for 14 days Receives: Dietary Supplement: intensive nutrition |
| control arm | Active comparator | Corticosteroïds (Methylprednisolone 32 mg/d) for 28 days + " classical " oral alimentation for 14 days Receives: Dietary Supplement: usual meals |
What is being measured
The primary outcome is the main question the study is designed to answer.
survival
Measured: 6 months survival
Secondary outcomes (1)
survival
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2013 (estimated)
- Study startFeb 2010
- Primary completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe Alcoholic HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 136 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasme University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christophe MORENO, Erasme University Hospital
- Investigators
- Christophe Moreno, MD, PhD, Principal investigator, Erasme University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01801332
- Sponsor's protocol ID
- NETI HAA
- Status last verified
- Feb 2013
- First submitted
- 27 Feb 2013
- Last updated
- 28 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 26764182
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intensive Enteral Nutrition in Association With Corticosteroids in Severe Acute Alcoholic Hepatitis: a Multicenter, Randomized, Controlled Trial
- ClinicalTrials.gov ID
- NCT01801332
- Acronym / sponsor ID
- NETI HAA
- Conditions
- Severe Alcoholic Hepatitis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 136 participants (actual)
- Lead sponsor
- Erasme University HospitalUniversity, hospital or other
- Study start
- Feb 2010
- Primary completion
- Feb 2013 (actual)
- First posted
- 28 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| intensive arm | Experimental | Dietary Supplement: intensive nutritionCorticosteroïds (Methylprednisolone 32 mg/d) for 28 days + intensive enteral nutrition by feeding tube for 14 days |
| control arm | Active comparator | Dietary Supplement: usual mealsCorticosteroïds (Methylprednisolone 32 mg/d) for 28 days + " classical " oral alimentation for 14 days |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| intensive nutritionPatients 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. | Dietary supplement | intensive arm |
| usual mealsPatients 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. | Dietary supplement | control arm |
Primary outcome
survival
Time frame: 6 months survival
1 secondary outcome
survival
Time frame: 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2013.
- Derived from this study: PubMed 26764182Moreno 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christophe Moreno, MD, PhD principal investigator
Erasme University Hospital
19 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing intensive nutrition and usual meals in people with Severe Alcoholic Hepatitis, run by Erasme University Hospital at 19 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Belgium, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
survival (time frame: 6 months survival). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01801332, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2013.