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

NCT00772057 | Completed

• 1 other identifier: 2008-PHT-02
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cirrhosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (2)

Propranolol group

ACTIVE COMPARATOR

Drug: Propranolol

Placebo group

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Propranolol DRUG

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.

Propranolol group

Placebo DRUG

Placebo tablets given two times daily.

Placebo group

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Govind Ballabh Pant Hospital: lead

Study Sites (1)

Department of Gastroenterology, G B Pant Hospital

New Delhi, National Capital Territory of Delhi, 110002, India

Location

MeSH Terms

Conditions

Fibrosis

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Shiv K Sarin, MD, DM

  G B Pant Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: October 14, 2008
• First Posted: October 15, 2008
• Study Start: October 1, 2004
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: December 21, 2009

Record last verified: 2008-10

Locations

IN (1)