Liver Transplantation in Alcoholic Hepatitis (SETH-HA)

This study has suspended participant recruitment.
(Low rate of recruitment (only one patient up to May 2014))
Sponsor:
Collaborator:
Fundación Mutua Madrileña
Information provided by (Responsible Party):
Sociedad Española de Trasplante Hepático
ClinicalTrials.gov Identifier:
NCT01768715
First received: December 29, 2012
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

Patients with alcoholic hepatitis non-responsive to steroids have a poor prognosis. Recently a French-Belgian prospective study has obtained good results (acceptable survival with a low rate of alcohol recidivism).

The hypothesis of the present study is that carefully selected Spanish patients with alcoholic hepatitis that do not respond to steroid therapy may have a good survival if they receive a liver transplant. The expected rate of alcohol recidivism in such a selected population will be low.


Condition
Alcoholic Hepatitis

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Applicability of Liver Transplantation in Alcoholic Hepatitis

Resource links provided by NLM:


Further study details as provided by Sociedad Española de Trasplante Hepático:

Primary Outcome Measures:
  • Evaluate survival of patients with severe alcoholic hepatitis non responsive to therapy after liver transplantation [ Time Frame: 1 year after the diagnosis of alcoholic hepatitis ] [ Designated as safety issue: No ]
    The survival of patients transplanted with alcoholic hepatitis is going to be compared with the survival of patients with alcoholic hepatitis that are not considered adequate for liver transplantation


Secondary Outcome Measures:
  • Evaluate the applicability of liver transplantation in patients with alcoholic hepatitis non responsive to steroid therapy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The applicability of liver transplantation is defined as the ratio between the number of patients transplanted for alcoholic hepatitis and the number of patients with severe alcoholic hepatitis that do not respond to steroid therapy.

  • Evaluate the mortality in waiting list for transplantation of patients with alcoholic hepatitis unresponsive to steroid therapy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Proportion of patients who are accepted as candidates for liver transplantation who die before transplantation.

  • Evaluate the rate of alcohol recidivism after liver transplantation for alcoholic hepatitis [ Time Frame: 1, 2, 3, 4 and 5 years ] [ Designated as safety issue: Yes ]
    Proportion of patients transplanted for alcoholic hepatitis that have a recurrence in alcohol consumption

  • Evaluate survival of patients with alcoholic hepatitis after liver transplantation. [ Time Frame: 2, 3, 4 and 5 years after the diagnosis of alcoholic hepatitis ] [ Designated as safety issue: No ]
    The survival of patients transplanted with alcoholic hepatitis is going to be compared with the survival of patients with alcoholic hepatitis that are not considered adequate for liver transplantation


Estimated Enrollment: 40
Study Start Date: January 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Good response
Patients with severe alcoholic hepatitis and good response to therapy.
Non transplant candidates
Patients with severe alcoholic hepatitis and poor response to therapy, that are not candidates to transplantation, according to the specified criteria.
Transplant candidates
Patients with severe alcoholic hepatitis and poor response to therapy, that are candidates to transplantation, according to the specified criteria.

Detailed Description:

This is a open prospective multicenter study. Nineteen liver transplant units in Spain will take part in it.

Inclusion criteria for patients:

  1. Diagnosis of alcoholic hepatitis (liver biopsy will be advisable).
  2. First episode of clinical decompensation of alcoholic liver disease (defined as jaundice, variceal bleeding, ascites or portal-systemic encephalopathy).
  3. Absence of a high risk of alcoholic recidivism (according to De Gottardi, et al).
  4. Severe alcoholic hepatitis (ABIC score > 6.71)
  5. Informed consent

Exclusion criteria :

  1. Age over 65 years.
  2. Hepatitis B or C or HIV infections.
  3. Uncontrolled bacterial infection
  4. Other liver diseases, such as alpha-1-antitrypsin deficiency, primary biliary cirrhosis, ...
  5. Morbid obesity (BMI > 35 kg/m2)
  6. Major uncontrolled psychiatric disease
  7. Drug addiction (excluding tobacco) in the last two years.
  8. Absence of informed consent.
  9. Acute-on-chronic liver disease.
  10. Paracetamol consumption over 10 grams in the last week.

Criteria for liver transplantation.

  1. Absence of response to steroid therapy (Lille score ≥ 0.45 7 days after initiation of steroid therapy).
  2. Adequate social and familiar environment.
  3. Complete agreement in the medical staff about the candidate to transplantation.
  4. Absence of bacterial or fungal infection.

