Rebleeding of Portal Hypertension in Liver CirrhosisPhase 4NCT07352228
Carvedilol vs. Propranolol for Preventing Rebleeding After Endoscopic Treatment of Cirrhotic Varices
A Phase 4 study testing Propranolol and Carvedilol in people with Rebleeding of Portal Hypertension in Liver Cirrhosis and Propranolol, run by Xijing Hospital at 1 site in China.
Trial summary
Cirrhosis is a serious liver disease where scar tissue replaces healthy liver tissue, often leading to portal hypertension-a condition where blood pressure in the liver's blood vessels rises. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rebleeding of Portal Hypertension in Liver Cirrhosis, Propranolol, Carvedilol
- What is being tested?
- Propranolol and Carvedilol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 350 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2026to 30 Oct 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with cirrhosis (based on previous liver biopsy or typical clinical features) with a history of variceal bleeding, and the most recent bleeding occurred 6-30 days before enrollment
- Aged 18-75 years (based on ID card age on the enrollment date)
- Voluntarily signs the informed consent form and can cooperate with full-course follow-up and related examinations
Who cannot join
- Non-cirrhotic portal hypertension (eg:Budd-Chiari syndrome, extrahepatic portal vein obstruction, idiopathic portal hypertension)
- Contraindications to non-selective beta-blockers (NSBBs) (eg:asthma, insulin-dependent diabetes mellitus, peripheral vascular disease)
- Malignant tumors (including hepatocellular carcinoma) or other life-shortening diseases (expected survival<1 year), including severe cardio-cerebrovascular diseases (eg:severe heart failure, bedridden status after cerebral infarction, cerebral hemorrhage), end-stage renal disease (requiring dialysis), severe pulmonary diseases (eg:acute exacerbation of chronic obstructive pulmonary disease, pulmonary fibrosis)etc
- Previous shunt or devascularization surgery, oral NSBBs, and/or endoscopic treatment for preventing recurrent variceal bleeding
- Pregnant or lactating women (female subjects must undergo a pregnancy test before enrollment; positive cases are excluded; lactating women can only enroll after stopping breastfeeding)
- Allergies to carvedilol, propranolol, or endoscopic treatment-related drugs (eg:local anesthetics, tissue adhesives)
- Severe hepatic and renal insufficiency: Child-Pugh class C with a score > 12, or MELD score > 30; serum creatinine > 221 μmol/L (2.5 mg/dl) with estimated glomerular filtration rate (eGFR) < 30 ml/(min·1.73m²)
- Severe coagulation disorders: prothrombin time (PT) prolonged by > 10 seconds, or international normalized ratio (INR) > 2.5 without effective correction measures
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Carvedilol vs. Propranolol for Preventing Rebleeding After Endoscopic Treatment of Cirrhotic Varices: A Single-Center Randomized Controlled Trial
Cirrhosis is a serious liver disease where scar tissue replaces healthy liver tissue, often leading to portal hypertension-a condition where blood pressure in the liver's blood vessels rises. A life-threatening complication of this is variceal bleeding, which happens when swollen veins (varices) in the esophagus or stomach rupture. Around 30% of patients die during their first variceal bleeding episode, and 60-70% of survivors face a high risk of rebleeding, making secondary prevention crucial for improving outcomes.
Current guidelines recommend combining non-selective beta-blockers (a type of blood pressure medication) with endoscopic ligation (a procedure to tie off swollen veins) as the first-line treatment to prevent recurrent variceal bleeding. Propranolol is a commonly used non-selective beta-blocker, but it only works for 30-50% of patients by effectively reducing liver vein pressure. Carvedilol, a newer generation of this type of drug, is more potent at lowering liver vein pressure and is recommended for preventing first-time variceal bleeding. However, there is limited research on its effectiveness and safety for preventing recurrent bleeding, and concerns exist that it may cause low blood pressure, which could worsen conditions like ascites (fluid buildup in the abdomen) in some patients.
Read more
This study aims to answer a key question: Is combining endoscopic treatment with carvedilol more effective and safe than combining endoscopic treatment with propranolol for preventing recurrent bleeding in cirrhosis patients who have already experienced variceal bleeding? The research hypothesis is that carvedilol will reduce the rate of recurrent bleeding more effectively than propranolol when both are used alongside endoscopic treatment, while having a similar or acceptable safety profile.
This is a single-center randomized controlled trial conducted by the First Affiliated Hospital of Air Force Medical University, lasting 3 years (from October 2025 to October 2028). The investigators plan to recruit 350 eligible patients, aged 18-75, who have been diagnosed with cirrhosis, have a history of variceal bleeding (with the most recent episode 6-30 days before enrollment), and voluntarily agree to participate and complete follow-up. These patients will be randomly divided into two groups in a 1:1 ratio. Both groups will receive endoscopic treatment first; one group will then take propranolol, and the other will take carvedilol, with dosage adjustments based on their heart rate, blood pressure, and tolerance.
Throughout the study, the investigators will closely monitor patients for recurrent bleeding (the main measure of effectiveness) and other outcomes like disease progression, death, new or worsening ascites, liver encephalopathy (brain dysfunction due to liver disease), and changes in quality of life. The investigators will also track side effects of the drugs and complications from the endoscopic procedure to assess safety.
The results of this study will help clarify whether carvedilol can become a better choice than propranolol for preventing recurrent variceal bleeding, providing more reliable treatment guidance for cirrhosis patients and potentially improving their survival rates and quality of life.
- Being tested
- Propranolol, Carvedilol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropranololDrug
Also called inderol
Oral propranolol is administered within 24-72 hours after enrollment, with an initial dose of 10-20 mg twice daily. Heart rate is monitored 12-24 hours after medication initiation. Target heart rate: 50-60 beats/min or 75% of the baseline value. If the target heart rate is achieved without adverse reactions, the current dose is maintained. If not achieved without adverse reactions, the dose is gradually increased by 10-20 mg/day (divided into 2 doses; e.g., 20 mg/day can be increased to 30-40 mg/day, still twice daily). Maximum dose: 320 mg/day. If the maximum dose is reached without achieving the target heart rate, the maximum dose is maintained. If adverse reactions (e.g., bradycardia, hypotension) occur, the dose is immediately reduced to the maximum tolerated dose; intolerable cases discontinue medication and are recorded as adverse events. During the first 3 months of dose adjustment, heart rate is checked monthly; after dose stabilization, it is checked every 3 months.
CarvedilolDrug
Oral carvedilol is administered within 24-72 hours after enrollment, with an initial dose of 6.25 mg once daily. After 3 days to 1 week, if systolic blood pressure ≥ 90 mmHg, heart rate ≥ 55 beats/min, and no significant adverse reactions, the dose is increased to 6.25 mg twice daily. If heart rate < 55 beats/min, systolic blood pressure < 90 mmHg, or significant adverse reactions occur, the dose is reduced to 6.25 mg once daily; intolerable cases discontinue medication and are recorded as adverse events. Maximum dose: 12.5 mg/day (25 mg/day may be considered for patients with persistent hypertension after physician evaluation, with close blood pressure monitoring). During the first 3 months of dose adjustment, heart rate and blood pressure are checked monthly; after dose stabilization, they are checked every 3 months. Medication adherence is monitored via telephone follow-up.
