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HVPG-Guided Therapy vs Carvedilol Plus Endotherapy for the Prevention of Esophageal Variceal Rebleeding in Cirrhotic Patients

Primary Purpose

Liver Cirrhoses, Variceal Hemorrhage, Esophageal Varices

Status
Not yet recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Transjugular intrahepatic portosystemic shunt
Carvedilol
Endoscopic variceal ligation
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 Liver Cirrhoses focused on measuring Transjugular intrahepatic portosystemic shunt, Endoscopic variceal ligation, Non-selective β-blocker therapy, Hepatic venous pressure gradient

Eligibility Criteria

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

Inclusion Criteria:

  • Confirmed diagnosis of liver cirrhosis
  • History of esophageal variceal bleeding confirmed by endoscopy
  • Time interval between index bleeding and randomization > 5 days.
  • Child-Pugh score < 12,MELD score<19

Exclusion Criteria:

  • Clinical manifestation of active bleeding
  • Gastric variceal bleeding: GOV2,IGV1 or IGV2
  • Degree of main portal vein thrombosis > 50%
  • Refractory ascites
  • Contraindications of TIPS
  • Contraindications of NSBB
  • Budd-Chiari Syndrome
  • Malignancy tumor
  • Uncontrolled infections
  • History of portal-systemic shunt surgery
  • HIV
  • Pregnancy or breastfeeding woman
  • Poor incompliance

Sites / Locations

  • Fourth Military Medical University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

HVPG-guided therapy

Standard therapy

Arm Description

HVPG will be determined before randomization. In this arm, patients with an adequate reduction in HVPG (responders) receive carvedilol whereas nonresponders receive TIPS.

In this group, both responders and nonresponders will receive combination therapy of carvedilol and endoscopic variceal ligation as first-line therapy. If first-line therapy fails, TIPS will considered.

Outcomes

Primary Outcome Measures

Cumulative incidence of esophageal variceal rebleeding
Source of variceal rebleeding will be determined by endoscopy.

Secondary Outcome Measures

Cumulative incidence of variceal rebleeding related death
Cumulative incidence of all cause mortality
Cumulative incidence of patients with further decompensation
Decompensation was defined as variceal rebleeding, ascites, and hepatic encephalopathy
Cumulative incidence of patients with ascites
Cumulative incidence of patients with hepatic encephalopathy

Full Information

First Posted
February 2, 2020
Last Updated
February 2, 2020
Sponsor
Air Force Military Medical University, China
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1. Study Identification

Unique Protocol Identification Number
NCT04254822
Brief Title
HVPG-Guided Therapy vs Carvedilol Plus Endotherapy for the Prevention of Esophageal Variceal Rebleeding in Cirrhotic Patients
Official Title
Hepatic Vein Pressure Gradient(HVPG)-Guided Therapy vs Carvedilol Plus Endotherapy for the Prevention of Esophageal 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
Not yet recruiting
Study Start Date
June 1, 2020 (Anticipated)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (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
Variceal bleeding is a major complication of cirrhosis, associated with a hospital mortality rate of 10%-20%. Surviving patients are at high risk for recurrent hemorrhage. For these reasons, management should be directed at its prevention. Endoscopic variceal band ligation (EBL) in combination with non-selective β-blocker (NSBB) therapy is the recommended first line therapy. Transjugular intrahepatic portosystemic stent-shunt (TIPS) is the most effective method to prevent rebleeding, however, it is burdened with increased hepatic encephalopathy and deterioration of liver function in patients with advanced cirrhosis. So TIPS placement forms an alternative if first line therapy fails. Hepatic venous pressure gradient (HVPG) is currently the best available method to evaluate the presence and severity of portal hypertension. Patients who experience a reduction in HVPG of ≥20% or to <12mmHg in response to drug therapy are defined as 'responders'. The lowest rebleeding rates are observed in patients on secondary prophylaxis who are HVPG responders. A recent meta-analysis has demonstrated that combination therapy is only marginally more effective than drug therapy. This suggests that pharmacological therapy is the cornerstone of combination therapy. Adding EBL may not be the optimal approach to improve the outcome of HVPG nonresponders and HVPG non-responders are a special high-risk population that may benefit from a more aggressive approach, such as an early decision for TIPS. It recently was shown that TIPS placement within 72 hours after acute bleeding not only prevented recurrent bleeding but also improved survival. These raise the question of whether ligation together with NSBB should remain the first choice for elective secondary prophylaxis. Therefore, the purpose of the study is to compare whether HVPG-guided therapy is superior to standard combination therapy for the prevention of variceal bleeding in patients with decompensated cirrhosis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhoses, Variceal Hemorrhage, Esophageal Varices
Keywords
Transjugular intrahepatic portosystemic shunt, Endoscopic variceal ligation, Non-selective β-blocker therapy, Hepatic venous pressure gradient

