Clinical trial NCT03783065: HVPG-guided Laparoscopic Versus Endoscopic Therapy for Variceal Rebleeding in Portal Hypertension: A Multicenter Randomized Controlled Trial (CHESS1803)
Official title: HVPG-guided Laparoscopic Versus Endoscopic Therapy for Variceal Rebleeding in Portal Hypertension: A Multicenter Randomized Controlled Trial (CHESS1803)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Portal Hypertension
Variceal Rebleeding
Keywords: Variceal Rebleeding
Hepatic venous pressure gradient
Laparoscopic Therapy
Endoscopic Therapy
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Southern Medical University, China
name: Xingtai People's Hospital
name: Beijing 302 Hospital
name: LanZhou University
First posted: 2018-12-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Variceal rebleeding
timeFrame: 1 year
Secondary outcomes:
measure: Overall survival
timeFrame: 1 year
measure: Hepatocellular carcinoma occurrence
timeFrame: 1 year
measure: Venous thrombosis
timeFrame: 1 year
measure: Quality of life score
timeFrame: 1 year
measure: Karnofsky score
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: The Fifth Medical Center of Chinese PLA General Hospital
state: Beijing
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Shunde
country: China
facility: Shunde Hospital, Southern Medical University
state: Guangdong
city: Xingtai
country: China
facility: Xingtai People's Hospital
state: Hebei
Study officials:
affiliation: Southern Medical University, China
name: Weidong Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Xingtai People's Hospital
name: Changzeng Zuo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: LanZhou University
name: Xun Li, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nanfang Hospital, Southern Medical University
name: Xiaolong Qi, MD
role: STUDY_CHAIR
References:
citation: Qi X, Berzigotti A, Cardenas A, Sarin SK. Emerging non-invasive approaches for diagnosis and monitoring of portal hypertension. Lancet Gastroenterol Hepatol. 2018 Oct;3(10):708-719. doi: 10.1016/S2468-1253(18)30232-2.
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citation: Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology. 2017 Jan;65(1):310-335. doi: 10.1002/hep.28906. Epub 2016 Dec 1. No abstract available.
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citation: Bosch J, Abraldes JG, Berzigotti A, Garcia-Pagan JC. The clinical use of HVPG measurements in chronic liver disease. Nat Rev Gastroenterol Hepatol. 2009 Oct;6(10):573-82. doi: 10.1038/nrgastro.2009.149. Epub 2009 Sep 1.
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citation: de Souza AR, La Mura V, Reverter E, Seijo S, Berzigotti A, Ashkenazi E, Garcia-Pagan JC, Abraldes JG, Bosch J. Patients whose first episode of bleeding occurs while taking a beta-blocker have high long-term risks of rebleeding and death. Clin Gastroenterol Hepatol. 2012 Jun;10(6):670-6; quiz e58. doi: 10.1016/j.cgh.2012.02.011. Epub 2012 Feb 22.
citation: Shao R, Li Z, Wang J, Qi R, Liu Q, Zhang W, Mao X, Song X, Li L, Liu Y, Zhao X, Liu C, Li X, Zuo C, Wang W, Qi X. Hepatic venous pressure gradient-guided laparoscopic splenectomy and pericardial devascularisation versus endoscopic therapy for secondary prophylaxis for variceal rebleeding in portal hypertension (CHESS1803): study protocol of a multicenter randomised controlled trial in China. BMJ Open. 2020 Jun 23;10(6):e030960. doi: 10.1136/bmjopen-2019-030960.