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

This study has been completed.
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by:
E-DA Hospital
ClinicalTrials.gov Identifier:
NCT01103154
First received: April 9, 2010
Last updated: October 24, 2010
Last verified: October 2010
  Purpose

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 Intervention Phase
Variceal Rebleeding
Drug: carvedilol
Drug: nadolol + ISMN
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Controlled Trial of Nadolol Plus Isosorbide Mononitrate vs. Carvedilol for the Prevention of Variceal Rebleeding

Resource links provided by NLM:


Further study details as provided by E-DA Hospital:

Primary Outcome Measures:
  • variceal rebleeding [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    hypotension, bradycardia, dizziness, impotence, shortness of breath survival


Enrollment: 121
Study Start Date: March 2005
Estimated Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Additional Information:
No publications provided

Responsible Party: Gin-Ho Lo, E-DA Hospital
ClinicalTrials.gov Identifier: NCT01103154     History of Changes
Other Study ID Numbers: Carvedilol vs. N+I, vghks96CT2-13
Study First Received: April 9, 2010
Last Updated: October 24, 2010
Health Authority: Taiwan: Public Health Administration

Keywords provided by E-DA Hospital:
beta blocker
variceal rebleeding
efficacy and safety in reducing variceal rebleeding

Additional relevant MeSH terms:
Carvedilol
Isosorbide
Isosorbide Dinitrate
Isosorbide-5-mononitrate
Nadolol
Adrenergic Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Cardiovascular Agents
Diuretics
Diuretics, Osmotic
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Neurotransmitter Agents
Nitric Oxide Donors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sympatholytics
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 23, 2014