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

Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00772057
• Other study ID #: 2008-PHT-02
• Status: Completed
• Phase: N/A
• First received: October 14, 2008
• Last updated: December 18, 2009
• Start date: October 2004
• Est. completion date: October 2008

Study information

• Verified date: October 2008
• Source: Govind Ballabh Pant Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 164
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cirrhosis
• Liver Cirrhosis

Intervention

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.
• Placebo
Placebo tablets given two times daily.

Locations

Country	Name	City	State
India	Department of Gastroenterology, G B Pant Hospital	New Delhi	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Govind Ballabh Pant Hospital

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes