National Cohort of Uncomplicated Alcoholic Cirrhosis (CIRRAL)
|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|
- HCC Occurrence [ Time Frame: 3 years ] [ Designated as safety issue: No ]cumulative incidence within 3 years
- 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
- Alcohol- and cirrhosis-related event free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]event free survival where events are ascitis, digestive hemorrhage, icterus, encephalopathy, non-liver events related to alcohol, bacterial infection and death free of those events
Biospecimen Retention: Samples With DNA
|Study Start Date:||October 2010|
|Estimated Study Completion Date:||October 2017|
|Estimated Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
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.
- description of the incidence of HCC occurrence in patients with alcoholic cirrhosis;
- 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.).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01213927
|Jean Verdier hospital (AP-HP)|
|Bondy, France, 93140|
|Principal Investigator:||Nathalie GANNE, MD PhD||Assistance Publique - Hôpitaux de Paris|