Carvedilol vs. Propranolol in Second Prophylaxis of Variceal Bleeding

NCT ID: NCT05651789

Last Updated: 2022-12-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-31
• Study Completion Date: 2024-12-31

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.

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.

Conditions

Portal Hypertension; Varice Bleed; Cirrhosis, Liver

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Carvedilol

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Propranolol

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

carvedilol as the nonselective beta-blockers; propranolol as the nonselective beta-blockers

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chengdu Shangjin Nanfu Hospital

UNKNOWN

Sponsor Role: collaborator

West China Tianfu Hospital

UNKNOWN

Sponsor Role: collaborator

West China Hospital

OTHER

Sponsor Role: lead

Responsible Party

luo xuefeng

Professor of Hepatology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xuefeng Luo, M.D.

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Central Contacts

Xuefeng Luo, M.D.

Role: CONTACT

Phone: +8613880098212

Email: luo_xuefeng@wchscu.cn

Xiaoze Wang, M.D.

Role: CONTACT

Phone: +8615208207573

Email: wang_xiaoze@wchscu.cn

Other Identifiers

NSBB-RVB

Identifier Type: -

Identifier Source: org_study_id