Clinical trial NCT02385422: The Effect of Carvedilol Vs Propranolol in Cirrhotic Patients With Variceal Bleeding
Official title: The Effect of Carvedilol Vs Propranolol in Patients With Cirrhosis Related Esophagogastric Varices After Multiple Endoscopic Treatments For Secondary Prophylaxis:A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Liver Cirrhosis
Esophageal and Gastric Varices
Hemorrhage
Keywords: secondary prophylaxis
Propranolol
Carvedilol
comparative effectiveness research
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2015-03-11
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To compare the efficacy and safety of Carvedilol and Propranolol in patients with cirrhosis-related esophagogastric varices after multiple endoscopic treatments for secondary prophylaxis.

Detailed description: The study is a randomized controlled trial. Patients randomly enter into two treatment groups: 1)the Carvedilol group and 2)the Propranolol group. Treatment allocation is by block randomization, with an equal number for Carvedilol and Propranolol. The results are concealed in opaque envelopes. The dose of non-selective β-blocker(NSBB) is titrated according to systolic arterial blood pressure (ABPsys) and heart rate (HR). Doses are increased every 2-3 days until ABPsys is not less than 90 mm Hg and HR is not less than 55 bpm. Carvedilol is started at a dose of 6.25mg/d, and titrated to a maximum dose of 25mg/d. Patients receiving propranolol start at a dose of 30 mg/day and the dose will be increased to a maximum dose of 160 mg/day. Patients will be followed up with telephone calls every 2 months. After taking these 2 drugs for 6 months, patients come for clinic visits, receiving laboratory tests and endoscopic examinations, and events of primary and secondary outcomes will be analyzed.

Eligibility criteria: Inclusion Criteria:

* age between 18-70 years old;
* cirrhotic patients referred to Zhongshan Hospital with esophagogastric varices confirmed by endoscopy;
* history of variceal bleeding; at least 3 times of endoscopic treatment;
* with 1) mild esophageal varices;2) gastric varices with a diameter less than 5mm; or 3) variceal eradication at the time of recruiting.

Exclusion Criteria:

Patients are excluded when they have

* episodes of variceal bleeding after the last endoscopic treatment;
* diagnosis of hepatic cellular carcinoma;
* severe systemic diseases;
* refractory ascites;
* contraindication to Carvedilol or Propranolol, such as: asthma, chronic obstructive pulmonary disease, allergic rhinitis, New York Heart Association IV chronic heart failure, atrioventricular blockade, severe bradycardia(HR\<50bpm), sick sinus syndrome, cardiogenic shock, severe hypotension(ABPsys\<85mmHg);
* previous and continued use of β-blockers;
* Child -Pugh Class C.

Primary outcomes:
measure: Endoscopic Retreatment
timeFrame: 6 months
Secondary outcomes:
measure: Rebleeding rate
timeFrame: 6 months
measure: Mortality rate
timeFrame: 6 months
measure: Adverse events
timeFrame: 6 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Shiyao Chen, Professor
role: STUDY_DIRECTOR
References: