PROPRANOLOL PLUS LIGATION REDUCES RECURRENCE OF ESOPHAGEAL VARICES?

NCT ID: NCT01893541

Last Updated: 2013-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2011-06-30

Brief Summary

This prospective randomized controlled trial will compare endoscopic band ligation (EBL) with propranolol and EBL alone in primary prophylaxis of variceal bleeding among cirrhotic patients with high-risk varices.

Detailed Description

BACKGROUND AND AIMS

Bleeding from esophagogastric varices (EV) is a major complication of portal hypertension. Beta-blockers are a well-established cornerstone of portal hypertension treatment. Band ligation is the best endoscopic treatment to prevent EV bleeding. The exact benefit of beta-blocker association to band ligation remains to be defined, especially for primary prophylaxis. This prospective randomized controlled trial will compare EBL with propranolol and EBL alone in primary prophylaxis of variceal bleeding among cirrhotic patients with high-risk varices. PATIENTS AND METHODS: The patients with high-risk varices will be randomly allocated to EBL plus propranolol (Group I) or EBL alone (Group II). EBL will be performed at 3-week interval till obliteration of varices. In Group I, incremental dosage of propranolol (sufficient to reduce heart rate to 55 beats/min or 25% reduction from baseline) will be administered and will be continued after obliteration of varices until the end of the study. The follow-up of patients will be 2 years. The primary outcome of this study will be EV recurrence during two years of follow-up. The secondary outcomes will be EV eradication, bleeding before eradication, mortality and complications during the same follow-up.

Conditions

CIRRHOSIS; ESOPHAGEAL VARICES

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

EBL PLUS PROPRANOLOL

The EBL procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices were obliterated. The initial propranolol dose will be orally BID 40 mg, irrespective of patient's weight. The objective of the administration of propranolol will be induce beta-adrenergic blockade evaluated by reduction in heart rate to 55 bpm or a 25% drop in baseline heart rate. A baseline electrocardiogram will be obtained from all patients. The doses will be adjusted during weekly visits until beta-adrenergic blockade. After the adequate dose will be reached, the visits will be scheduled monthly during the first 3 months (until EV eradication) and then at a 3-month interval until the end of follow-up.

Group Type: ACTIVE_COMPARATOR

ENDOSCOPIC BAND LIGATION

Intervention Type: PROCEDURE

The procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. All varices will be treated during the same session. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices will be obliterated.

PROPRANOLOL

Intervention Type: DRUG

The initial propranolol dose will be orally BID 40 mg, irrespective of patient's weight. The objective of the administration of propranolol will be induce beta-adrenergic blockade evaluated by reduction in heart rate to 55 bpm or a 25% drop in baseline heart rate. A baseline electrocardiogram will be obtained from all patients. The doses will be adjusted during weekly visits until beta-adrenergic blockade. After the adequate dose will be reached, the visits will be scheduled monthly during the first 3 months (until EV eradication) and then at a 3-month interval until the end of follow-up.

a multiband ligation device

Intervention Type: DEVICE

ENDOSCOPIC BAND LIGATION

The procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. All varices will be treated during the same session. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices will be obliterated.

Group Type: ACTIVE_COMPARATOR

ENDOSCOPIC BAND LIGATION

Intervention Type: PROCEDURE

The procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. All varices will be treated during the same session. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices will be obliterated.

Interventions

ENDOSCOPIC BAND LIGATION

The procedures will be performed using standard technique with a multiband ligation device. Elastic bands will be placed according to physician decision, starting at esophagogastric junction. All varices will be treated during the same session. Endoscopic band ligation sessions will be repeated at intervals of 3 to 4 weeks until all varices will be obliterated.

Intervention Type: PROCEDURE

PROPRANOLOL

The initial propranolol dose will be orally BID 40 mg, irrespective of patient's weight. The objective of the administration of propranolol will be induce beta-adrenergic blockade evaluated by reduction in heart rate to 55 bpm or a 25% drop in baseline heart rate. A baseline electrocardiogram will be obtained from all patients. The doses will be adjusted during weekly visits until beta-adrenergic blockade. After the adequate dose will be reached, the visits will be scheduled monthly during the first 3 months (until EV eradication) and then at a 3-month interval until the end of follow-up.

Intervention Type: DRUG

a multiband ligation device

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Liver cirrhosis with esophageal varices
• Age between 18 and 78 years
• Accept to participate

Exclusion Criteria

• Portal hypertension by schistosomiasis
• Contraindications for propranolol use
• Do not accept to participate

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 78 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federal University of São Paulo

OTHER

Sponsor Role: lead

Responsible Party

DANIELLE ROSSANA DE QUEIROZ MARTINS BONILHA

PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Danielle Q Bonilha, MD

Role: PRINCIPAL_INVESTIGATOR

Federal University of São Paulo

Locations

Federal University of São Paulo

São Paulo, São Paulo, Brazil

Countries

Brazil

Other Identifiers

DBONILHA

Identifier Type: -

Identifier Source: org_study_id