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
NCT ID: NCT06263816
Last Updated: 2025-06-04
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
NOT_YET_RECRUITING
PHASE3
290 participants
INTERVENTIONAL
2025-06-17
2030-07-17
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Study on B-blockers to Prevent Decompensation of Cirrhosis With HTPortal
NCT01059396
Acute hemodynamiC Response To Carvedilol Predicts Survival in ACLF Patients
NCT06298656
Acute Hemodynamic Response to Carvedilol in Children With Clinically Significant Portal Hypertension.
NCT05767229
Efficacy of Nonselective Beta Blocker vs Placebo in Patients With Acute-on-chronic Liver Failure With Small/ no Esophageal Varices
NCT02583698
Efficacy and Safety of Carvedilol in Cirrhosis Patients With Uncomplicated Ascites Without High Risk Esophageal Varices
NCT05057572
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Portal hypertension (PH) is the strongest predictor of decompensation. Hepatic venous pressure gradient (HVPG) is the reference standard for the evaluation of PH. HVPG ≥10 mm Hg, called "clinically significant portal hypertension", identifies a population with a high risk of decompensation. HVPG measurement is an invasive procedure, only routinely available in expert centers. Liver stiffness measurement (LSM) using transient elastography (TE) (referred as TE LSM) using Fibroscan can provide an indirect estimate of HVPG. TE-LSM ≥ 25 kPa can rule-in HVPG ≥10 mm Hg with a specificity \>90%.
Nonselective beta-blockers (NSBBs) lower portal pressure by decreasing portal venous inflow. Carvedilol also decreases intrahepatic vascular resistance, and thereby achieves a greater reduction in portal pressure than propranolol. At low-dose (≤12.5 mg/day), carvedilol is safe in patients with compensated cirrhosis.
In patients with asymptomatic cirrhosis, NSBBs were recommended when medium or large varices (high-risk varices) are present for prophylaxis of variceal bleeding. In a recent randomized controlled trial, the PREDESCI study (NCT01059396), NSBBs reduced incidence of decompensation or death in patients with compensated cirrhosis with clinically significant portal hypertension. In the PREDESCI study, the diagnosis of clinically significant portal hypertension was based on invasive HVPG measurement, so that its results are not applicable in clinical practice.
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 randomized controlled trial.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Carvédilol
Experimental group: Patients will be treated with carvedilol.
Patients will receive the number of pills of carvedilol corresponding to the dose determined during the titration period (either one pill of 6.25 mg in the morning or 1 pill of 6.25 mg twice a day, 1 in the morning and 1 in the evening.
Placebo
Control group: Patients will receive a placebo.
Patients will receive the number of pills of placebo corresponding to the dose determined during the titration period (either one pill in the morning or 1 pill twice a day: 1 in the morning and 1 in the evening).
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Experimental group: Patients will be treated with carvedilol.
Patients will receive the number of pills of carvedilol corresponding to the dose determined during the titration period (either one pill of 6.25 mg in the morning or 1 pill of 6.25 mg twice a day, 1 in the morning and 1 in the evening.
Control group: Patients will receive a placebo.
Patients will receive the number of pills of placebo corresponding to the dose determined during the titration period (either one pill in the morning or 1 pill twice a day: 1 in the morning and 1 in the evening).
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Centre Hospitalier Universitaire Amiens Picardie
UNKNOWN
Centre Hospitalier Universitaire Angers
UNKNOWN
Assistance Publique Hopitaux Paris BEAUJON
UNKNOWN
Centre Hospitalier Universitaire Caen
UNKNOWN
Centre Hospitalier intercommunal de Créteil
UNKNOWN
Hospices Civils de Lyon
OTHER
Centre Hospitalier Universitaire Grenoble
UNKNOWN
Centre Hospitalier Universitaire Haut Lévêque
UNKNOWN
Centre Hospitalier Régional Universitaire Lille
UNKNOWN
Centre Hospitalier Universitaire Jean Minjoz
UNKNOWN
Assistance Publique Hopitaux Paris AVICENNE
UNKNOWN
Centre Hospitalier Universitaire Clermont Ferrand
UNKNOWN
Assistance Publique Hopitaux Paris LA PITIE SALPETRIERE
UNKNOWN
Centre Hospitalier Universitaire Pontchaillou
UNKNOWN
Assistance Publique Hopitaux Paris ST ANTOINE
UNKNOWN
Assistance Publique Hopitaux Paris PAUL BROUSSE
UNKNOWN
University Hospital, Montpellier
OTHER
Assistance Publique Hopitaux Paris HENRI MONDOR
UNKNOWN
Centre Hospitaliser Départemental de Vendée
UNKNOWN
Nantes University Hospital
OTHER
Centre Hospitalier Universitaire Dijon
OTHER
CHU de Reims
OTHER
Hôpitaux Universitaires de Strasbourg
UNKNOWN
University Hospital, Toulouse
OTHER
University Hospital, Tours
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Laure ELKRIEF, MD-PhD
Role: STUDY_DIRECTOR
University Hospital, Tours
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
CHU Amiens Picardie
Amiens, , France
CHU Angers
Angers, , France
CHU Beaujon
Assistance Publique Hôpitaux de Paris, , France
CHU Jean Minjoz
Besançon, , France
CHU Haut Lévêque
Bordeaux, , France
CHU Caen
Caen, , France
CH intercommunal de Créteil
CH Intercommunal de Créteil, , France
CHU Clermont Ferrand
Clermont-Ferrand, , France
Hôpital Henri Mondor
Créteil, , France
Hôpital Francois Mitterrand
Dijon, , France
CHU Grenoble
Grenoble, , France
Centre Hospitalier départemental de Vendée
La Roche-sur-Yon, , France
Hôpital Huriez
Lille, , France
CHU la Croix Rousse
Lyon, , France
CHU de Montpellier
Montpellier, , France
CHU Hôtel Dieu
Nantes, , France
CHU Avicenne
Paris, , France
CHU Pitié-Salpêtrière
Paris, , France
CHU Saint-Antoin
Paris, , France
CHU de Reims
Reims, , France
CHU Pontchaillou
Rennes, , France
Hôpitaux Universitaires de Strasbourg
Strasbourg, , France
CHU de Toulouse
Toulouse, , France
Hôpital Paul Brousse
Villejuif, , France
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CARVECIR
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.