Interventional Devascularization Plus HVPG-Guided Carvedilol Therapy vs TIPS

February 2, 2020 updated by: Tie Jun, Air Force Military Medical University, China

Interventional Devascularization Plus HVPG-Guided Carvedilol Therapy vs TIPS for the Prevention of Gastric Variceal Rebleeding in Patients With Liver Cirrhosis: A Prospective, Randomized, Controlled Trial

Gastric varices (GV) are present in around 20% of patients with cirrhosis. Bleeding from GV accounts for 10-20% of all variceal bleeding. For the prevention of gastric variceal bleeding, TIPS or BRTO as firstline treatments were suggested.

No randomized trials have compared BRTO with other therapies. BRTO and its variations might increase portal pressure and might worsen complications, such as ascites or bleeding from EV. In this regard, if NSBB is combined with BRTO and its variations (we called interventional devascularization) for those HVPG responders, the drawbacks of interventional devascularization might be overcome. Therefore, the investigators conducted this RCT to compare the effectiveness and safety of TIPS with those of interventional devascularization in the prevention of rebleeding from gastric varices.

Study Overview

Detailed Description

Gastric varices (GV) are present in around 20% of patients with cirrhosis. Bleeding from GV accounts for 10-20% of all variceal bleeding. GV are classified according to their location in the stomach and their relationship with esophageal varices (EV). Accordingly, GV are divided into gastroesophageal varices (GOV) and isolated gastric varices (IGV) . The management of type 1 GOV, which extend from the esophagus along the lesser curvature of the stomach, is similar to the management of EV. Historically, bleeding from type 2 GOV (i.e. GOV extending into the fundus), type 1 IGV (i.e. located in the fundus) and type 2 IGV (i.e. located anywhere in the stomach), is considered to be more severe and difficult to treat than EV bleeding. Few studies, mostly retrospective and uncontrolled, have focused on the management of non-GOV1 GV, and the optimal treatment remains controversial.

For the prevention of gastric variceal bleeding, treatment principles can be classified into two categories: decreasing portal pressure and obstructing GEV. Methods for decreasing portal pressure include medications (NSBB), radiological intervention (TIPS) and surgery. In contrast, methods for treating the obstruction of GEV include endoscopic approaches (EVL, EIS) or radiological intervention (such as BRTO). Recent portal hypertensive bleeding suggested TIPS or BRTO as firstline treatments in the prevention of rebleeding.

BRTO is a procedure for treatment of fundal varices associated with a large gastro-/splenorenal collateral. The technique involves retrograde cannulation of the left renal vein by the jugular or femoral vein, followed by balloon occlusion and slow infusion of sclerosant to obliterate the gastro-/splenorenal collateral and fundal varices. Several variations of the technique exist, such as balloon-occluded antegrade transvenous obliteration or occlusion of the collateral by the placement of a vascular plug or coils. BRTO has the theoretical advantage over TIPS that it does not divert portal blood inflow from the liver. On the other hand, BRTO and its variations might increase portal pressure and might worsen complications, such as ascites or bleeding from EV. In this regard, if NSBB is combined with BRTO and its variations (we called interventional devascularization) for those HVPG responders, the drawbacks of interventional devascularization might be overcome.

Therefore, the investigators conducted this RCT to compare the effectiveness and safety of TIPS with those of interventional devascularization in the prevention of rebleeding from gastric varices.

Study Type

Interventional

Enrollment (Anticipated)

212

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Liver cirrhosis diagnosed by clinical examination, imaging or biopsy
  • Patients with a previous history of variceal hemorrhage
  • Gastric variceal confirmed by an endoscopic examination, including IGV1 or IGV2
  • Aged 18 to 75 years
  • Adequate liver and kidney function, including Child-Turcotte-Pugh score < 12, MELD score <19, and serum creatinine less than 2 times the upper limit of normal.

Exclusion Criteria:

  • Active variceal bleeding
  • Esophageal variceal, including GOV1 or GOV2 type, mainly esophageal varices;
  • Refractory ascites
  • Patients with contraindication to treatment of TIPS, including congestive heart failure, NYHA III and IV, pulmonary arterial hypertension(>50mmHg), polycystic liver, intrahepatic duct dilatation, spontaneous bacterial peritonitis, hepatic encephalopathy
  • Patients with contraindication to treatment of Carvedilol, including asthma, insulin-dependent diabetes, peripheral vascular diseases
  • Child-Turcotte-Pugh score >=12, or MELD score >=19
  • Budd-Chiari syndrome
  • The main portal vein thrombosis is greater than 50%
  • Malignancies
  • An uncontrolled infection
  • Previously treated with TIPS, splenectomy pericardia vascular disconnection, or surgical shunts
  • HIV or HIV related illness
  • Allergic to contrast agent
  • Lactating or pregnant
  • Non-compliant patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: interventional devascularization
Interventional devascularization includes BRTO and similar procedure. Several variations of the technique exist, such as balloon-occluded antegrade transvenous obliteration or occlusion of the collateral by the placement of a vascular plug or coils.
Interventional devascularization (BRTO and its variations) is a procedure for treatment of fundal varices associated with a large gastro-/splenorenal collateral.
EXPERIMENTAL: Transjugular intrahepatic portosystemic shunt
TIPS is an artificial channel within the liver that establishes communication between the inflow portal vein and the outflow hepatic vein.
TIPS is very effective in the treatment of bleeding GV, with more than a 90% success rate for initial hemostasis. It frequently requires additional embolization of spontaneous collaterals feeding the varices. The incidence of encephalopathy was higher after TIPS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative incidence of gastric variceal rebleeding
Time Frame: 12 months
Confirmed by endoscopy
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative incidence of variceal hemorrhage related death
Time Frame: 12 months
12 months
Cumulative incidence of hepatic encephalopathy (HE)
Time Frame: 12 months
HE is classified as covert HE and overt HE
12 months
Cumulative incidence of death
Time Frame: 12 months
all cause mortality
12 months
Cumulative incidence of adverse events
Time Frame: 12 months
number of adverse events and adverse reactions in each arm
12 months
Correlation between hepatic venous pressure gradient response and cardiac index response to Carvedilol
Time Frame: 12 months
Investigate non-invasive tools for risk stratification
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Jun Tie, M.D.,Ph.D., Air Force Military Medical University, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

June 1, 2020

Primary Completion (ANTICIPATED)

December 31, 2022

Study Completion (ANTICIPATED)

December 31, 2022

Study Registration Dates

First Submitted

December 9, 2019

First Submitted That Met QC Criteria

December 11, 2019

First Posted (ACTUAL)

December 13, 2019

Study Record Updates

Last Update Posted (ACTUAL)

February 5, 2020

Last Update Submitted That Met QC Criteria

February 2, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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