A Trial of EVL\GVS Alone vs. EVL\GVS Combined Propranolol

Endoscopic Treatment Alone Versus Combined Propranolol and Endoscopic Treatment of Acute Variceal Hemorrhage in Patients With HCC:a Randomized Trial

New strategy to improve the outcomes in patients with HCC and acute variceal bleeding. NSBB added to endoscopic ligation may further reduce rebleeding in cirrhotic patients.

Study Overview

• Status: Unknown
• Conditions: Liver Cirrhosis; Hepatoma
• Intervention / Treatment: Drug: propranolol

Detailed Description

Gastroesophageal vaiceal bleeding is a major complication of portal hypertension. Gastroesophageal variceal bleeding is characteristic of high rebleeding rate and mortality. Thanks to the recent advance of treatment including immediate vasoactive agents (such as somatostatin and vasopressin analogue for acute bleeding), non-selective beta-blocker (NSBB) for prevention of bleeding, prophylactic antibiotics, endoscopic variceal ligation, endoscopic cyanoacrylate injection , combination treatment and general improvement of care for patients with acute variceal bleeding, the rebleeding rate and mortality has a marked reduction. However, hepatocellular carcinoma (HCC) is a distinct group characteristic of very poor prognosis in patients in portal hypertensive patients when compared to those of liver cirrhosis only. Therefore it needs to specially clarify their treatment strategy, particularly in Taiwan, a highly prevalent area of HCC.

In patients of HCC presenting acute variceal bleeding, the rebleeding is around 50% doubled that of patients with cirrhosis only and bleeding mortality also more than 50%. The trend is not changed even after introduction of immediate use of vasoactive agents and endoscopic ligation. The poor outcome is because that HCC patients usually have arterioporal shunting or portal vein thrombosis and higher portal pressure. Moreover, their liver function deteriorated faster. Both high portal pressure and poor liver function are major determinant of hemostatic outcomes. Therefore, it is important to find a new strategy to improve the outcomes in patients with HCC and acute variceal bleeding.NSBB added to endoscopic ligation may further reduce rebleeding in cirrhotic patients. However, whether the hypotensive effect of NSBB is adequate to prevent rebleeding in patients with HCC who usually has higher portal pressure in not known. In addition, concomitant rapid deterioration of liver function might also dampen NSBB effects. Furthermore, due to faster deterioration of general condition, the tolerance of NSBB in these patients might be remarkable and lead to a higher withdrawal rate. Therefore, it is very important to clarify whether there is additive therapeutic effect of NSBB to endoscopic treatment in the 2nd prevention of gastroesophageal variceal bleeding in patients with HCC.

Therefore, the investigators design a study to randomize patients with HCC and acute variceal bleeding to endoscopic treatment alone and combination with endoscopic treatment and NSBB. This is the two years study.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Taipei city, Taiwan
    • Recruiting
    • Veteran General Hospital-Taipei
    • Contact: Ming-Chih Hou, MD; Phone Number: 3763 886-2-28712121; 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 HCC, endoscopically proven gastroesophageal variceal bleeding
• Aged 18 to 80

Exclusion Criteria:

• Had a terminal illness of any major organ system,such as heart failure, kidney failure, COPD

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: EVL\GVS Alone; Endoscopic ligation treatment in the 2nd prevention of gastroesophageal variceal bleeding in patients with HCC
Active Comparator: EVL\GVS Combined Propranolol; Propranolol and endoscopic ligation treatment is used for 2nd prevention of gastroesophageal variceal bleeding in patients with HCC. <EVL\GVS Combined Propranolol>	Drug: propranolol; Starting from 20 mg daily, titrated weekly to decrease heart rate more than 25 % of baseline, administrated during the whole study period; Other Names: Inderal,Cardolol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rebleeding	1 years

Secondary Outcome Measures

Outcome Measure	Time Frame
complication surivial	1 years

Collaborators and Investigators

• Sponsor: Taipei Veterans General Hospital, Taiwan

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): June 1, 2010
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: October 4, 2010
• First Submitted That Met QC Criteria: February 16, 2011
• First Posted (Estimate): February 17, 2011

Study Record Updates

• Last Update Posted (Estimate): June 15, 2011
• Last Update Submitted That Met QC Criteria: June 14, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: non-selective beta-blocker; portal hypertension; Variceal bleeding; rebleeding; endoscopic variceal ligation; hepatocelluar carcinoma
• 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; Vasodilator Agents; Propranolol
• Other Study ID Numbers: V99C1-026; IRB:98-09-09 (Other Identifier: IRB:98-09-09)