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

Not Applicable
Conditions
Portal Hypertension
Variceal Rebleeding
Interventions
Procedure: Laparoscopic splenectomy and pericardial devascularization
Procedure: Endoscopic therapy
Registration Number
NCT03783065
Lead Sponsor
Nanfang Hospital, Southern Medical University
Brief Summary

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.

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
40
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Experimental groupPropranololProcedure: Laparoscopic splenectomy and pericardial devascularization Drug: Propranolol
Experimental groupLaparoscopic splenectomy and pericardial devascularizationProcedure: Laparoscopic splenectomy and pericardial devascularization Drug: Propranolol
Control groupPropranololProcedure: Endoscopic therapy Drug: Propranolol
Control groupEndoscopic therapyProcedure: Endoscopic therapy Drug: Propranolol
Primary Outcome Measures
NameTimeMethod
Variceal rebleeding1 year

The occurrence rate of gastroesophageal varices rebleeding within 1-year follow-up

Secondary Outcome Measures
NameTimeMethod
Overall survival1 year

The number of participants still alive 1 year after the therapy

Hepatocellular carcinoma occurrence1 year

The occurrence rate of hepatocellular carcinoma 1 year after the therapy

Karnofsky score1 year

The Karnofsky score categorized into low (score 10-40), intermediate (50-70), and high (80-100) upon each follow-up.

Venous thrombosis1 year

The occurrence rate of venous thrombosis upon each follow-up

Quality of life score1 year

The quality of life score measured using the 36-item Short Form Health Survey (SF-36) questionnaire upon each follow-up.

Trial Locations

Locations (4)

Xingtai People's Hospital

🇨🇳

Xingtai, Hebei, China

The First Hospital of Lanzhou University

🇨🇳

Lanzhou, Gansu, China

The Fifth Medical Center of Chinese PLA General Hospital

🇨🇳

Beijing, Beijing, China

Shunde Hospital, Southern Medical University

🇨🇳

Shunde, Guangdong, China

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