HVPG-guided Laparoscopic Versus Endoscopic Therapy for Variceal Rebleeding in Portal Hypertension: A Multicenter Randomized Controlled Trial (CHESS1803)

August 16, 2021 updated by: Xiaolong Qi, Nanfang Hospital of Southern Medical University

The development of portal hypertension is a vital event in the natural progression of cirrhosis and is associated with severe complications including gastroesophageal varices bleeding. Cirrhotic patients with hemorrhagic shock and/or liver failure caused by variceal bleeding face a mortality of 5-20%.

Hepatic venous pressure gradient (HVPG) is the recommended golden standard for portal pressure assessment globally with favorable consistency and repeatability. Reducing the HVPG to levels of 12mmHg or below is associated with protection of variceal hemorrhage. An HVPG> 16mmHg indicates a higher risk of death and HVPG ≥ 20mmHg predicts failure to control bleeding, early rebleeding, and death during acute variceal hemorrhage.

The management of portal hypertension has showed a trend of diversification with the development of medication, endoscopy, radiological intervention and liver transplantation. Although medication and endoscopic therapy have achieved preferable effects and are recommended as standard of care for the prevention of variceal rebleeding, patients with HVPG≥ 16mmHg still have a high risk of treatment failure and a high rate of rebleeding. Recent years, early TIPS is recommended as the first-line therapy for the prevention of rebleeding in cirrhotic patients with HVPG≥ 20mmHg. However, for those with HVPG values between 16 to 20mmHg, there is still lack of strong evidence to demonstrate the best practice for the management.

With the rapid advancement of laparoscopic device and technique, the utility of laparoscopic splenectomy and pericardial devascularization showed less surgical trauma, bleeding and complications while retaining dependable effects compared to traditional open surgery, especially for portal hypertension with hypersplenism. In the study, the investigators aim to conduct a multicenter randomized controlled trial to compare the safety and effectiveness of HVPG-guided (16 to 20mmHg) laparoscopic versus endoscopic therapy for variceal rebleeding in patients with portal hypertension.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The development of portal hypertension is a vital event in the natural progression of cirrhosis and is associated with severe complications including gastroesophageal varices bleeding. Cirrhotic patients with hemorrhagic shock and/or liver failure caused by variceal bleeding face a mortality of 5-20%.

Hepatic venous pressure gradient (HVPG) is the recommended golden standard for portal pressure assessment globally with favorable consistency and repeatability. Reducing the HVPG to levels of 12mmHg or below is associated with protection of variceal hemorrhage. An HVPG> 16mmHg indicates a higher risk of death and HVPG ≥ 20mmHg predicts failure to control bleeding, early rebleeding, and death during acute variceal hemorrhage.

The management of portal hypertension has showed a trend of diversification with the development of medication, endoscopy, radiological intervention and liver transplantation. Although medication and endoscopic therapy have achieved preferable effects and are recommended as standard of care for the prevention of variceal rebleeding, patients with HVPG≥ 16mmHg still have a high risk of treatment failure and a high rate of rebleeding. Recent years, early TIPS is recommended as the first-line therapy for the prevention of rebleeding in cirrhotic patients with HVPG≥ 20mmHg. However, for those with HVPG values between 16 to 20mmHg, there is still lack of strong evidence to demonstrate the best practice for the management.

With the rapid advancement of laparoscopic device and technique, the utility of laparoscopic splenectomy and pericardial devascularization showed less surgical trauma, bleeding and complications while retaining dependable effects compared to traditional open surgery, especially for portal hypertension with hypersplenism. In the study, the investigators aim to conduct a multicenter (Shunde Hospital of Southern Medical University, Xingtai People's Hospital, The Fifth Medical Center of Chinese PLA General Hospital, The First Hospital of Lanzhou University) randomized controlled trial to compare the safety and effectiveness of HVPG-guided (16 to 20mmHg) laparoscopic versus endoscopic therapy for variceal rebleeding in patients with portal hypertension.