| Study group | Role | What they receive |
|---|---|---|
| Carvedilol group | Active comparator | Oral carvedilol is administered within 24-72 hours after enrollment, with an initial dose of 6.25 mg once daily. After 3 days to 1 week, if systolic blood pressure ≥ 90 mmHg, heart rate ≥ 55 beats/min, and no significant adverse reactions, the dose is increased to 6.25 mg twice daily. If heart rate < 55 beats/min, systolic blood pressure < 90 mmHg, or significant adverse reactions occur, the dose is reduced to 6.25 mg once daily; intolerable cases discontinue medication and are recorded as adverse events. Maximum dose: 12.5 mg/day (25 mg/day may be considered for patients with persistent hypertension after physician evaluation, with close blood pressure monitoring). During the first 3 months of dose adjustment, heart rate and blood pressure are checked monthly; after dose stabilization, they are checked every 3 months. Medication adherence is monitored via telephone follow-up. Receives: Drug: Carvedilol |
| Propranolol Group | Placebo comparator | Oral propranolol is administered within 24-72 hours after enrollment, with an initial dose of 10-20 mg twice daily. Heart rate is monitored 12-24 hours after medication initiation. Target heart rate: 50-60 beats/min or 75% of the baseline value. If the target heart rate is achieved without adverse reactions, the current dose is maintained. If not achieved without adverse reactions, the dose is gradually increased by 10-20 mg/day (divided into 2 doses; e.g., 20 mg/day can be increased to 30-40 mg/day, still twice daily). Maximum dose: 320 mg/day. If the maximum dose is reached without achieving the target heart rate, the maximum dose is maintained. If adverse reactions (e.g., bradycardia, hypotension) occur, the dose is immediately reduced to the maximum tolerated dose; intolerable cases discontinue medication and are recorded as adverse events. During the first 3 months of dose adjustment, heart rate is checked monthly; after dose stabilization, it is checked every 3 months. Receives: Drug: Propranolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause recurrent bleeding
All-cause rebleeding is the primary efficacy endpoint of this trial (per Baveno V consensus), referring to recurrent bleeding (melena or hematemesis) in cirrhotic portal hypertension patients with prior variceal bleeding-regardless of the new bleeding cause. It is defined by any of the following: hospitalization for bleeding, need for blood transfusion, hemoglobin decrease ≥ 3 g/dl, or death within 6 weeks of recurrence. Timing-wise, early rebleeding occurs 72 hours-6 weeks after initial bleeding control, and delayed rebleeding after 6 weeks. This indicator reflects the study treatments' (endoscopic ligation + carvedilol/propranolol) preventive effect on all bleeding events in cirrhotic patients.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2026
- Study start1 Jan 2026 (estimated)
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rebleeding of Portal Hypertension in Liver CirrhosisStudies of the same condition, open and under way.
- More trials run by Xijing HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xijing Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07352228
- Sponsor's protocol ID
- XJLL-KY-20252468
- Status last verified
- Dec 2025
- First submitted
- 25 Dec 2025
- Last updated
- 20 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carvedilol vs. Propranolol for Preventing Rebleeding After Endoscopic Treatment of Cirrhotic Varices: A Single-Center Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07352228
- Acronym / sponsor ID
- XJLL-KY-20252468
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Xijing HospitalUniversity, hospital or other
- Study start
- 1 Jan 2026 (estimated)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Oct 2028 (estimated)
- First posted
- 20 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cirrhosis is a serious liver disease where scar tissue replaces healthy liver tissue, often leading to portal hypertension-a condition where blood pressure in the liver's blood vessels rises. A life-threatening complication of this is variceal bleeding, which happens when swollen veins (varices) in the esophagus or stomach rupture. Around 30% of patients die during their first variceal bleeding episode, and 60-70% of survivors face a high risk of rebleeding, making secondary prevention crucial for improving outcomes.
Current guidelines recommend combining non-selective beta-blockers (a type of blood pressure medication) with endoscopic ligation (a procedure to tie off swollen veins) as the first-line treatment to prevent recurrent variceal bleeding. Propranolol is a commonly used non-selective beta-blocker, but it only works for 30-50% of patients by effectively reducing liver vein pressure. Carvedilol, a newer generation of this type of drug, is more potent at lowering liver vein pressure and is recommended for preventing first-time variceal bleeding. However, there is limited research on its effectiveness and safety for preventing recurrent bleeding, and concerns exist that it may cause low blood pressure, which could worsen conditions like ascites (fluid buildup in the abdomen) in some patients.
