NCT06263816

Brief Summary

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
290

participants targeted

Target at P50-P75 for phase_3

Timeline
51mo left

Started Jun 2025

Longer than P75 for phase_3

Geographic Reach
1 country

24 active sites

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress18%
Jun 2025Jul 2030

First Submitted

Initial submission to the registry

February 8, 2024

Completed
8 days until next milestone

First Posted

Study publicly available on registry

February 16, 2024

Completed
1.3 years until next milestone

Study Start

First participant enrolled

June 17, 2025

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 17, 2027

Expected
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 17, 2030

Last Updated

June 4, 2025

Status Verified

June 1, 2025

Enrollment Period

2.1 years

First QC Date

February 8, 2024

Last Update Submit

June 3, 2025

Conditions

Asymptomatic CirrhosisClinically Significant Portal Hypertension

Keywords

carvediloldecompensationdeathasymptomatic cirrhosissignificant portal hypertension

Outcome Measures

Primary Outcomes (1)

  • To evaluate the effect of low dose carvedilol (<=12.5 mg per day) versus placebo on the occurrence of decompensation of cirrhosis or liver-related death at 36 months

    Primary endpoint will be the occurrence, within 36 months after inclusion, of either decompensation of cirrhosis or liver-related death. Decompensation of cirrhosis is defined as a composite endpoint including one event among: overt ascites, overt hepatic encephalopathy and variceal bleeding according to Baveno VII consensus conference \[1\]. Liver-related death is defined as death occurring in the context of complicated ascites (e.g. spontaneous bacterial peritonitis or acute kidney injury), encephalopathy, variceal hemorrhage, or ACLF

    36 months

Study Arms (2)

Carvédilol

EXPERIMENTAL
Drug: Experimental group: Patients will be treated with carvedilol.

Placebo

PLACEBO COMPARATOR
Other: Control group: Patients will receive a placebo.

Interventions

Experimental group: Patients will be treated with carvedilol.DRUG

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.

Carvédilol
Control group: Patients will receive a placebo.OTHER

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).

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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

You may not qualify if:

  • 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
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

CHU Amiens Picardie

Amiens, France

Location

CHU Angers

Angers, France

Location

CHU Beaujon

Assistance Publique Hôpitaux de Paris, France

Location

CHU Jean Minjoz

Besançon, France

Location

CHU Haut Lévêque

Bordeaux, France

Location

CHU Caen

Caen, France

Location

CH intercommunal de Créteil

CH Intercommunal de Créteil, France

Location

CHU Clermont Ferrand

Clermont-Ferrand, France

Location

Hôpital Henri Mondor

Créteil, France

Location

Hôpital Francois Mitterrand

Dijon, France

Location

CHU Grenoble

Grenoble, France

Location

Centre Hospitalier départemental de Vendée

La Roche-sur-Yon, France

Location

Hôpital Huriez

Lille, France

Location

CHU la Croix Rousse

Lyon, France

Location

CHU de Montpellier

Montpellier, France

Location

CHU Hôtel Dieu

Nantes, France

Location

CHU Avicenne

Paris, France

Location

CHU Pitié-Salpêtrière

Paris, France

Location

CHU Saint-Antoin

Paris, France

Location

CHU de Reims

Reims, France

Location

CHU Pontchaillou

Rennes, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, France

Location

CHU de Toulouse

Toulouse, France

Location

Hôpital Paul Brousse

Villejuif, France

Location

MeSH Terms

Conditions

Death

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesCarbazolesIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsHeterocyclic Compounds, 3-Ring

Study Officials

  • Laure ELKRIEF, MD-PhD

    University Hospital, Tours

    STUDY DIRECTOR

Central Study Contacts

Laure ELKRIEF, MD-PhD

CONTACT

+33 247475965l.elkrief@chu-tours.fr

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: This study will be a national multicentric, phase III, superiority double-blinded randomized controlled trial with two parallel arms: carvedilol versus placebo. The primary end-point will be assessed by the local investigator (hepatologist), blinded of the randomization arm
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 8, 2024

First Posted

February 16, 2024

Study Start

June 17, 2025

Primary Completion (Estimated)

July 17, 2027

Study Completion (Estimated)

July 17, 2030

Last Updated

June 4, 2025

Record last verified: 2025-06

Data Sharing

IPD Sharing
Will not share

Locations

FR(24)