Study Type

Interventional

Enrollment (Anticipated)

40

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 Locations

  • China
    • Beijing
      • Beijing, Beijing, China
        • Not yet recruiting
        • The Fifth Medical Center of Chinese PLA General Hospital
        • Contact:
          • Zhiwei Li, MD
        • Principal Investigator:
          • Zhiwei Li, MD
    • Gansu
      • Lanzhou, Gansu, China
        • Not yet recruiting
        • The First Hospital of Lanzhou University
        • Contact:
          • Xun Li, M.D.
        • Principal Investigator:
          • Xun Li, M.D.
    • Guangdong
      • Shunde, Guangdong, China
        • Not yet recruiting
        • Shunde Hospital, Southern Medical University
        • Contact:
          • Weidong Wang, MD
        • Principal Investigator:
          • Weidong Wang, MD
    • Hebei
      • Xingtai, Hebei, China
        • Recruiting
        • Xingtai People's Hospital
        • Contact:
          • Changzeng Zuo, MD
        • Principal Investigator:
          • Changzeng Zuo, MD
        • Sub-Investigator:
          • Jitao Wang, MD

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:

  • Clinically and/or pathologically diagnosed cirrhosis with portal hypertension
  • History of varicial bleeding without receiving endoscopic treatment
  • HVPG values between 16-20 mmHg
  • ECOG score ≤ 2 or KPS score ≥ 60 during screening
  • Voluntarily participated in the study and able to provide written informed consent, understand and willing to comply with the requirements of the study
  • Child-Pugh class A or B

Exclusion Criteria:

  • Pregnant or breastfeeding women
  • Prior known or suspected malignancy (hepatocellular carcinoma, cholangiocarcinoma etc.)
  • Limited coagulation situation (Quick< 50%, PTT> 50 sec, thrombocyte count <50000 / μl or disturbed thrombocyte function)
  • Massive ascites
  • Child-Pugh class C
  • Refuse or inadequate for HVPG measurement
  • Other situations whose existence judged inadequate for participation by the investigators

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: Experimental group
Procedure: Laparoscopic splenectomy and pericardial devascularization Drug: Propranolol
Drug: Propranolol
Propranolol was administrated orally while keeping monitoring heart rate and blood pressure daily.
Procedure: Laparoscopic splenectomy and pericardial devascularization
Including splenectomy and pericardial devascularizaion under laparoscopy
ACTIVE_COMPARATOR: Control group
Procedure: Endoscopic therapy Drug: Propranolol
Drug: Propranolol
Propranolol was administrated orally while keeping monitoring heart rate and blood pressure daily.
Procedure: Endoscopic therapy
Either endoscopic variceal ligation (EVL) or cyanoacrylate injection was applied according to the condition of varices

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Variceal rebleeding
Time Frame: 1 year
The occurrence rate of gastroesophageal varices rebleeding within 1-year follow-up
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 1 year
The number of participants still alive 1 year after the therapy
1 year
Hepatocellular carcinoma occurrence
Time Frame: 1 year
The occurrence rate of hepatocellular carcinoma 1 year after the therapy
1 year
Venous thrombosis
Time Frame: 1 year
The occurrence rate of venous thrombosis upon each follow-up
1 year
Quality of life score
Time Frame: 1 year
The quality of life score measured using the 36-item Short Form Health Survey (SF-36) questionnaire upon each follow-up.
1 year
Karnofsky score
Time Frame: 1 year
The Karnofsky score categorized into low (score 10-40), intermediate (50-70), and high (80-100) upon each follow-up.
1 year

Collaborators and Investigators

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

Sponsor

Nanfang Hospital of Southern Medical University

Collaborators

LanZhou University
Beijing 302 Hospital
Xingtai People's Hospital
Southern Medical University, China

Investigators

  • Principal Investigator: Weidong Wang, MD, Southern Medical University, China
  • Principal Investigator: Changzeng Zuo, MD, Xingtai People's Hospital
  • Principal Investigator: Xun Li, MD, LanZhou University
  • Study Chair: Xiaolong Qi, MD, Nanfang Hospital of Southern Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (ACTUAL)

January 2, 2019

Primary Completion (ACTUAL)

October 28, 2019

Study Completion (ANTICIPATED)

October 28, 2022

Study Registration Dates

First Submitted

December 19, 2018

First Submitted That Met QC Criteria

December 19, 2018

First Posted (ACTUAL)

December 20, 2018

Study Record Updates

Last Update Posted (ACTUAL)

August 17, 2021

Last Update Submitted That Met QC Criteria

August 16, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHESS1803

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

IPD data including age, gender, height, weight, ethnic, past history (including time of bleeding), dignosis, co-morbidity, medication, labortory test results (including blood routine, blood ammonia, clotting time, liver function and renal function), ultrasonic results (including spleen diameter, portal vein diameter, portal vein velocity, splenic vein velocity, etc.), transient elastography results (including liver and spleen stiffness), esophagogastroduodenoscopy results, Child-pugh score, QOL and KPS scores and time of all outcome events will be shared upon publication of this study.

IPD Sharing Time Frame

The data will become available upon publication of this study for 2 years.

IPD Sharing Access Criteria

Access application is approved by principal investigators.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

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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