This study aims to answer a key question: Is combining endoscopic treatment with carvedilol more effective and safe than combining endoscopic treatment with propranolol for preventing recurrent bleeding in cirrhosis patients who have already experienced variceal bleeding? The research hypothesis is that carvedilol will reduce the rate of recurrent bleeding more effectively than propranolol when both are used alongside endoscopic treatment, while having a similar or acceptable safety profile.
This is a single-center randomized controlled trial conducted by the First Affiliated Hospital of Air Force Medical University, lasting 3 years (from October 2025 to October 2028). The investigators plan to recruit 350 eligible patients, aged 18-75, who have been diagnosed with cirrhosis, have a history of variceal bleeding (with the most recent episode 6-30 days before enrollment), and voluntarily agree to participate and complete follow-up. These patients will be randomly divided into two groups in a 1:1 ratio. Both groups will receive endoscopic treatment first; one group will then take propranolol, and the other will take carvedilol, with dosage adjustments based on their heart rate, blood pressure, and tolerance.
Throughout the study, the investigators will closely monitor patients for recurrent bleeding (the main measure of effectiveness) and other outcomes like disease progression, death, new or worsening ascites, liver encephalopathy (brain dysfunction due to liver disease), and changes in quality of life. The investigators will also track side effects of the drugs and complications from the endoscopic procedure to assess safety.
The results of this study will help clarify whether carvedilol can become a better choice than propranolol for preventing recurrent variceal bleeding, providing more reliable treatment guidance for cirrhosis patients and potentially improving their survival rates and quality of life.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carvedilol group | Active comparator | Drug: CarvedilolOral carvedilol is administered within 24-72 hours after enrollment, with an initial dose of 6.25 mg once daily. After 3 days to 1 week, if systolic blood pressure ≥ 90 mmHg, heart rate ≥ 55 beats/min, and no significant adverse reactions, the dose is increased to 6.25 mg twice daily. If heart rate < 55 beats/min, systolic blood pressure < 90 mmHg, or significant adverse reactions occur, the dose is reduced to 6.25 mg once daily; intolerable cases discontinue medication and are recorded as adverse events. Maximum dose: 12.5 mg/day (25 mg/day may be considered for patients with persistent hypertension after physician evaluation, with close blood pressure monitoring). During the first 3 months of dose adjustment, heart rate and blood pressure are checked monthly; after dose stabilization, they are checked every 3 months. Medication adherence is monitored via telephone follow-up. |
| Propranolol Group | Placebo comparator | Drug: PropranololOral propranolol is administered within 24-72 hours after enrollment, with an initial dose of 10-20 mg twice daily. Heart rate is monitored 12-24 hours after medication initiation. Target heart rate: 50-60 beats/min or 75% of the baseline value. If the target heart rate is achieved without adverse reactions, the current dose is maintained. If not achieved without adverse reactions, the dose is gradually increased by 10-20 mg/day (divided into 2 doses; e.g., 20 mg/day can be increased to 30-40 mg/day, still twice daily). Maximum dose: 320 mg/day. If the maximum dose is reached without achieving the target heart rate, the maximum dose is maintained. If adverse reactions (e.g., bradycardia, hypotension) occur, the dose is immediately reduced to the maximum tolerated dose; intolerable cases discontinue medication and are recorded as adverse events. During the first 3 months of dose adjustment, heart rate is checked monthly; after dose stabilization, it is checked every 3 months. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosed with cirrhosis (based on previous liver biopsy or typical clinical features) with a history of variceal bleeding, and the most recent bleeding occurred 6-30 days before enrollment
- Aged 18-75 years (based on ID card age on the enrollment date)
