search
Back to results

Interventional Devascularization Plus HVPG-Guided Carvedilol Therapy vs TIPS

Primary Purpose

Gastric Varices Bleeding, Liver Cirrhoses

Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
interventional devascularization
TIPS
Sponsored by
Air Force Military Medical University, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Gastric Varices Bleeding focused on measuring TIPS, HVPG, BRTO, NSBB

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    interventional devascularization

    Transjugular intrahepatic portosystemic shunt

    Arm Description

    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.

    TIPS is an artificial channel within the liver that establishes communication between the inflow portal vein and the outflow hepatic vein.

    Outcomes

    Primary Outcome Measures

    Cumulative incidence of gastric variceal rebleeding
    Confirmed by endoscopy

    Secondary Outcome Measures

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

    Full Information

    First Posted
    December 9, 2019
    Last Updated
    February 2, 2020
    Sponsor
    Air Force Military Medical University, China
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT04198259
    Brief Title
    Interventional Devascularization Plus HVPG-Guided Carvedilol Therapy vs TIPS
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    June 1, 2020 (Anticipated)
    Primary Completion Date
    December 31, 2022 (Anticipated)
    Study Completion Date
    December 31, 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Air Force Military Medical University, China

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gastric Varices Bleeding, Liver Cirrhoses
    Keywords
    TIPS, HVPG, BRTO, NSBB

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    212 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    interventional devascularization
    Arm Type
    Active Comparator
    Arm Description
    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.
    Arm Title
    Transjugular intrahepatic portosystemic shunt
    Arm Type
    Experimental
    Arm Description
    TIPS is an artificial channel within the liver that establishes communication between the inflow portal vein and the outflow hepatic vein.
    Intervention Type
    Procedure
    Intervention Name(s)
    interventional devascularization
    Intervention Description
    Interventional devascularization (BRTO and its variations) is a procedure for treatment of fundal varices associated with a large gastro-/splenorenal collateral.
    Intervention Type
    Procedure
    Intervention Name(s)
    TIPS
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Cumulative incidence of gastric variceal rebleeding
    Description
    Confirmed by endoscopy
    Time Frame
    12 months
    Secondary Outcome Measure Information:
    Title
    Cumulative incidence of variceal hemorrhage related death
    Time Frame
    12 months
    Title
    Cumulative incidence of hepatic encephalopathy (HE)
    Description
    HE is classified as covert HE and overt HE
    Time Frame
    12 months
    Title
    Cumulative incidence of death
    Description
    all cause mortality
    Time Frame
    12 months
    Title
    Cumulative incidence of adverse events
    Description
    number of adverse events and adverse reactions in each arm
    Time Frame
    12 months
    Title
    Correlation between hepatic venous pressure gradient response and cardiac index response to Carvedilol
    Description
    Investigate non-invasive tools for risk stratification
    Time Frame
    12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jun Tie, M.D.,Ph.D.
    Phone
    +862984771537
    Email
    tiejun7776@163.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Hui Chen, M.D.,Ph.D.
    Phone
    +862984771537
    Email
    qychenhui@163.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jun Tie, M.D.,Ph.D.
    Organizational Affiliation
    Air Force Military Medical University, China
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Interventional Devascularization Plus HVPG-Guided Carvedilol Therapy vs TIPS

    We'll reach out to this number within 24 hrs