National Cohort of Uncomplicated Alcoholic Cirrhosis (CIRRAL)

This study is currently recruiting participants.
Verified April 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborators:
National Cancer Institute, France
French National Agency for Research on AIDS and Viral Hepatitis
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01213927
First received: October 1, 2010
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

Hepatocellular carcinoma (HCC) is a major public health problem, whose incidence is increasing in developed countries and is the leading cause of death in patients with cirrhosis. The diagnosis and the early management are key issues that could improve the prognosis. In France, alcoholic cirrhosis is the leading cause of HCC, while the aetiology of underlying chronic liver disease is mainly hepatitis C (HCV) in Southern Europe and Japan, and hepatitis B (HBV) in Asia and Africa. In the next years, due to the improved results of anti-viral therapies, this trend should be reinforced with a decreasing proportion of HCC related to viral cirrhosis and an increasing proportion of HCC related to alcoholic cirrhosis. However, natural history of alcoholic cirrhosis remains poorly understood, most studies being retrospective and including a small number of patients. This project is filed by the consortium CIRRAL including French Academic hospitals centers currently involved and referees in the field of alcoholic liver disease and HCC (8 at the moment, and more in the next months). It is a national multicenter prospective study that will include 1200 patients with alcoholic cirrhosis histologically proven over 3 years. The main goal of this cohort is to describe the natural history of a large number of patients with alcoholic cirrhosis prospectively followed, and to identify predictors of the occurrence of HCC.


Condition
Alcoholic Cirrhosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: CIRRAL: Hepatocellular Carcinoma in Patients With Uncomplicated Alcoholic Cirrhosis: Incidence and Predictive Factors. A Multicentric Prospective Cohort

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • HCC Occurrence [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    cumulative incidence within 3 years


Secondary Outcome Measures:
  • Mortality [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    overall mortality - whatever the cause of death

  • Liver-related mortality [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    cumulative incidence of liver-related deaths


Biospecimen Retention:   Samples With DNA

At enrollement, 20 ml of blood will be collected for freezing and storage of serum and plasma, and constitution of a DNA library


Estimated Enrollment: 1200
Study Start Date: October 2010
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Detailed Description:

Patients will be selected for the study if they met all the inclusion criteria, without any of the non-inclusion criteria, ie compensated Child Pugh A alcoholic cirrhosis without viral chronic hepatitis B or C, and without any detectable HCC. They will be offered, during a consultation as part of their usual care, to participate in the study. An information note will be issued. Patients agreeing to participate should date and sign informed consent. Usual biological tests and liver ultrasonography will be performed if not done within 90 days prior to inclusion. During this visit, 20 ml of blood will be collected for freezing and storage of serum and plasma, and constitution of a DNA library.

From the reviews conducted at baseline, patients with at least one exclusion criteria (ie decompensation of cirrhosis, Child Pugh score ≥ 7, co-infection with HBV or HCV, or liver focal lesion suggestive of HCC will be excluded (and their serum samples achieved for the BioBank will be destroyed):

Monitoring: According to current guidelines, patients will have periodical surveillance with liver ultrasonography and medical consultation at least every 6 months, blood tests at least every year, periodic assessment of esophageal and gastric varices (every 1 to 3 years) and prevention of their rupture if any. An additional blood sampling of 20 ml will be taken at baseline and every year in order to perform serum, plasma, and DNA libraries; Data will be standardized and centralized in a single database.

Statistical Analysis: Methods for censored data with competitive risks. Number of subjects to include: The planned number is 1200 subjects included in 3 years. Assuming a minimal annual incidence of HCC about 2% in patients with alcoholic cirrhosis, and a proportion of lost to follow-up of around 20% in this poorly compliant population, a sample of 3000 patients could demonstrate the existence of predictive factors for the occurrence of HCC associated with a relative risk at least equal to 2, with a power of 90%. However, the enrollment of 3000 patients recruited in three years is not a realistic goal. For practical reasons and since the data currently available are very limited regarding the precise incidence of HCC and the strength of association between risk factors and HCC in patients with alcoholic cirrhosis, the minimum number of patients included in the cohort CIRRAL was set at 1200. Regarding an expected percentage of patients lost to follow close to 20%, the final number of patients with sufficient follow-up will be 1000.

Expected results

  1. description of the incidence of HCC occurrence in patients with alcoholic cirrhosis;
  2. identification of predictive factors for the occurrence of HCC c) identification of prognostic factors for survival. In addition, nested scientific projects will use the database and collected samples of this prospective cohort, thus constituting significant savings of resources. However, these nested scientific projects should include a specific need of organization and financing clean, and may involve only a fraction of the population included. The areas involved are very varied (immunology, genetics, imaging, evaluation of fibrosis, biostatistics, , quality of life, economy, etc.).
  Eligibility

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

French primary care hospitals

Criteria

Inclusion Criteria:

  • age ≥ 18 years
  • histologically proven cirrhosis
  • no previous HCC (treated or not )
  • excessive consumption of alcohol, considered as the main cause of cirrhosis
  • signed informed consent.

Exclusion Criteria:

  • serious associated short-term life threatening disease (except associated HIV viral infection and the liver disease itself),
  • decompensation of cirrhosis (bleeding or ascites),
  • co-infection with HBV or HCV;
  • liver focal lesion suggestive of HCC
  • Child Pugh score ≥ 7 (Class B or C).
  • patient under guardianship
  • pregnant women
  • inability to regular monitoring, for whatever reason
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01213927

Contacts
Contact: Nathalie GANNE, MD PH +33(0)1 48 02 62 94 nathalie.ganne@jvr.aphp.fr

Locations
France
Jean Verdier hospital (AP-HP) Recruiting
Bondy, France, 93140
Contact: Nathalie GANNE, MD PhD    33148026294    nathalie.ganne@jvr.aphp.fr   
Contact: Valérie BOURCIER, MD    33148026280    valerie.bourcier@jvr.aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
National Cancer Institute, France
French National Agency for Research on AIDS and Viral Hepatitis
Investigators
Principal Investigator: Nathalie GANNE, MD PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01213927     History of Changes
Other Study ID Numbers: NI09020
Study First Received: October 1, 2010
Last Updated: April 22, 2014
Health Authority: France: Ministry of Health

Additional relevant MeSH terms:
Liver Cirrhosis
Fibrosis
Liver Cirrhosis, Alcoholic
Carcinoma, Hepatocellular
Liver Diseases
Digestive System Diseases
Pathologic Processes
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on April 22, 2014