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

N

Nanfang Hospital, Southern Medical University

Status

Unknown

Conditions

Variceal Rebleeding
Portal Hypertension

Treatments

Procedure: Endoscopic therapy
Procedure: Laparoscopic splenectomy and pericardial devascularization
Drug: Propranolol

Study type

Interventional

Funder types

Other

Identifiers

NCT03783065
CHESS1803

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

40 participants in 2 patient groups

Experimental group
Experimental group
Description:
Procedure: Laparoscopic splenectomy and pericardial devascularization Drug: Propranolol
Treatment:
Drug: Propranolol
Procedure: Laparoscopic splenectomy and pericardial devascularization
Control group
Active Comparator group
Description:
Procedure: Endoscopic therapy Drug: Propranolol
Treatment:
Drug: Propranolol
Procedure: Endoscopic therapy

Trial contacts and locations

4

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Central trial contact

Xiaolong Qi, MD

Data sourced from clinicaltrials.gov

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