- Voluntarily signs the informed consent form and can cooperate with full-course follow-up and related examinations
Key exclusion criteria (8 listed)
- Non-cirrhotic portal hypertension (eg:Budd-Chiari syndrome, extrahepatic portal vein obstruction, idiopathic portal hypertension)
- Contraindications to non-selective beta-blockers (NSBBs) (eg:asthma, insulin-dependent diabetes mellitus, peripheral vascular disease)
- Malignant tumors (including hepatocellular carcinoma) or other life-shortening diseases (expected survival<1 year), including severe cardio-cerebrovascular diseases (eg:severe heart failure, bedridden status after cerebral infarction, cerebral hemorrhage), end-stage renal disease (requiring dialysis), severe pulmonary diseases (eg:acute exacerbation of chronic obstructive pulmonary disease, pulmonary fibrosis)etc
- Previous shunt or devascularization surgery, oral NSBBs, and/or endoscopic treatment for preventing recurrent variceal bleeding
- Pregnant or lactating women (female subjects must undergo a pregnancy test before enrollment; positive cases are excluded; lactating women can only enroll after stopping breastfeeding)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PropranololAlso: inderolOral propranolol is administered within 24-72 hours after enrollment, with an initial dose of 10-20 mg twice daily. Heart rate is monitored 12-24 hours after medication initiation. Target heart rate: 50-60 beats/min or 75% of the baseline value. If the target heart rate is achieved without adverse reactions, the current dose is maintained. If not achieved without adverse reactions, the dose is gradually increased by 10-20 mg/day (divided into 2 doses; e.g., 20 mg/day can be increased to 30-40 mg/day, still twice daily). Maximum dose: 320 mg/day. If the maximum dose is reached without achieving the target heart rate, the maximum dose is maintained. If adverse reactions (e.g., bradycardia, hypotension) occur, the dose is immediately reduced to the maximum tolerated dose; intolerable cases discontinue medication and are recorded as adverse events. During the first 3 months of dose adjustment, heart rate is checked monthly; after dose stabilization, it is checked every 3 months. | Drug | Propranolol Group |
| CarvedilolOral carvedilol is administered within 24-72 hours after enrollment, with an initial dose of 6.25 mg once daily. After 3 days to 1 week, if systolic blood pressure ≥ 90 mmHg, heart rate ≥ 55 beats/min, and no significant adverse reactions, the dose is increased to 6.25 mg twice daily. If heart rate < 55 beats/min, systolic blood pressure < 90 mmHg, or significant adverse reactions occur, the dose is reduced to 6.25 mg once daily; intolerable cases discontinue medication and are recorded as adverse events. Maximum dose: 12.5 mg/day (25 mg/day may be considered for patients with persistent hypertension after physician evaluation, with close blood pressure monitoring). During the first 3 months of dose adjustment, heart rate and blood pressure are checked monthly; after dose stabilization, they are checked every 3 months. Medication adherence is monitored via telephone follow-up. | Drug | Carvedilol group |
Primary outcome
All-cause recurrent bleeding
Time frame: Up to 12 months
All-cause rebleeding is the primary efficacy endpoint of this trial (per Baveno V consensus), referring to recurrent bleeding (melena or hematemesis) in cirrhotic portal hypertension patients with prior variceal bleeding-regardless of the new bleeding cause. It is defined by any of the following: hospitalization for bleeding, need for blood transfusion, hemoglobin decrease ≥ 3 g/dl, or death within 6 weeks of recurrence. Timing-wise, early rebleeding occurs 72 hours-6 weeks after initial bleeding control, and delayed rebleeding after 6 weeks. This indicator reflects the study treatments' (endoscopic ligation + carvedilol/propranolol) preventive effect on all bleeding events in cirrhotic patients.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Propranolol and Carvedilol in people with Rebleeding of Portal Hypertension in Liver Cirrhosis and Propranolol, run by Xijing Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause recurrent bleeding (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026.