Effect of Long-term Carvedilol to Prevent Decompensation or Death in Patients With Asymptomatic Child-Pugh A5 to B8 Cirrhosis and Clinically Significant Portal Hypertension: a Multicenter Double-blind Randomized Control Trial
Status: Not yet recruiting

Decompensation of cirrhosis is a turning point in cirrhosis course, as associated with a marked decrease in life expectancy. Thus, prevention of decompensation is crucial.

The usefulness of carvedilol to prevent decompensation of cirrhosis in patients with TE-LSM ≥ 25 kPa as a surrogate marker for clinically significant portal hypertension, has never been evaluated in a clinical trial.

Eligibility:
- EligibilityCriteria: Inclusion Criteria:  Male or female≥ 18 years of age Cirrhosis related to hepatitis C or hepatitis B virus without viral replication for at least 2 years.  Or Cirrhosis related to alcohol consumption (active or abstinent) Or Cirrhosis related to metabolic syndrome or cryptogenic with BMI < 30 kg/m2  2 TE-LSM (Fibroscan®) performed in fasting conditions, using either the M or the XL probe >=25 kPa, within 12 months before inclusion Absence of medium or large varices or small varices with red signs at endoscopy within 3 months before inclusion Child-Pugh A5 to B8 Affiliation to a French social security system. Written informed consent obtained from the participant or participant's legal representative For child-bearing aged women, contraception using oral contraceptive, or intrauterine device or mechanical contraception  Exclusion Criteria:  History of overt ascites or encephalopathy <12 months before inclusion Treatment with either diuretics or lactulose or rifaximin <3 months before inclusion Any history of portal hypertension related bleeding Baseline heart rate <65/min or systolic blood pressure <100 mm Hg Previous transjugular intrahepatic portosystemic shunt (TIPSS) or liver transplantation Previous history or active hepatocellular carcinoma Glomerular filtration rate (CKD-Epi) < 30 mL/min Strict indication to selective or nonselective beta-blockers: history of acute myocardial infarction, congestive heart failure  Strict contraindication to selective or nonselective beta-blockers:  decompensated congestive heart failure grade 2 or 3 atrioventricular block sinus node dysfunction without pacemaker severe asthma according to WHO classification [63] severe Chronic Obstructive Pulmonary Disease, defined stage 3 or 4 of the GOLD classification, i.e.FEV1<50% of the predicted value (https://goldcopd.org/) severe Raynaud disease, defined as repetitive episodes of biphasic colour (at least two) of pallor, cyanosis, erythema, in addition to paresthesia or numbness, occurring in both cold and normal environments [64]. Known hypersensitivity to carvedilol Concomitant use of Cimétidin Concomitant use of class I antiarythmic agents (except lidocaïn) (i.e.cibenzoline, disopyramide, flécaïnide, hydroquinidine méxilétine, propafenone, quinidine) Concomitant use of calcium antagonists: diltiazem, vérapamil and bépridil Concomitant use of clonidine, méthyldopa, guanfacine, moxonidine, rilménidine Concomitant use of fingolimod Concomitant use of potent inhibitors (e.g. ketoconazole, HIV protease inhibitors) or inductors (e.g. rifampin, carbamazepine, phenytoin) of CYP3A4 (see appendix 7) Pregnancy or breastfeeding Non ability for participant to comply with the requirements of the study Life expectancy <12 months - HealthyVolunteers: No - Gender: All - MinimumAge: 18 Years - StdAgeList: Adult, Older Adult