Endoscopic Cyanoacrylate Obliteration vs. Nadolol Treatment in the Prevention of Gastric Variceal Rebleeding (GVO-nadolol)

A Randomized Tril of Endoscopic Cyanoacrylate Obliteration vs. Nadolol

Gastric variceal bleeding has a very high rebleeding rate even after endoscopic variceal injection of cyanoacrylate (GVO) which is considered the first choice of endoscopic treatment. Beta-blocker (BB) is effective to lower portal pressure. We hypothesized combination of GVO and BB can further decrease the rebleeding rate.

Study Overview

• Status: Unknown
• Conditions: Gastric Variceal Bleeding; Liver Cirrhosis and Hepatoma.
• Intervention / Treatment: Drug: Nadolol

Detailed Description

Gastric varies (GV) rarely rupture. However should it occur, the outcome would be worse than rupture of esophageal varies (EV). Rupture of GV is characteristic of a higher rebleeding rate, a requirement for a larger amount of blood transfusion and a higher mortality. Up to date, the treatment of GV bleeding (GVB) is still sub-optimal in contrast to the treatment of EV bleeding. The management of GV has been focused on treatment of acute GVB. Various specific methods are used to control GVB and prevent rebleeding; however they were far from ideal. It is because GV are usually larger vessels formed in deeper submucosa and connect to the spontaneous gastrorenal shunt which creates a fast blood flow. Therefore, voluminous blood in the larger diameter GV leads to exsanguine bleeding when ruptured. A variety of endoscopic methods, which include injection of sclerosants, tissue adhesive (cyanoacrylate), thrombin and ligation with rubber bands, detachable nylon loop and steel snares, are applied to control acute GV bleeding with variable successful rates (50~100%) and rebleeding rates (20~90%). The successful rate of endoscopic cyanoacrylate injection to arrest active GVB is more consistent around 90~100% and rebleeding rate is around 30~40%. The recent International Consensus Meeting endorsed that endoscopic cyanoacrylate injection is the first line treatment for acute GVB. The embolic complications, either septic & aseptic, are not uncommon. Expertise is also required to reduce the embolic complications and instrumental injuries. Therefore, the efficacy of specific treatment for GVB is sub-optimal, consecutive innovation of new methods are required to improve the prognosis of GVB. Non-selective beta-blocker is effective to reduce rebleeding from esophageal varices. However, its effect on gastric variceal hemorrhage has never been proven.

This is an important issues prompted by current portal hypertension experts. We have much experience in the treatment of gastric variceal bleeding and published fruitful results in high ranking journal. Therefore, we design a randomized trial to compare the effect of endoscopic cyanoacrylate injection obliteration versus non-selective beta-blocker in the secondary prevention of acute gastric variceal bleeding.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ming-Chih Hou, MD; Phone Number: 3763 886-2-28712111; Email: mchou@vghtpe.gov.tw
• Study Contact Backup: Name: Han-Chieh Lin, MD; Phone Number: 3349 886-2-28712111; Email: hclin@vghtpe.gov.tw

Study Locations

• China
  • Taiwan
    • Taipei city, Taiwan, China, 11217
      • Recruiting
      • Veteran General Hospital-Taipei
      • Contact: Ming-Chih Hou, MD; Phone Number: 3763 886-2-28712111; Email: mchou@vghtpe.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• clinical diagnosis of liver cirrhosis and/or HCC, endoscopically proven gastric variceal bleeding

Exclusion Criteria:

• younger than 18 y/o or older than 80 y/o, terminal illness, other major systemic disease or malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: G; Endoscopic injection of cyanoacrylate alone
Active Comparator: C; Combination of GVO and nadolol	Drug: Nadolol; Starting from 20 mg daily, titrated weekly to decrease heart rate more than 25 % of baseline, administrated during the whole study period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rebleeding	3 yr

Secondary Outcome Measures

Outcome Measure	Time Frame
Complication Survival	3 yr

Collaborators and Investigators

• Sponsor: Taipei Veterans General Hospital, Taiwan
• Collaborators: National Science Council, Taiwan

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Study Completion (Anticipated): July 1, 2010

Study Registration Dates

• First Submitted: December 2, 2007
• First Submitted That Met QC Criteria: December 2, 2007
• First Posted (Estimate): December 4, 2007

Study Record Updates

• Last Update Posted (Estimate): June 8, 2010
• Last Update Submitted That Met QC Criteria: June 6, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Nadolol
• Other Study ID Numbers: nsc96-2314-B-075-037-MY3; IRB-96-04-01