Three groups of patients will be formed:

Group 1. Patients with severe alcoholic hepatitis and good response to therapy. Group 2. Patients with severe alcoholic hepatitis and poor response to therapy, that are not candidates to transplantation.

Group 3. Patients with severe alcoholic hepatitis and poor response to therapy, that are candidates to transplantation.

A complete follow-up of the patients would be extended to five years. The survival of these three groups will be compared. Survival of liver transplant recipients should also be compared with survival of other liver transplant recipients.

Alcohol recidivism should also be studied in all the patients of the study. Sample size estimation: According to the data published by Mathurin et al, 28 patients treated with liver transplantation and 28 non-transplanted patients with severe alcoholic hepatitis should be necessary.

Interim analysis after every 10 transplanted patients should be performed. The study will be interrupted if the differences in the survivals between groups 2 and 3 reaches a significance of 0.01. In case this significance is not reached the inclusion of patients should end when 40 patients are transplanted. This sample size is estimated to be reached in 18-24 months.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with alcoholic hepatitis participating in this trial are going to be selected from patients admitted to the hospital (from the emergency department or referred from other hospital)

Criteria

Inclusion Criteria:

  1. Diagnosis of alcoholic hepatitis (liver biopsy will be advisable).
  2. First episode of clinical decompensation of alcoholic liver disease (defined as jaundice, variceal bleeding, ascites or portal-systemic encephalopathy).
  3. Absence of a high risk of alcoholic recidivism (according to De Gottardi, et al).
  4. Severe alcoholic hepatitis (ABIC score > 6.71)
  5. Informed consent

Exclusion Criteria:

  1. Age over 65 years.
  2. Hepatitis B or C or HIV infections.
  3. Uncontrolled bacterial infection
  4. Other liver diseases, such as alpha-1-antitrypsin deficiency, primary biliary cirrhosis, ...
  5. Morbid obesity (BMI > 35 kg/m2)
  6. Major uncontrolled psychiatric disease
  7. Drug addiction (excluding tobacco) in the last two years.
  8. Absence of informed consent.
  9. Acute-on-chronic liver disease.
  10. Paracetamol consumption over 10 grams in the last week.

Criteria for liver transplantation.

  1. Absence of response to steroid therapy (Lille score ≥ 0.45 7 days after initiation of steroid therapy).
  2. Adequate social and familiar environment.
  3. Complete agreement in the medical staff about the candidate to transplantation.
  4. Absence of bacterial or fungal infection.
  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: NCT01768715

Locations
Spain
Hospital Central de Asturias
Oviedo, Asturias, Spain
Hospital Marqués de Valdecilla
Santander, Cantabria, Spain
Hospital Clínico Universitario de Santiago
Santiago de Compostela, La Coruña, Spain
Hospital Puerta de Hierro
Majadahonda, Madrid, Spain
Clínica Universidad de Navarra
Pamplona, Navarra, Spain
Hospital Vall d'Hebrón
Barcelona, Spain
Hospital Reina Sofía
Córdoba, Spain
Hospital Virgen de la Nieves
Granada, Spain
Complejo Hospitalario Universitario de la Coruña
La Coruña, Spain
Hospital Ramón y Cajal
Madrid, Spain
Hospital Gregorio Marañón
Madrid, Spain
Hospital Virgen de la Arrixaca
Murcia, Spain
Hospital Carlos Haya
Málaga, Spain
Hospital Virgen del Rocío
Sevilla, Spain
Hospital La Fe
Valencia, Spain
Hospital Río Hortega
Valladolid, Spain
Hospital Lozano Blesa
Zaragoza, Spain
Sponsors and Collaborators
Sociedad Española de Trasplante Hepático
Fundación Mutua Madrileña
Investigators
Study Chair: Ignacio Herrero, MD Clinica Universidad de Navarra
Study Chair: Santiago Tome, MD Complejo Hospitalario Universitario de Santiago
Study Chair: Ignacio Gonzalez-Pinto, MD Hospital Central de Asturias
  More Information

Publications:
Responsible Party: Sociedad Española de Trasplante Hepático
ClinicalTrials.gov Identifier: NCT01768715     History of Changes
Other Study ID Numbers: SETH-HA
Study First Received: December 29, 2012
Last Updated: June 2, 2014
Health Authority: Spain: Comité Ético de Investigación Clínica

Keywords provided by Sociedad Española de Trasplante Hepático:
Alcoholic hepatitis
Liver transplantation
Survival
Alcoholism

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

ClinicalTrials.gov processed this record on September 18, 2014