A Trial of Nadolol Plus Isosorbide Mononitrate Versus Carvedilol for the Prevention of Variceal Rebleeding

Phase 4

Completed

• Conditions: Variceal Rebleeding
• Interventions: Drug: carvedilol; Drug: nadolol + ISMN

• Registration Number: NCT01103154
• Lead Sponsor: E-DA Hospital

Brief Summary

Carvedilol is shown to be superior to propranolol to reduce the portal pressure. This study was undertaken to compare the effectiveness and complication rates of nadolol and isosorbide mononitrate (ISMN) with carvedilol in the prevention of rebleeding from esophageal varices.

Detailed Description

Bleeding from esophageal varices is a severe complication of portal hypertension. After initial control of acute variceal bleeding, patients have up to a 70% risk of rebleeding. Of those do rebleed, there is a 20%-35% mortality rate. Therefore, preventive procedures are required for patients surviving an episode of acute variceal bleeding. Both endoscopic injection sclerotherapy (EIS) and propranolol have been well documented to be effective for the prevention of variceal rebleeding. In recent years, endoscopic variceal ligation (EVL) has replaced EIS as the endoscopic treatment of choice in the management of bleeding esophageal varices. On the other hand, the addition of isosorbide-5-mononitrate (ISMN) has been shown to be even more effective than propranolol alone in the reduction of portal pressure and in the prevention of variceal rebleeding. A controlled trial showed that the combination of nadolol and ISMN was better than EIS in terms of prevention of variceal rebleeding and complications. The combination of nadolol and ISMN has been shown to be better than EVL in preventing variceal rebleeding. However, our study showed a contradictory result. On the other hand, carvedilol is shown to be superior to propranolol to reduce the portal pressure. This study was undertaken to compare the effectiveness and complication rates of nadolol and ISMN with carvedilol in the prevention of rebleeding from esophageal varices.

Study Timeline

• Study Start: 2005-03
• Primary Completion: 2010-01
• Study Completion: 2010-01
• Study First Submitted: 2010-04-09
• Study First Submitted QC: 2010-04-12
• Study First Posted: 2010-04-14
• Status Verified: 2010-10
• Last Update Submitted: 2010-10-24
• Last Update Posted: 2010-10-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 121

Inclusion Criteria

1. acute or recent bleeding from esophageal varices (defined below),
2. the etiology of portal hypertension was cirrhosis, and
3. age was between 20 and 70 years old.

Exclusion Criteria

1. association with hepatocellular carcinoma or other malignancy,
2. association with cerebral vascular accident, uremia, sepsis or other debilitating disease,
3. had history of gastric variceal bleeding,
4. received beta-blocker within 1 month prior to entry,
5. history of contraindication to the use of beta-blockers, such as asthma, heart failure, atrioventricular block, bradycardia (pulse rate <55/min) or arterial hypotension (systolic blood pressure < 90 mmHg),
6. history of prior shunt operation, TIPS (transjugular intrahepatic portosystemic stent shunt),
7. deep jaundice (serum bilirubin > 10 mg/dl),
8. encephalopathy greater than stage II,
9. failure in control of index variceal bleeding, or
10. refused to participate in the trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Carvedilol	carvedilol	carvedilol 6.25mg per day
N+I	nadolol + ISMN	nadolol 40mg per day, ISMN 10 mg per day

Primary Outcome Measures

Name	Time	Method
variceal rebleeding	2 years	hematemesis or melena,requiring blood transfusion of 2 units or more bleeding source was proven endoscopically to be from esophageal varices

Secondary Outcome Measures

Name	Time	Method
adverse events, mortality	2 years	hypotension, bradycardia, dizziness, impotence, shortness of breath survival