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

Sponsor

E-DA Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01103154

Collaborator

National Science Council, Taiwan (Other)

121

Enrollment

Arms

58.1

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Variceal Rebleeding	Drug: carvedilol Drug: nadolol + ISMN	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

121 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Controlled Trial of Nadolol Plus Isosorbide Mononitrate vs. Carvedilol for the Prevention of Variceal Rebleeding

Study Start Date :

Mar 1, 2005

Actual Primary Completion Date :

Jan 1, 2010

Study Completion Date :

Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Carvedilol carvedilol 6.25mg per day	Drug: carvedilol 6.25mg per day, increase to 6.25mg bid
Active Comparator: N+I nadolol 40mg per day, ISMN 10 mg per day	Drug: nadolol + ISMN nadolol 40-80mg ISMN 10-20mg

Arm

Intervention/Treatment

Active Comparator: Carvedilol

carvedilol 6.25mg per day

Drug: carvedilol

6.25mg per day, increase to 6.25mg bid

Active Comparator: N+I

nadolol 40mg per day, ISMN 10 mg per day

Drug: nadolol + ISMN

nadolol 40-80mg ISMN 10-20mg

Outcome Measures

Primary Outcome Measures

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

adverse events, mortality [2 years]
hypotension, bradycardia, dizziness, impotence, shortness of breath survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

association with hepatocellular carcinoma or other malignancy,
association with cerebral vascular accident, uremia, sepsis or other debilitating disease,
had history of gastric variceal bleeding,
received beta-blocker within 1 month prior to entry,
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),
history of prior shunt operation, TIPS (transjugular intrahepatic portosystemic stent shunt),
deep jaundice (serum bilirubin > 10 mg/dl),
encephalopathy greater than stage II,
failure in control of index variceal bleeding, or
refused to participate in the trial.