Endoscopic Variceal Ligation (EVL)+ Drugs Versus Endoscopic Variceal Ligation (EVL) Alone For Secondary Prophylaxis (Secondary)

Endoscopic Variceal Ligation Plus Propranolol And Isosorbide Mononitrate Versus Endoscopic Variceal Ligation Alone For Secondary Prophylaxis Of Variceal Bleeding: A Randomized Controlled Trial

Background: Both endoscopic variceal ligation (EVL) and propranolol are valuable methods for secondary prophylaxis of variceal bleeding. Addition of ISMN to propranolol improves the efficacy of drug therapy. It is hypothesized that a combination of EVL and portal pressure reducing drugs should significantly be better than EVL alone.

Patients and Methods: Patients with history of variceal bleed were randomized to EVL plus drugs (propranolol and ISMN) or EVL alone. EVL was repeated every 3-4 weeks until variceal eradication. Propranolol dose was adjusted to reduce the resting heart rate to 55 bpm. Dose of ISMN was 40 mg/d. Primary end points were rebleed or death. Secondary end points included complications of portal hypertension and the development of serious adverse effects to therapy.

Study Overview

• Status: Completed
• Conditions: Portal Hypertension
• Intervention / Treatment: Drug: EVL + Propranolol + Isosorbide 5 mononitrate; Other: EVL alone

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110002
      • Department of Gastroenterology, G B Pant Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients presenting to G B Pant Hospital, New Delhi, with history of hematemesis and/or melena and proven to have esophageal varices as the bleeding source on upper GI endoscopy were included in the study.

Exclusion Criteria:

• A history of undergoing endoscopic sclerotherapy (EST), EVL, or cyanoacrylate injection;
• A history of surgery for portal hypertension;
• Coexisting malignancy;
• Severe cardiopulmonary or renal disease;
• A history of severe side-effects or contraindications to beta-blockers like bronchial asthma, uncontrolled diabetes mellitus, heart failure, peripheral vascular disease, prostatic hypertrophy, arterial hypotension (systolic blood pressure < 100 mm Hg), bradycardia (basal heart rate <55 beats per minute), or complete heart block; and
• Refusal to give consent to participate in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EVL + Drugs; Patients randomized to the EVL plus drugs therapy received EVL plus beta-blocker (propranolol) and nitrate (ISMN).	Drug: EVL + Propranolol + Isosorbide 5 mononitrate; Treatment was started with propranolol at a dose of 40 mg twice a day. The heart rate and blood pressure were checked after 12 to 24 hours. The dose of propranolol was increased at increments of 20 to 40 mg per day until the patient achieved a heart rate of 55 bpm, or a maximum dose of 320 mg/day was achieved.ISMN was added at a dose of 10 mg twice a day. The dose was escalated at increments of 10-20 mg/day till a maximum dose of 40 mg/day was reached.
Placebo Comparator: EVL alone; Patients assigned to the EVL group underwent variceal band ligation alone till variceal obliteration.	Other: EVL alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Primary end points of the study were bleeding and death.	During the study period

Secondary Outcome Measures

Outcome Measure	Time Frame
Complications, UGI bleeding due to causes not related to PHT, and adverse effects that required the discontinuation of therapy.	During the study period

Collaborators and Investigators

• Sponsor: Govind Ballabh Pant Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2002
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: October 3, 2008
• First Submitted That Met QC Criteria: October 3, 2008
• First Posted (Estimate): October 6, 2008

Study Record Updates

• Last Update Posted (Estimate): October 6, 2008
• Last Update Submitted That Met QC Criteria: October 3, 2008
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Hypertension, Portal; 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; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Nitric Oxide Donors; Propranolol; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate
• Other Study ID Numbers: 2008-PHT-01