Alcoholic HepatitisSETH-HANCT01768715
Liver Transplantation in Alcoholic Hepatitis
An observational study of Alcoholic Hepatitis, run by Sociedad Española de Trasplante Hepático at 17 sites in Spain.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alcoholic Hepatitis
- How many people
- 40 participants
- Where
- 17 sitesSpain
- Study dates
- Jan 2013to Dec 2017
- Phase
- Observational
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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)
Who may be able to join
- Diagnosis of alcoholic hepatitis (liver biopsy will be advisable).
- First episode of clinical decompensation of alcoholic liver disease (defined as jaundice, variceal bleeding, ascites or portal-systemic encephalopathy).
- Absence of a high risk of alcoholic recidivism (according to De Gottardi, et al).
- Severe alcoholic hepatitis (ABIC score > 6.71)
- Informed consent
Who cannot join
- Age over 65 years.
- Hepatitis B or C or HIV infections.
- Uncontrolled bacterial infection
- Other liver diseases, such as alpha-1-antitrypsin deficiency, primary biliary cirrhosis, ...
- Morbid obesity (BMI > 35 kg/m2)
- Major uncontrolled psychiatric disease
Show all 15Show fewer
- Drug addiction (excluding tobacco) in the last two years.
- Absence of informed consent.
- Acute-on-chronic liver disease.
- Paracetamol consumption over 10 grams in the last week.
- Criteria for liver transplantation.
- Absence of response to steroid therapy (Lille score ≥ 0.45 7 days after initiation of steroid therapy).
- Adequate social and familiar environment.
- Complete agreement in the medical staff about the candidate to transplantation.
- Absence of bacterial or fungal infection.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
Spain17 sites
Complejo Hospitalario Universitario de la Coruña
A Coruña, La Coruña
Hospital Vall d'Hebrón
Barcelona, Barcelona
Hospital Reina Sofía
Córdoba, Córdoba
Hospital Virgen de la Nieves
Granada, Granada
Hospital Gregorio Marañón
Madrid, Madrid
Hospital Ramón y Cajal
Madrid, Madrid
Hospital Puerta de Hierro
Majadahonda, Madrid
Hospital Carlos Haya
Málaga, Málaga
Hospital Virgen de la Arrixaca
Murcia, Murcia
Hospital Central de Asturias
Oviedo, Principality of Asturias
Clínica Universidad de Navarra
Pamplona, Navarre
Hospital Marqués de Valdecilla
Santander, Cantabria
Hospital Clínico Universitario de Santiago
Santiago de Compostela, La Coruña
Hospital Virgen del Rocío
Seville, Sevilla
Hospital La Fe
Valencia, Valencia
Hospital Río Hortega
Valladolid, Valladolid
Hospital Lozano Blesa
Zaragoza, Zaragoza
About this study
Official title: Applicability of Liver Transplantation in Alcoholic Hepatitis
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.
Read the detailed description
This is a open prospective multicenter study. Nineteen liver transplant units in Spain will take part in it.
Inclusion criteria for patients:
- Diagnosis of alcoholic hepatitis (liver biopsy will be advisable).
- First episode of clinical decompensation of alcoholic liver disease (defined as jaundice, variceal bleeding, ascites or portal-systemic encephalopathy).
- Absence of a high risk of alcoholic recidivism (according to De Gottardi, et al).
- Severe alcoholic hepatitis (ABIC score > 6.71)
- Informed consent
Exclusion criteria :
- Age over 65 years.
- Hepatitis B or C or HIV infections.
- Uncontrolled bacterial infection
- Other liver diseases, such as alpha-1-antitrypsin deficiency, primary biliary cirrhosis, ...
- Morbid obesity (BMI > 35 kg/m2)
- Major uncontrolled psychiatric disease
- Drug addiction (excluding tobacco) in the last two years.
- Absence of informed consent.
- Acute-on-chronic liver disease.
- Paracetamol consumption over 10 grams in the last week.
Criteria for liver transplantation.
- Absence of response to steroid therapy (Lille score ≥ 0.45 7 days after initiation of steroid therapy).
- Adequate social and familiar environment.
- Complete agreement in the medical staff about the candidate to transplantation.
- 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.
- Conditions
- Alcoholic Hepatitis
- Keywords
- Alcoholic hepatitis, Liver transplantation, Survival, Alcoholism
- Medical subject headings
- Hepatitis, Alcoholic, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate survival of patients with severe alcoholic hepatitis non responsive to therapy after liver transplantation
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
Measured: 1 year after the diagnosis of alcoholic hepatitis
Secondary outcomes (4)
Evaluate the applicability of liver transplantation in patients with alcoholic hepatitis non responsive to steroid therapy
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.
