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

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

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

220

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

Study Locations

  • China
    • Shaanxi
      • Xi'an, Shaanxi, China, 710032
        • Fourth Military Medical University
        • Contact:
        • Contact:

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:

  • 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

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
EXPERIMENTAL: HVPG-guided therapy
HVPG will be determined before randomization. In this arm, patients with an adequate reduction in HVPG (responders) receive carvedilol whereas nonresponders receive TIPS.
Procedure: Transjugular intrahepatic portosystemic shunt
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.
Drug: Carvedilol
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.
ACTIVE_COMPARATOR: Standard therapy
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.
Drug: Carvedilol
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.
Procedure: Endoscopic variceal ligation
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative incidence of esophageal variceal rebleeding
Time Frame: 12 months
Source of variceal rebleeding will be determined by endoscopy.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative incidence of variceal rebleeding related death
Time Frame: 12 months
12 months
Cumulative incidence of all cause mortality
Time Frame: 12 months
12 months
Cumulative incidence of patients with further decompensation
Time Frame: 12 months
Decompensation was defined as variceal rebleeding, ascites, and hepatic encephalopathy
12 months
Cumulative incidence of patients with ascites
Time Frame: 12 months
12 months
Cumulative incidence of patients with hepatic encephalopathy
Time Frame: 12 months
12 months

Collaborators and Investigators

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

Sponsor

Air Force Military Medical University, China

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, 2023

Study Completion (ANTICIPATED)

December 31, 2023

Study Registration Dates

First Submitted

February 2, 2020

First Submitted That Met QC Criteria

February 2, 2020

First Posted (ACTUAL)

February 5, 2020

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

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KY20192149-F-1

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

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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