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

Variceal Rebleeding Clinical Trial

— Carvedilol  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01103154
• Other study ID #: Carvedilol vs. N+I
• Secondary ID: vghks96CT2-13
• Status: Completed
• Phase: Phase 4
• First received: April 9, 2010
• Last updated: October 24, 2010
• Start date: March 2005
• Est. completion date: January 2010

Study information

• Verified date: October 2010
• Source: E-DA Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Public Health Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Variceal Rebleeding

Intervention

Drug:
• carvedilol
6.25mg per day, increase to 6.25mg bid
• nadolol + ISMN
nadolol 40-80mg ISMN 10-20mg

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
E-DA Hospital	National Science Council, Taiwan

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	variceal rebleeding	hematemesis or melena,requiring blood transfusion of 2 units or more bleeding source was proven endoscopically to be from esophageal varices	2 years	No
Secondary	adverse events, mortality	hypotension, bradycardia, dizziness, impotence, shortness of breath survival	2 years	Yes

External Links

•   National Health Research Institute, Taiwan