Measured: 1 year
Evaluate the mortality in waiting list for transplantation of patients with alcoholic hepatitis unresponsive to steroid therapy
Proportion of patients who are accepted as candidates for liver transplantation who die before transplantation.
Measured: 1 year
Evaluate the rate of alcohol recidivism after liver transplantation for alcoholic hepatitis
Proportion of patients transplanted for alcoholic hepatitis that have a recurrence in alcohol consumption
Measured: 1, 2, 3, 4 and 5 years
Evaluate survival of patients with alcoholic hepatitis after liver transplantation.
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
Measured: 2, 3, 4 and 5 years after the diagnosis of alcoholic hepatitis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2013 (estimated)
- Study startJan 2013
- Primary completionDec 2014 (estimated)
- Study completionDec 2017 (estimated)
Why it stopped: Low rate of recruitment (only one patient up to May 2014)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sociedad Española de Trasplante Hepático
- Sponsor type
- Research network
- Collaborators
- Fundación Mutua Madrileña
- Responsible party
- Sponsor
- Investigators
- Ignacio Herrero, MD, Study chair, Clinica Universidad de NavarraSantiago Tome, MD, Study chair, Complejo Hospitalario Universitario de SantiagoIgnacio Gonzalez-Pinto, MD, Study chair, Hospital Central de Asturias
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01768715
- Sponsor's protocol ID
- SETH-HA
- Acronym
- SETH-HA
- Status last verified
- Jun 2014
- First submitted
- 29 Dec 2012
- Last updated
- 3 Jun 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Dominguez M, Rincon D, Abraldes JG, Miquel R, Colmenero J, Bellot P, Garcia-Pagan JC, Fernandez R, Moreno M, Banares R, Arroyo V, Caballeria J, Gines P, Bataller R. A new scoring system for prognostic stratification of patients with alcoholic hepatitis. Am J Gastroenterol. 2008 Nov;103(11):2747-56. doi: 10.1111/j.1572-0241.2008.02104.x. Epub 2008 Aug 21.
PubMed 18721242Tome S, Martinez-Rey C, Gonzalez-Quintela A, Gude F, Brage A, Otero E, Abdulkader I, Forteza J, Bustamante M, Varo E. Influence of superimposed alcoholic hepatitis on the outcome of liver transplantation for end-stage alcoholic liver disease. J Hepatol. 2002 Jun;36(6):793-8. doi: 10.1016/s0168-8278(02)00047-8.
PubMed 12044530Wells JT, Said A, Agni R, Tome S, Hughes S, Dureja P, Lucey MR. The impact of acute alcoholic hepatitis in the explanted recipient liver on outcome after liver transplantation. Liver Transpl. 2007 Dec;13(12):1728-35. doi: 10.1002/lt.21298.
PubMed 18044757Mathurin P, Moreno C, Samuel D, Dumortier J, Salleron J, Durand F, Castel H, Duhamel A, Pageaux GP, Leroy V, Dharancy S, Louvet A, Boleslawski E, Lucidi V, Gustot T, Francoz C, Letoublon C, Castaing D, Belghiti J, Donckier V, Pruvot FR, Duclos-Vallee JC. Early liver transplantation for severe alcoholic hepatitis. N Engl J Med. 2011 Nov 10;365(19):1790-800. doi: 10.1056/NEJMoa1105703.
PubMed 22070476
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Applicability of Liver Transplantation in Alcoholic Hepatitis
- ClinicalTrials.gov ID
- NCT01768715
- Acronym / sponsor ID
- SETH-HA / SETH-HA
- Conditions
- Alcoholic Hepatitis
- Keywords
- Alcoholic hepatitis, Liver transplantation, Survival, Alcoholism
- Study type
- Observational
- Recruitment status
- SuspendedReason stopped: Low rate of recruitment (only one patient up to May 2014)
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Sociedad Española de Trasplante HepáticoResearch network
- Collaborators
- Fundación Mutua Madrileña
- Study start
- Jan 2013
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 15 Jan 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.
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.
Detailed description
This is a open prospective multicenter study. Nineteen liver transplant units in Spain will take part in it.
Inclusion criteria for patients:
- Diagnosis of alcoholic hepatitis (liver biopsy will be advisable).
- First episode of clinical decompensation of alcoholic liver disease (defined as jaundice, variceal bleeding, ascites or portal-systemic encephalopathy).
- Absence of a high risk of alcoholic recidivism (according to De Gottardi, et al).
- Severe alcoholic hepatitis (ABIC score > 6.71)
- Informed consent
Exclusion criteria :
- Age over 65 years.
