A Trial of Somatostatin With Endoscopic Variceal Ligation (EVL) in Control of Acute Variceal Bleeding (AVB-EVL+S)

A Double Blind Randomized Placebo-Controlled Trial of Somatostatin in Association With Endoscopic Variceal Ligation (EVL) in Control of Acute Variceal Bleeding

Background: Efficacy of endoscopic variceal sclerotherapy in achieving initial control of acute variceal bleeding and five-day haemostasis has been shown to significantly improve when vasoactive drug is added. However, there is limited data whether addition of somatostatin, to endoscopic variceal ligation (EVL) improves the efficacy of EVL.

Aim: To compare EVL plus somatostatin versus EVL plus placebo in control of acute variceal bleeding.

Patients and methods: Consecutive cirrhotic patients with acute variceal bleeding from esophageal varices were enrolled in the trial. After emergency EVL, patients were randomized to receive either somatostatin (250 mcg/hr) or placebo infusion. Primary endpoint was treatment failure within 5 days. Treatment failure was defined as fresh hematemesis ≥2 hour after start of therapy or death.

Study Overview

• Status: Completed
• Conditions: Cirrhosis; Portal Hypertension; Acute Bleeding Esophageal Varices
• Intervention / Treatment: Drug: Somatostatin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110 002
      • Department of Gastroenterology, G B Pant Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of portal hypertension
• Having hematemesis and/or melena within 24 hour prior to admission
• Source of bleeding should be esophageal varices

Exclusion Criteria:

• Non-cirrhotic cause of portal hypertension
• Age <12 or >75 years
• Hepatic encephalopathy grade 3 or 4
• Renal failure with serum creatinine >2 mg/dL
• Any evidence of bleeding from additional source apart from esophageal varices (like gastric varices, portal hypertensive gastropathy, erosions or ulcers including variceal ulcers)
• Patients already on vasoactive drugs like somatostatin or terlipressin during the current episode of bleeding
• Patients already received EVL or EST elsewhere during the current episode of bleeding prior to presenting to our hospital
• Patients with history of surgery for portal hypertension or TIPS
• Concomitant severe cardio-pulmonary disease
• Concomitant malignancy
• HVPG not possible within 24 hrs of presentation
• Patients refusing to participate in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EVL plus Somatostatin; Emergency EVL plus Somatostatin (250 mcg/hr) infusion for 5 days	Drug: Somatostatin; Emergency EVL plus Somatostatin (250 mcg/hr) infusion for 5 days; Other Names: Somatosan; Somastin
Placebo Comparator: EVL plus Placebo; Emergency EVL plus placebo infusion for 5 days	Drug: Placebo; Emergency EVL plus placebo infusion for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment failure	The primary endpoint was treatment failure, defined as the occurrence of any of the following within a period of 120 h (5 days) from the time of admission: (i) Fresh hematemesis ≥2 hr after EVL; or (ii) Death within 5 days.	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-hospital mortality	Death during the same admission to the hospital	During the same admission
Transfusion requirement	Amount of packed cell or FFP infusions received during the hospital stay	During hospital stay
ICU stay in days	Number of dys the patient spent in ICU	During the hospital stay
Drug-related adverse effects	Adverse effects due to somatostatin or placebo infusion	5 days

Collaborators and Investigators

• Sponsor: Govind Ballabh Pant Hospital

Publications and helpful links

General Publications

• Kumar A, Jha SK, Mittal VV, Sharma P, Sharma BC, Sarin SK. Addition of Somatostatin After Successful Endoscopic Variceal Ligation Does not Prevent Early Rebleeding in Comparison to Placebo: A Double Blind Randomized Controlled Trial. J Clin Exp Hepatol. 2015 Sep;5(3):204-12. doi: 10.1016/j.jceh.2015.06.001. Epub 2015 Jun 16.

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

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

Study Record Updates

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

More Information

Terms related to this study

• Keywords: Endoscopic therapy; Octreotide; Variceal bleeding; Somatostatin; Vasoactive drugs; Band ligation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Liver Diseases; Esophageal Diseases; Hemorrhage; Esophageal and Gastric Varices; Hypertension, Portal; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Somatostatin
• Other Study ID Numbers: 2005-PHT-01