EUS-guided Combined Therapy Versus Beta Blocker Therapy in Primary Prophylaxis o GOV II and IGV I

EUS-guided Combined Therapy of Coiling and 2-octyl-cyanoacrylate Injection With Beta Blocker Therapy Versus Beta Blocker Alone for the Primary Prophylaxis of GOV II and IGV I

The EUS-guided combined therapy of coilingand 2-octyl-cyanoacrylate in patients with gastric varices reduced rebleeding and need for reintervention in comparison to EUS-guided coiling alone.The purpose of this study is to determine the efficacy of the primary prophylaxis of GOV II and IGV I with the EUS combined therapy versus beta blocker therapy in patients GOV II and IGV that have never bleed.

Study Overview

• Status: Unknown
• Conditions: Cirrhosis; GastroIntestinal Bleeding; Gastric Varix
• Intervention / Treatment: Procedure: Coils + Cyanoacrylate Group + beta-blocker; Drug: beta blocker therapy

Detailed Description

Gastric variceal bleeding is a severe condition associated with a high mortality. Bleeding from varices bleeding will be defined as the occurrence of hematemesis and/or melena requiring >2 U of blood or a decrease of 2 gm/dl of hemoglobin if no blood transfusion is given, with the confirmed endocopic visualization of GOV II and IGV I.

The beta blocker therapy is an effective method for the prevention of the first esophageal variceal bleeding; however, the efficacy in preventing first gastric variceal bleeding is controversial.

The investigators aimed to compare the efficacy in preventing the first gastric variceal bleeding in patients with documented GOV II and IGV I.

• Study Type: Interventional
• Enrollment (Anticipated): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ecuador
  • Guayas
    • Guayaquil, Guayas, Ecuador, 090505
      • Recruiting
      • Instituto Ecuatoriano de Enfermedades Digestivas
      • Contact: Carlos Robles-Medranda, M.D.; Phone Number: 593-042109180; Email: carlosoakm@yahoo.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Above 18 years old
• Writeen informed consent provided.
• Proven GV (GOV II or IGV I) on esophagogastroduodenoscopy and EUS.
• Gastric varices with high-risk of bleeding (large diameter, high MELD score, presence of portal hypertensive gastropathy)
• Patient preference for EUS-guided therapy.

Exclusion Criteria:

• Under 18 years old.
• Refuse to sign written informed consent.
• Pregnancy or nursing.
• Previous treatment of gastric varices.
• Non-cirrhotic portal hypertension
• Concurrent hepato-renal syndrome and/or multi-organ failure.
• Proven malignancy including hepatocellular carcinoma
• Platelet count less than 50,000/ml or International Normalized Rate (INR) >2.
• Severe ascites that increases the distance between gastric or duodenal and gallbladder walls.
• Esophageal stricture.
• Uncontrolled coagulopathy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EUS-guided combined therapy; Patients with endoscopic and EUS documented GOV II and IGV I will be included. Procedure will be performed under general anesthesia using a linear array therapeuthic echoendoscope, coils and cyanoacrylate will be injected within the feeder vessel under EUS and fluroscopic guidance.	Procedure: Coils + Cyanoacrylate Group + beta-blocker; EUS-combined coiling and cyanoacrylate injection into the feeder vessel of GOV II and IGV I Patients with Gastric Varices GOV II or IGV I that have never bleed and are of high-risk GV according to Baveno VI consensus will be prophylactically obliterated via the EUS-guided coiling and cyanoacrylate injection. Patients will also be on beta-blocker therapy as indicated in the other group.
Placebo Comparator: Beta Blocker (Propranolol); o Beta-blocker (propranolol) will be started at dose of 20 mg twice daily. The principle of incremental dosing was used to achieve the target heart rate for propranolol. The dose will be 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 will be attempted if cessation of the medication did not result in improvement of the reported side-effect.	Drug: beta blocker therapy; A 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding rate secondary to gastric varices	Number of patients with melena or hematemesis accompanied by Hemoglobin drop > 2g/dL	12 months
Mortality secondary to gastrointestinal bleeding	mortality rate	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of reinterventions	number of endoscopic or endoscopic ultrasound procedures requiered for the management of gastri varices	12 months

Collaborators and Investigators

• Sponsor: Instituto Ecuatoriano de Enfermedades Digestivas
• Investigators: Principal Investigator: Carlos Robles-Medranda, M.D., Instituto Ecuatoriano de Enfermedades Digestivas

Publications and helpful links

General Publications

• Mishra SR, Sharma BC, Kumar A, Sarin SK. Primary prophylaxis of gastric variceal bleeding comparing cyanoacrylate injection and beta-blockers: a randomized controlled trial. J Hepatol. 2011 Jun;54(6):1161-7. doi: 10.1016/j.jhep.2010.09.031. Epub 2010 Nov 5.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: August 30, 2019
• First Posted (Actual): September 3, 2019

Study Record Updates

• Last Update Posted (Actual): October 10, 2019
• Last Update Submitted That Met QC Criteria: October 8, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Hemorrhage; Liver Diseases; Esophageal Diseases; Hypertension, Portal; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic beta-Antagonists
• Other Study ID Numbers: EUS-PP-GV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No