NCT03783065

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jan 2019

Longer than P75 for not_applicable

Geographic Reach
1 country

4 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 19, 2018

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 20, 2018

Completed
13 days until next milestone

Study Start

First participant enrolled

January 2, 2019

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 28, 2019

Completed
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 28, 2022

Completed
Last Updated

August 17, 2021

Status Verified

August 1, 2021

Enrollment Period

10 months

First QC Date

December 19, 2018

Last Update Submit

August 16, 2021

Conditions

Keywords

Variceal RebleedingHepatic venous pressure gradientLaparoscopic TherapyEndoscopic Therapy

Outcome Measures

Primary Outcomes (1)

  • Variceal rebleeding

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

    1 year

Secondary Outcomes (5)

  • Overall survival

    1 year

  • Hepatocellular carcinoma occurrence

    1 year

  • Venous thrombosis

    1 year

  • Quality of life score

    1 year

  • Karnofsky score

    1 year

Study Arms (2)

Experimental group

EXPERIMENTAL

Procedure: Laparoscopic splenectomy and pericardial devascularization Drug: Propranolol

Drug: PropranololProcedure: Laparoscopic splenectomy and pericardial devascularization

Control group

ACTIVE COMPARATOR

Procedure: Endoscopic therapy Drug: Propranolol

Drug: PropranololProcedure: Endoscopic therapy

Interventions

Propranolol was administrated orally while keeping monitoring heart rate and blood pressure daily.

Control groupExperimental group

Including splenectomy and pericardial devascularizaion under laparoscopy

Experimental group

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

Control group

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

The Fifth Medical Center of Chinese PLA General Hospital

Beijing, Beijing Municipality, China

NOT YET RECRUITING

The First Hospital of Lanzhou University

Lanzhou, Gansu, China

NOT YET RECRUITING

Shunde Hospital, Southern Medical University

Shunde, Guangdong, China

NOT YET RECRUITING

Xingtai People's Hospital

Xingtai, Hebei, China

RECRUITING

Related Publications (9)

  • 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.

    PMID: 30215362BACKGROUND
  • 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.

    PMID: 25177367BACKGROUND
  • 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. No abstract available.

    PMID: 20200386BACKGROUND
  • 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.

    PMID: 27786365BACKGROUND
  • 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. No abstract available.

    PMID: 26047908BACKGROUND
  • 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.

    PMID: 19724251BACKGROUND
  • 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.

    PMID: 25438286BACKGROUND
  • 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.

    PMID: 22366180BACKGROUND
  • 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.

MeSH Terms

Conditions

Hypertension, Portal

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

PhenoxypropanolaminesPropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPolycyclic Compounds

Study Officials

  • Weidong Wang, MD

    Southern Medical University, China

    PRINCIPAL INVESTIGATOR
  • Changzeng Zuo, MD

    Xingtai People's Hospital

    PRINCIPAL INVESTIGATOR
  • Xun Li, MD

    LanZhou University

    PRINCIPAL INVESTIGATOR
  • Xiaolong Qi, MD

    Nanfang Hospital, Southern Medical University

    STUDY CHAIR

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director, Hepatic Hemodynamic Lab

Study Record Dates

First Submitted

December 19, 2018

First Posted

December 20, 2018

Study Start

January 2, 2019

Primary Completion

October 28, 2019

Study Completion

October 28, 2022

Last Updated

August 17, 2021

Record last verified: 2021-08

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP, CSR
Time Frame
The data will become available upon publication of this study for 2 years.
Access Criteria
Access application is approved by principal investigators.

Locations