NCT06263816

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
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 290 (estimated)
• Sponsor: University Hospital, Tours · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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. 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

• Asymptomatic Cirrhosis
• Clinically Significant Portal Hypertension

Interventions

Type	Name	Description
DRUG	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.
OTHER	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).

Timeline

• Start date: 2025-06-17
• Primary completion: 2027-07-17
• Completion: 2030-07-17
• First posted: 2024-02-16
• Last updated: 2025-06-04

Locations

24 sites across 1 country: France