Carvedilol vs. Propranolol in Second Prophylaxis of Variceal Bleeding

Portal Hypertension Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05651789
• Other study ID #: NSBB-RVB
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2023
• Est. completion date: December 2024

Study information

• Verified date: December 2022
• Source: West China Hospital
• Contact: Xuefeng Luo, M.D.
• Phone: +8613880098212
• Email: luo_xuefeng[@]wchscu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 160
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cirrhosis, Liver
• Fibrosis
• Hypertension, Portal
• Liver Cirrhosis
• Portal Hypertension
• Varice Bleed

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
West China Hospital	Chengdu Shangjin Nanfu Hospital, West China Tianfu Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Variceal rebleeding rate	Acute variceal rebleeding rate at 1 year	1 year
Secondary	Further decompensation rate	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.	1 year
Secondary	Adverse events	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.	1 year
Secondary	Transplant-free survival rate	The transplant-free survival rate at 1 year	1 year