The Effect of Carvedilol VS Endoscopic Therapy in Primary Prophylaxis of High-risk Esophageal Gastric Variceal Bleeding

Study Overview
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Brief Summary
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To compare the efficacy and safety of Carvedilol and endoscopic therapy in Primary Prophylaxis of High-risk Esophageal Gastric Variceal Bleeding.

Detailed Description
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The study is a randomized controlled trial. Patients randomly enter into two treatment groups: 1)the Carvedilol group and 2)the endoscopy group. Treatment allocation is by block randomization, with an two-to-one ratio for Carvedilol and endoscopy. The results are concealed in opaque envelopes. The dose of Carvedilol is titrated according to systolic arterial blood pressure (ABPsys) and heart rate (HR). Doses are increased every 7 days until ABPsys is not less than 95 mm Hg and HR is not less than 55 bpm. Carvedilol is started at a dose of 6.25 mg/d, and titrated to a maximum dose of 12.5 mg/d. Patients receiving endoscopic therapy every 4 weeks until eradication of varices. Patients will come for clinic visit every 6 months, receiving laboratory tests and endoscopic examinations, and events of primary and secondary outcomes will be analyzed.

Official Title
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Primary Prophylaxis of High-risk Esophageal Gastric Variceal Bleeding Comparing Carvedilol and Endoscopic Therapy: A Multicenter Randomized Controlled Trial

Conditions
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Liver Cirrhosis, Esophageal and Gastric Varices

Intervention / Treatment
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* Drug: Carvedilol
* Device: endoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: the presence of severe esophageal and gastric varices at upper gastrointestinal endoscopy without a previous haemorrhage a diagnosis of liver cirrhosis based on histology, clinical or imaging manifestation Exclusion Criteria: age greater than 80 years old or younger than 18 years old non-cirrhotic portal hypertension contraindications to NSBB including bronchospasm, severe bradycardia, severe heart failure, acute pulmonary edema, atrioventricular block and so on ABPsys less than 95 mmHg or HR less than 50 bpm prior treatment for prevention of bleeding from EGV presence of spontaneous bacterial peritonitis or other severe infections presence of hepatorenal syndrome uncontrolled hepatic encephalopathy presence of refractory ascites pregnancy presence of portosystemic shunt or portal cavernous transformation refusal to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carvedilol<br>Carvedilol，6.25mg-12.5mg/d,oral,6-36 months | Drug: Carvedilol<br>* Carvedilol is started at a dose of 6.25 mg/d, and titrated to a maximum dose of 12.5 mg/d.Doses are increased every 7 days until ABPsys is not less than 95 mm Hg and HR is not less than 55 bpm.<br>* Other names: LvDao;|
| Active Comparator: endoscopy<br>endoscopy，every 4 weeks until eradication of varices | Device: endoscopy<br>* Patients receiving endoscopic therapy (either endoscopic ligation or cyanoacrylate injection) every 4 weeks until eradication of varices.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding rate | The investigators observe the variceal bleeding events during the study | through study completion，an average of 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate | The investigators observe the mortality events during the study due to variceal bleeding, hepatic encephalopathy, liver failure, hepatic cellular carcinoma, hepatic-renal syndrome and spontaneous bacterial peritonitis. | through study completion，an average of 18 months | 
| Adverse events | The investigators observe any severe adverse events caused by drug or endoscopic treatment. | through study completion，an average of 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophageal and Gastric Varices, Primary Prophylaxis, Carvedilol, Endoscopy