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

Study Overview
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Brief Summary
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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.

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

Conditions
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Cirrhosis

Intervention / Treatment
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* Drug: Propranolol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Propranolol group<br> | Drug: Propranolol<br>* 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.<br>|
| Placebo Comparator: Placebo group<br> | Drug: Placebo<br>* Placebo tablets given two times daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |