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Carvedilol vs. Propranolol in Second Prophylaxis of Variceal Bleeding

Primary Purpose

Portal Hypertension, Varice Bleed, Cirrhosis, Liver

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Carvedilol
Propranolol
Sponsored by
West China Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Portal Hypertension

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Carvedilol

    Propranolol

    Arm Description

    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 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.

    Outcomes

    Primary Outcome Measures

    Variceal rebleeding rate
    Acute variceal rebleeding rate at 1 year

    Secondary Outcome Measures

    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.
    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.
    Transplant-free survival rate
    The transplant-free survival rate at 1 year

    Full Information

    First Posted
    November 21, 2022
    Last Updated
    December 14, 2022
    Sponsor
    West China Hospital
    Collaborators
    Chengdu Shangjin Nanfu Hospital, West China Tianfu Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05651789
    Brief Title
    Carvedilol vs. Propranolol in Second Prophylaxis of Variceal Bleeding
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 2023 (Anticipated)
    Primary Completion Date
    December 2024 (Anticipated)
    Study Completion Date
    December 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    West China Hospital
    Collaborators
    Chengdu Shangjin Nanfu Hospital, West China Tianfu Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Portal Hypertension, Varice Bleed, Cirrhosis, Liver

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    160 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Carvedilol
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Propranolol
    Arm Type
    Active Comparator
    Arm Description
    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
    Intervention Name(s)
    Carvedilol
    Other Intervention Name(s)
    carvedilol as the nonselective beta-blockers
    Intervention Description
    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
    Intervention Name(s)
    Propranolol
    Other Intervention Name(s)
    propranolol as the nonselective beta-blockers
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Variceal rebleeding rate
    Description
    Acute variceal rebleeding rate at 1 year
    Time Frame
    1 year
    Secondary Outcome Measure Information:
    Title
    Further decompensation rate
    Description
    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.
    Time Frame
    1 year
    Title
    Adverse events
    Description
    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.
    Time Frame
    1 year
    Title
    Transplant-free survival rate
    Description
    The transplant-free survival rate at 1 year
    Time Frame
    1 year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xuefeng Luo, M.D.
    Phone
    +8613880098212
    Email
    luo_xuefeng@wchscu.cn
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xiaoze Wang, M.D.
    Phone
    +8615208207573
    Email
    wang_xiaoze@wchscu.cn
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Xuefeng Luo, M.D.
    Organizational Affiliation
    West China Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Carvedilol vs. Propranolol in Second Prophylaxis of Variceal Bleeding

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