Carvedilol vs. Propranolol in Second Prophylaxis of Variceal Bleeding

Sponsor

West China Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05651789

Collaborator

Chengdu Shangjin Nanfu Hospital (Other), West China Tianfu Hospital (Other)

160

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This randomized controlled trial was conducted to evaluate the efficacy and safety of carvedilol versus propranolol, combined with routine endoscopic treatment, in the secondary prophylaxis of variceal bleeding in patients with cirrhosis.

Condition or Disease	Intervention/Treatment	Phase
Portal Hypertension Varice Bleed Cirrhosis, Liver	Drug: Carvedilol Drug: Propranolol	N/A

Detailed Description

Non-selective beta blockers combined with endoscopic variceal band ligation (EVL) is the most effective methods for the prevention of variceal bleeding. Carvedilol has emerged as the preferred NSBB for treating portal hypertension in compensated cirrhosis due to strong evidence demonstrating that it has a more pronounced effect than propranolol to reduce the hepatic vein pressure gradient (HVPG), together with good patient acceptability and safety profile. However, No data from prospectively designed trials are available on the efficacy of carvedilol in the secondary prophylaxis of variceal bleeding. The aim of this randomized controlled trial was to evaluate the effectiveness and safety of carvedilol compared to propranolol as secondary prophylaxis of variceal bleeding in patients with cirrhosis. All cirrhotic patients with at least one episode of variceal bleeding were included and randomized to the carvedilol or propranolol groups. EVL protocol was routinely performed in both groups. Variceal rebleeding, further decompensation, liver-related death, and overall survival was the outcomes of this trial.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Randomized Controlled Trial on the Effectiveness and Safety of Carvedilol vs. Propranolol Combined With Endoscopic Treatment in Second Prophylaxis of Variceal Bleeding in Cirrhosis

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Carvedilol Carvedilol is started at a dose of 6.25mg/d, and titrated to a maximum dose of 12.5mg/d. Doses are increased 3 days later. Avoid systolic blood pressure <90 mmHg.	Drug: Carvedilol Carvedilol is started at a dose of 6.25mg/d, and titrated to a maximum dose of 12.5mg/d. Doses are increased 3 days later. Avoid systolic blood pressure <90 mmHg. Other Names: carvedilol as the nonselective beta-blockers
Active Comparator: Propranolol Propranolol is started at a dose of 20 mg/d and the dose will be increased by 10 mg twice a day steps every 2-3 days until the target (heart rate: 55~60 bpm) or to a maximum dose of 160 mg/d. Systolic arterial pressure is not less than 90 mm Hg and heart rate is not less than 50 bpm.	Drug: Propranolol Propranolol is started at a dose of 20 mg/d and the dose will be increased by 10 mg twice a day steps every 2-3 days until the target (heart rate: 55~60 bpm) or to a maximum dose of 160 mg/d. Systolic arterial pressure is not less than 90 mm Hg and heart rate is not less than 50 bpm. Other Names: propranolol as the nonselective beta-blockers

Arm

Intervention/Treatment

Experimental: Carvedilol

Carvedilol is started at a dose of 6.25mg/d, and titrated to a maximum dose of 12.5mg/d. Doses are increased 3 days later. Avoid systolic blood pressure <90 mmHg.

Drug: Carvedilol

Carvedilol is started at a dose of 6.25mg/d, and titrated to a maximum dose of 12.5mg/d. Doses are increased 3 days later. Avoid systolic blood pressure <90 mmHg.

Other Names:

carvedilol as the nonselective beta-blockers

Active Comparator: Propranolol

Propranolol is started at a dose of 20 mg/d and the dose will be increased by 10 mg twice a day steps every 2-3 days until the target (heart rate: 55~60 bpm) or to a maximum dose of 160 mg/d. Systolic arterial pressure is not less than 90 mm Hg and heart rate is not less than 50 bpm.

Drug: Propranolol

Other Names:

propranolol as the nonselective beta-blockers

Outcome Measures

Primary Outcome Measures

Variceal rebleeding rate [1 year]
Acute variceal rebleeding rate at 1 year

Secondary Outcome Measures

Further decompensation rate [1 year]
This is a composite outcome that refers to rate of all further liver decompensation events at 1 year, including variceal rebleeding, recurrent or developement of ascites (grade≥2), overt hepatic encephalopathy, spontaneous bacterial peritonitis, acute kidney injury, acute-on-chronic liver failure, and liver-related death.
Adverse events [1 year]
Hypotension (systolic blood pressure <90 mmHg or mean arterial pressure <65 mmHg), development of acute kidney injury/ hepatorenal syndrome, hyponatremia, weakness, shortness of breath, dizziness, gastrointestinal symptoms (nausea, constipation), or sexual and erectile dysfunction.
Transplant-free survival rate [1 year]
The transplant-free survival rate at 1 year

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Between 18 and 80 years old;
With liver cirrhosis diagnosed by previous biopsy or by clinical criteria, and analytical image;
At least 5 days after index variceal bleeding;
Informed consent.

Exclusion Criteria:

Refusal to participate in the study;
Portal hypertension resulting from other causes than liver cirrhosis;
More than 42 days after index variceal bleeding;
Bleeding from cardiofundal gastric varices;
Portal venous thrombosis >50% of the portal vein trunk;
Contraindications to beta-blockers (asthma, chronic obstructive pulmonary disease, atrioventricular block, heart failure, bradycardia with HR ≤40 bpm, arteria hypotension with systolic blood pressure <90 mm Hg, peripheral arterial disease, uncontrolled diabetes);
Prior NSBB+EVL combined treatment, TIPS implantation or surgical shunt as secondary prophylaxis of variceal bledding;
Chronic kidney disease;
Pregnancy or lactation;
Neoplastic disease.