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

Phase 4

Completed

• Conditions: Esophageal Varices; Bleeding
• Interventions: Drug: pantoloc 40 mg; Drug: somatostatin or terlipressin

• Registration Number: NCT01112852
• Lead Sponsor: National Science Council, Taiwan

Brief Summary

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.

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 Timeline

• Study Start: 2006-12
• Status Verified: 2010-04
• Primary Completion: 2010-04
• Study Completion: 2010-04
• Study First Submitted: 2010-04-23
• Study First Submitted QC: 2010-04-27
• Last Update Submitted: 2010-04-27
• Study First Posted: 2010-04-28
• Last Update Posted: 2010-04-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 118

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EVL + PPI	pantoloc 40 mg	Pantoloc 40 mg intravenously per day was instituted on enrollment and continued for 5
EVL + vasoconstrictor	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.

Primary Outcome Measures

Name	Time	Method
Success rate of initial hemostasis	5 days	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.
very early rebleeding	48-120 hours after treatment	Very early rebleeding is defined as episodes of variceal bleeding 48-120 hours after treatment.

Secondary Outcome Measures

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