Beta-blockers for Prevention Of Growth Of Small Esophageal Varices In Cirrhosis: An Randomized Controlled Trial (RCT)

Early Primary Prophylaxis With Beta-Blockers In Prevention Of Growth Of Small Esophageal Varices In Cirrhosis: A Randomized Controlled Trial

Background and Aims: The efficacy of portal pressure reduction by beta blockers for the management of small (≤5 mm) esophageal varices in patients of cirrhosis is not clear. The present randomized controlled trial aims to address these issues. The investigators also assessed the utility of serial HVPG measurements in these patients.

Patients and Methods: Consecutive patients with cirrhosis with small varices, with no history of variceal bleed, were randomized to receive propranolol or placebo. These patients were further randomized to undergo no HVPG, only baseline HVPG, or serial HVPG measurement. Propranolol was titrated to reduce heart-rate to 55/min.

Study Overview

• Status: Completed
• Conditions: Cirrhosis
• Intervention / Treatment: Drug: Propranolol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 164
• 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: 12 years to 80 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A clinical, radiological or histologic diagnosis of cirrhosis was made
• Age was between 18 and 70 years
• Esophageal varices were small (i.e. ≤5 mm or of grade 1 or 2 according to Conn et al).

Exclusion Criteria:

• Presence of previous variceal bleeding
• Previous medical, surgical or endoscopic treatment for portal hypertension
• Child-Pugh score >13
• Neoplastic disease of any site
• Splenic or portal vein thrombosis
• Concurrent illnesses expected to decrease life expectancy to less than one year
• Pregnancy
• Contraindication to beta-blockers (atrioventricular block, sinus bradycardia with heart rate <50 beats per minute, arterial hypotension with systolic blood pressure <90 mm Hg, heart failure, asthma, peripheral arterial disease, or diabetes needing insulin treatment)
• Concurrent anti-viral treatment during the study period
• Inability to perform follow-up
• Failure to give consent to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo group	Drug: Placebo; Placebo tablets given two times daily.
ACTIVE_COMPARATOR: Propranolol group	Drug: Propranolol; Beta-blocker (propranolol) was started at a dose of 20 mg twice daily. The principle of incremental dosing was used to achieve the target heart rate for propranolol. The dose was increased every alternate day to achieve a target heart rate of 55/min or to the maximal dose to 360 mg/day if the medication was well tolerated and the systolic blood pressure was >90 mm Hg. On the occurrence of intolerable adverse effects, systolic blood pressure <90 mm Hg or pulse rate <55/min, the dose of the medication was decreased step-wise, and eventually stopped if these adverse events persisted. Reintroduction of the medication was attempted if cessation of the medication did not result in improvement of the reported side-effect.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint of the study was the development of large (>5 mm) esophageal varices (grade 3 or 4 by Conn's classification)	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Secondary endpoints were variceal bleeding, death, adverse effects of beta blockers, and hemodynamic response to beta-blocker in patients who underwent serial HVPG	24 months

Collaborators and Investigators

• Sponsor: Govind Ballabh Pant Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (ACTUAL): October 1, 2008
• Study Completion (ACTUAL): October 1, 2008

Study Registration Dates

• First Submitted: October 14, 2008
• First Submitted That Met QC Criteria: October 14, 2008
• First Posted (ESTIMATE): October 15, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): December 21, 2009
• Last Update Submitted That Met QC Criteria: December 18, 2009
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Liver Diseases; Esophageal Diseases; Hypertension, Portal; Fibrosis; Liver Cirrhosis; Esophageal and Gastric Varices; 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: 2008-PHT-02