- Hepatitis B or C or HIV infections.
- Uncontrolled bacterial infection
- Other liver diseases, such as alpha-1-antitrypsin deficiency, primary biliary cirrhosis, ...
- Morbid obesity (BMI > 35 kg/m2)
- Major uncontrolled psychiatric disease
- Drug addiction (excluding tobacco) in the last two years.
- Absence of informed consent.
- Acute-on-chronic liver disease.
- Paracetamol consumption over 10 grams in the last week.
Criteria for liver transplantation.
- Absence of response to steroid therapy (Lille score ≥ 0.45 7 days after initiation of steroid therapy).
- Adequate social and familiar environment.
- Complete agreement in the medical staff about the candidate to transplantation.
- 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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)
Key inclusion criteria (5 listed)
- Diagnosis of alcoholic hepatitis (liver biopsy will be advisable).
- First episode of clinical decompensation of alcoholic liver disease (defined as jaundice, variceal bleeding, ascites or portal-systemic encephalopathy).
- Absence of a high risk of alcoholic recidivism (according to De Gottardi, et al).
- Severe alcoholic hepatitis (ABIC score > 6.71)
- Informed consent
Key exclusion criteria (15 listed)
- Age over 65 years.
- Hepatitis B or C or HIV infections.
- Uncontrolled bacterial infection
- Other liver diseases, such as alpha-1-antitrypsin deficiency, primary biliary cirrhosis, ...
- Morbid obesity (BMI > 35 kg/m2)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
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
4 secondary outcomes
Evaluate the applicability of liver transplantation in patients with alcoholic hepatitis non responsive to steroid therapy
Time frame: 1 year
Evaluate the mortality in waiting list for transplantation of patients with alcoholic hepatitis unresponsive to steroid therapy
Time frame: 1 year
Evaluate the rate of alcohol recidivism after liver transplantation for alcoholic hepatitis
Time frame: 1, 2, 3, 4 and 5 years
Evaluate survival of patients with alcoholic hepatitis after liver transplantation.
Time frame: 2, 3, 4 and 5 years after the diagnosis of alcoholic hepatitis
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2014.
- Background: PubMed 18721242Dominguez M, Rincon D, Abraldes JG, Miquel R, Colmenero J, Bellot P, Garcia-Pagan JC, Fernandez R, Moreno M, Banares R, Arroyo V, Caballeria J, Gines P, Bataller R. A new scoring system for prognostic stratification of patients with alcoholic hepatitis. Am J Gastroenterol. 2008 Nov;103(11):2747-56. doi: 10.1111/j.1572-0241.2008.02104.x. Epub 2008 Aug 21.
- Background: PubMed 12044530Tome S, Martinez-Rey C, Gonzalez-Quintela A, Gude F, Brage A, Otero E, Abdulkader I, Forteza J, Bustamante M, Varo E. Influence of superimposed alcoholic hepatitis on the outcome of liver transplantation for end-stage alcoholic liver disease. J Hepatol. 2002 Jun;36(6):793-8. doi: 10.1016/s0168-8278(02)00047-8.
- Background: PubMed 18044757Wells JT, Said A, Agni R, Tome S, Hughes S, Dureja P, Lucey MR. The impact of acute alcoholic hepatitis in the explanted recipient liver on outcome after liver transplantation. Liver Transpl. 2007 Dec;13(12):1728-35. doi: 10.1002/lt.21298.
- Background: PubMed 22070476Mathurin P, Moreno C, Samuel D, Dumortier J, Salleron J, Durand F, Castel H, Duhamel A, Pageaux GP, Leroy V, Dharancy S, Louvet A, Boleslawski E, Lucidi V, Gustot T, Francoz C, Letoublon C, Castaing D, Belghiti J, Donckier V, Pruvot FR, Duclos-Vallee JC. Early liver transplantation for severe alcoholic hepatitis. N Engl J Med. 2011 Nov 10;365(19):1790-800. doi: 10.1056/NEJMoa1105703.
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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.
Ignacio Herrero, MD study chair
Clinica Universidad de Navarra
Santiago Tome, MD study chair
Complejo Hospitalario Universitario de Santiago
Ignacio Gonzalez-Pinto, MD study chair
Hospital Central de Asturias
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alcoholic Hepatitis, run by Sociedad Española de Trasplante Hepático at 17 sites in Spain.
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 5 inclusion and 15 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: paused, as of the sponsor's last update on 3 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Spain. 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?
Results are not available in the source record.
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?
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). 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 NCT01768715, which also lists 4 linked publications.
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 3 Jun 2014.