Beta-Blockers for Prevention Of Growth Of Small Esophageal Varices In Cirrhosis: An Randomized Controlled Trial (RCT) - Full Text View

Sponsored by:	Govind Ballabh Pant Hospital
Information provided by:	Govind Ballabh Pant Hospital
ClinicalTrials.gov Identifier:	NCT00772057

Purpose

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. We 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.

Condition	Intervention
Cirrhosis	Drug: Propranolol Drug: Placebo

MedlinePlus related topics: Cirrhosis Esophagus Disorders Varicose Veins

Drug Information available for: Propranolol Dexpropranolol Propranolol hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Single Blind (Subject), Placebo Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	Early Primary Prophylaxis With Beta-Blockers In Prevention Of Growth Of Small Esophageal Varices In Cirrhosis: A Randomized Controlled Trial

Further study details as provided by Govind Ballabh Pant Hospital:

Primary Outcome Measures:

The primary endpoint of the study was the development of large (>5 mm) esophageal varices (grade 3 or 4 by Conn's classification) [ Time Frame: Study period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Secondary endpoints were variceal bleeding, death, adverse effects of beta blockers, and hemodynamic response to beta-blocker in patients who underwent serial HVPG [ Time Frame: Study period ] [ Designated as safety issue: Yes ]

Enrollment:	164
Study Start Date:	October 2004
Study Completion Date:	June 2007
Primary Completion Date:	June 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Propranolol group: Active Comparator	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 group: Placebo Comparator	Drug: Placebo Placebo tablets given two times daily.

Arms

Assigned Interventions

Propranolol group: Active Comparator

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 group: Placebo Comparator

Drug: Placebo

Placebo tablets given two times daily.

Eligibility

Ages Eligible for Study:	12 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00772057

Locations

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

Sponsors and Collaborators

Govind Ballabh Pant Hospital

Investigators

Principal Investigator:

Shiv K Sarin, MD, DM

G B Pant Hospital

More Information

Responsible Party:	Department of Gastroenterology, G B Pant Hospital, New Delhi, India ( Dr S K Sarin )
Study ID Numbers:	2008-PHT-02
Study First Received:	October 14, 2008
Last Updated:	October 14, 2008
ClinicalTrials.gov Identifier:	NCT00772057
Health Authority:	India: Ministry of Health

Study placed in the following topic categories:

Liver Diseases
Esophageal disorder
Fibrosis
Gastrointestinal Diseases
Liver Cirrhosis
Hypertension, Portal
Portal hypertension

Esophageal varices
Digestive System Diseases
Propranolol
Varicose Veins
Esophageal and Gastric Varices
Esophageal Diseases
Hypertension

Additional relevant MeSH terms:

Neurotransmitter Agents
Vasodilator Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cardiovascular Agents
Antihypertensive Agents

Pharmacologic Actions
Pathologic Processes
Therapeutic Uses
Adrenergic beta-Antagonists
Adrenergic Antagonists
Anti-Arrhythmia Agents

ClinicalTrials.gov processed this record on January 14, 2009