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
HVPG-guided therapy
Arm Type
Experimental
Arm Description
HVPG will be determined before randomization. In this arm, patients with an adequate reduction in HVPG (responders) receive carvedilol whereas nonresponders receive TIPS.
Arm Title
Standard therapy
Arm Type
Active Comparator
Arm Description
In this group, both responders and nonresponders will receive combination therapy of carvedilol and endoscopic variceal ligation as first-line therapy. If first-line therapy fails, TIPS will considered.
Intervention Type
Procedure
Intervention Name(s)
Transjugular intrahepatic portosystemic shunt
Intervention Description
The TIPS procedures will be performed by experienced interventional radiologists. polytetrafluroethylene-covered stents were used with initial balloon dilatation to 8 mm, aiming for a decrease in portal-venous pressure gradient to less than 12 mm Hg.
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Intervention Description
Carvedilol will be started at least 5 days after the index bleeding, unless a contraindication was present. Carvedilol will be start with 6.25 mg once a day and after 3 days increase to 6.25 mg twice-daily (the maximal dose was 12.5 mg/day). Systolic arterial blood pressure should not decrease <90 mmHg.
Intervention Type
Procedure
Intervention Name(s)
Endoscopic variceal ligation
Intervention Description
For endoscopic variceal ligation, the first elective session will be carried out within 7 days of randomisation. Then EBL sessions were scheduled every 10-14 days until variceal eradication (disappearance of varices or being too small to be sucked in the banding device).
Primary Outcome Measure Information:
Title
Cumulative incidence of esophageal variceal rebleeding
Description
Source of variceal rebleeding will be determined by endoscopy.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Cumulative incidence of variceal rebleeding related death
Time Frame
12 months
Title
Cumulative incidence of all cause mortality
Time Frame
12 months
Title
Cumulative incidence of patients with further decompensation
Description
Decompensation was defined as variceal rebleeding, ascites, and hepatic encephalopathy
Time Frame
12 months
Title
Cumulative incidence of patients with ascites
Time Frame
12 months
Title
Cumulative incidence of patients with hepatic encephalopathy
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: Confirmed diagnosis of liver cirrhosis History of esophageal variceal bleeding confirmed by endoscopy Time interval between index bleeding and randomization > 5 days. Child-Pugh score < 12,MELD score<19 Exclusion Criteria: Clinical manifestation of active bleeding Gastric variceal bleeding: GOV2,IGV1 or IGV2 Degree of main portal vein thrombosis > 50% Refractory ascites Contraindications of TIPS Contraindications of NSBB Budd-Chiari Syndrome Malignancy tumor Uncontrolled infections History of portal-systemic shunt surgery HIV Pregnancy or breastfeeding woman Poor incompliance
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
Facility Information:
Facility Name
Fourth Military Medical University
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710032
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Tie, MD. Ph.D.
Phone
+862984771537
Email
tiejun7776@163.com
First Name & Middle Initial & Last Name & Degree
Hui Chen, MD. Ph.D.
Phone
+862984771537
Email
qychenhui@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

HVPG-Guided Therapy vs Carvedilol Plus Endotherapy for the Prevention of Esophageal Variceal Rebleeding in Cirrhotic Patients

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