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

Portal Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03783065
• Other study ID #: CHESS1803
• Status: Recruiting
• Phase: N/A
• Start date: January 2, 2019
• Est. completion date: October 28, 2022

Study information

• Verified date: August 2021
• Source: Nanfang Hospital of Southern Medical University
• Contact: Xiaolong Qi, MD
• Phone: 86-18588602600
• Email: qixiaolong[@]vip.163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 28, 2022
• Est. primary completion date: October 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Portal
• Portal Hypertension
• Variceal Rebleeding

Intervention

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
• Endoscopic therapy
Either endoscopic variceal ligation (EVL) or cyanoacrylate injection was applied according to the condition of varices

Locations

Country	Name	City	State
China	The Fifth Medical Center of Chinese PLA General Hospital	Beijing	Beijing
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	Shunde Hospital, Southern Medical University	Shunde	Guangdong
China	Xingtai People's Hospital	Xingtai	Hebei

Sponsors (5)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University	Beijing 302 Hospital, LanZhou University, Shunde Hospital, Southern Medical University, Xingtai People's Hospital

Country where clinical trial is conducted

China, 

References & Publications (8)

Bosch J, Abraldes JG, Berzigotti A, García-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. Review. — View Citation

Cremers I, Ribeiro S. Management of variceal and nonvariceal upper gastrointestinal bleeding in patients with cirrhosis. Therap Adv Gastroenterol. 2014 Sep;7(5):206-16. doi: 10.1177/1756283X14538688. Review. — View Citation

de Franchis R; Baveno VI Faculty. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015 Sep;63(3):743-52. doi: 10.1016/j.jhep.2015.05.022. Epub 2015 Jun 3. — View Citation

de Souza AR, La Mura V, Reverter E, Seijo S, Berzigotti A, Ashkenazi E, García-Pagán JC, Abraldes JG, Bosch J. Patients whose first episode of bleeding occurs while taking a ß-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. Erratum in: Clin Gastroenterol Hepatol. 2014 Jun;12(6):1056. — View 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. Erratum in: Hepatology. 2017 Jul;66(1):304. — View Citation

Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med. 2010 Mar 4;362(9):823-32. doi: 10.1056/NEJMra0901512. Review. Erratum in: N Engl J Med. 2011 Feb 3;364(5):490. Dosage error in article text. — View 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. Review. — View Citation

Saad WE. Endovascular management of gastric varices. Clin Liver Dis. 2014 Nov;18(4):829-51. doi: 10.1016/j.cld.2014.07.005. Epub 2014 Oct 16. Review. — View Citation

Outcome

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