PROPRANOLOL PLUS LIGATION REDUCES RECURRENCE OF ESOPHAGEAL VARICES?

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
DANIELLE ROSSANA DE QUEIROZ MARTINS BONILHA, Federal University of São Paulo
ClinicalTrials.gov Identifier:
NCT01893541
First received: August 4, 2009
Last updated: July 8, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
CIRRHOSIS
ESOPHAGEAL VARICES
Procedure: ENDOSCOPIC BAND LIGATION
Drug: PROPRANOLOL
Device: a multiband ligation device
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: PROPRANOLOL ASSOCIATED WITH ENDOSCOPIC BAND LIGATION REDUCES RECURRENCE OF ESOPHAGEAL VARICES FOR PRIMARY PROPHYLAXIS OF VARICEAL BLEEDING?: A RANDOMIZED CONTROLLED TRIAL

Resource links provided by NLM:


Further study details as provided by Federal University of São Paulo:

Primary Outcome Measures:
  • The primary outcome of this study will be esophageal varices recurrence [ Time Frame: Two years ] [ Designated as safety issue: Yes ]
    Esophageal varices recurrence will be defined as the reappearance of uninterrupted EV of any caliber, with or without red color signs in patients in which varices had been eradicated.


Secondary Outcome Measures:
  • The secondary outcomes of this study will be variceal eradication, bleeding before eradication, mortality and complications. [ Time Frame: two years ] [ Designated as safety issue: Yes ]
    Esophageal varices eradication will be defined as absence of varices in the lower third of the esophagus Bleeding before EV eradication will be defined as any upper GI bleeding before EV obliteration. Bleeding will be considered from unknown origin when it will not possible to perform upper GI endoscopy in the first 48 hours after the bleeding episode; Mortality rate related to treatment will be defined as all cases of death resulting from bleeding due to EV, post-EBL ulceration, gastric varices, portal hypertensive gastropathy or any complication of treatment. Mortality rate non-related to treatment will be defined as death due to other causes; EBL complications will be divided in major (stenosis or esophageal perforation and bleeding due to post-EBL ulceration) and minor (chest pain, dysphagia, transient fever and esophageal ulceration with no bleeding postponing the subsequent treatment session).


Enrollment: 100
Study Start Date: June 2008
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Procedure: 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.
Drug: 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.
Device: a multiband ligation device
Active Comparator: 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.
Procedure: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 78 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01893541

Locations
Brazil
Federal University of São Paulo
São Paulo, Brazil, 04024-002
Sponsors and Collaborators
Federal University of São Paulo
Investigators
Principal Investigator: Danielle Q Bonilha, MD Federal University of São Paulo
  More Information

No publications provided

Responsible Party: DANIELLE ROSSANA DE QUEIROZ MARTINS BONILHA, PhD, Federal University of São Paulo
ClinicalTrials.gov Identifier: NCT01893541     History of Changes
Other Study ID Numbers: DBONILHA
Study First Received: August 4, 2009
Last Updated: July 8, 2013
Health Authority: Brazil: National Health Surveillance Agency

Keywords provided by Federal University of São Paulo:
CIRRHOTIC
VARICEAL BLEEDING
PRIMARY PROPHYLAXIS

Additional relevant MeSH terms:
Esophageal and Gastric Varices
Varicose Veins
Liver Cirrhosis
Fibrosis
Recurrence
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Hypertension, Portal
Liver Diseases
Pathologic Processes
Disease Attributes
Vascular Diseases
Cardiovascular Diseases
Propranolol
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Vasodilator Agents

ClinicalTrials.gov processed this record on July 20, 2014