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
About this trial
This is an interventional prevention trial for Gastric Varices Bleeding focused on measuring TIPS, HVPG, BRTO, NSBB
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
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
NCT ID
NCT04198259
First Posted
December 9, 2019
Last Updated
February 2, 2020
Sponsor
Air Force Military Medical University, China
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
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Interventional Devascularization Plus HVPG-Guided Carvedilol Therapy vs TIPS
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