EVL (Endoscopic Variceal Ligation) Plus Vasoconstrictor vs.Ligation Plus PPI( Proton Pump Inhibitor) in the Control of Acute Esophageal Variceal Bleeding (EVL)

A Randomized, Controlled Trial of Ligation Plus Vasoconstrictor vs.Ligation Plus Proton Pump Inhibitor in the Control of Acute Esophageal Variceal Bleeding

Previous studies showed that combination of endoscopic therapy with vasoconstrictor is better than either vasoconstrictor or endoscopic therapy alone in achieving the successful hemostatsis of acute variceal bleeding. The rationale of using vasoconstrictor is to enhance the efficacy of hemostasis by endoscopic therapy. Nowadays, endoscopic variceal ligation (EVL) has replaced endoscopic injection sclerotherapy (EIS) as the endoscopic treatment of choice in the arresting of acute esophageal variceal hemorrhage. EVL alone can achieve hemotasis up to 97% even in cases of active variceal hemorrhage. However, early rebleeding due to ligation-induced ulcer may be encountered. It appears that prevention of esophageal ulcers and bleeding by a proton pump inhibitor may be more logical than using a vasoconstrictor after cessation of bleeding by EVL.

Study Overview

• Status: Completed
• Conditions: Bleeding; Esophageal Varices
• Intervention / Treatment: Drug: somatostatin or terlipressin; Drug: pantoloc 40 mg

Detailed Description

Previous studies showed that combination of endoscopic therapy with vasoconstrictor is better than either vasoconstrictor or endoscopic therapy alone in achieving the successful hemostatsis of acute variceal bleeding. The rationale of using vasoconstrictor is to enhance the efficacy of hemostasis by endoscopic therapy. Nowadays, endoscopic variceal ligation (EVL) has replaced endoscopic injection sclerotherapy (EIS) as the endoscopic treatment of choice in the arresting of acute esophageal variceal hemorrhage. EVL alone can achieve hemotasis up to 97% even in cases of active variceal hemorrhage. However, early rebleeding due to ligation-induced ulcer may be encountered. It appears that prevention of esophageal ulcers and bleeding by a proton pump inhibitor may be more logical than using a vasoconstrictor after cessation of bleeding by EVL.

Thus, we designed a controlled trial to compare the initial hemostasis, early rebleeding rate in cirrhotic patients presenting with acute variceal bleeding receiving either emergency EVL plus somatostatin infusion or losec infusion for 5 days.

AIMS:

To investigate whether the combination of EVL and somatostatin is superior to the combination of EVL and losec in terms of efficacy in the arresting of acute esophageal variceal bleeding and very early rebleeding.

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 4

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:

• The etiology of portal hypertension is cirrhosis.
• Age ranges between 18-80 y/o.
• Patients presenting with acute esophageal variceal bleeding proven by emergency endoscopy within 12 hours. (Acute esophageal variceal bleeding was defined as: (1) when blood was directly seen by endoscopy to issue from an esophageal varix (active bleeding), or (2) when patients presented with red color signs on their esophageal varices with blood in esophagus or stomach and no other potential site of bleeding identified (inactive bleeding).
• EVL is performed after confirmation of acute esophageal variceal bleeding. Enrollment time: Immediately after EVL is completed and variceal bleeding is arrested.

Exclusion Criteria:

• Association with severe systemic illness, such as sepsis, COPD, uremia
• Association with gastric variceal bleeding
• Failure in the control of bleeding by emergency EVL
• Moribund patients, died within 12 hours of enrollment
• Uncooperative
• Ever received EIS, EVL within one month prior to index bleeding
• Child-Pugh's scores > 13

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EVL + vasoconstrictor; Somatostatin 6mg in 500 cc 5% dextrose, 250μg slow bolus IV infusion followed by 250μg per hour (6mg/ 24 hours) or Terlipressin 2mg bolus was instituted on enrollment followed by 1mg per 6 hours for 5 days. The use of either somatostatin or glypressin was at the discretion of doctors in charge.	Drug: somatostatin or terlipressin; Somatostatin 6mg in 500 cc 5% dextrose, 250μg slow bolus IV infusion followed by 250μg per hour (6mg/ 24 hours) or Terlipressin 2mg bolus was instituted on enrollment followed by 1mg per 6 hours for 5 days. The use of either somatostatin or glypressin was at the discretion of doctors in charge.; Other Names: somatostatin and terlipressin are vasoconstrictors.
Experimental: EVL + PPI; Pantoloc 40 mg intravenously per day was instituted on enrollment and continued for 5	Drug: pantoloc 40 mg; pantoloc iv. infusion per day; Other Names: pantoloc, a proton pump inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success rate of initial hemostasis	Definition of initial hemostasis Initial hemostasis was defined as achieving a 24h bleeding-free period within the first 48h after treatment together with stable vital signs based on Baveno consensus criteria. Very early rebleeding was defined as: UGI bleeding occurred after initial hemostasis and within 5 days after enrollment. UGI bleeding was proven to be from esophageal varices.	5 days
very early rebleeding	Very early rebleeding is defined as episodes of variceal bleeding 48-120 hours after treatment.	48-120 hours after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The amount of blood transfusion within 42 days	The amount of blood transfusion during admission was recorded.	42 days
Mortality	Mortality within 42 days was recorded and compared.	within 42 days
The size and number of ulcers on varices	If p't agrees, a second look endoscopy is performed to detect ulcers.	2 weeks after treatment

Collaborators and Investigators

• Sponsor: National Science Council, Taiwan
• Investigators: Principal Investigator: Gin-Ho Lo, E-DA Hospital

Publications and helpful links

General Publications

• Lo GH, Perng DS, Chang CY, Tai CM, Wang HM, Lin HC. Controlled trial of ligation plus vasoconstrictor versus proton pump inhibitor in the control of acute esophageal variceal bleeding. J Gastroenterol Hepatol. 2013 Apr;28(4):684-9. doi: 10.1111/jgh.12107.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: April 23, 2010
• First Submitted That Met QC Criteria: April 27, 2010
• First Posted (Estimate): April 28, 2010

Study Record Updates

• Last Update Posted (Estimate): April 28, 2010
• Last Update Submitted That Met QC Criteria: April 27, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: control of bleed
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Liver Diseases; Esophageal Diseases; Hypertension, Portal; Hemorrhage; Esophageal and Gastric Varices; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Terlipressin; Vasoconstrictor Agents; Proton Pump Inhibitors; Somatostatin
• Other Study ID Numbers: EVL + PPI; PPI for EVB (Other Grant/Funding Number: Taiwan National Science Council)