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

NCT ID: NCT03783065

Last Updated: 2021-08-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-02

Study Completion Date

2022-10-28

Brief Summary

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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

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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.

Conditions

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Portal Hypertension Variceal Rebleeding

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Experimental group

Procedure: Laparoscopic splenectomy and pericardial devascularization Drug: Propranolol

Group Type EXPERIMENTAL

Propranolol

Intervention Type DRUG

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

Laparoscopic splenectomy and pericardial devascularization

Intervention Type PROCEDURE

Including splenectomy and pericardial devascularizaion under laparoscopy

Control group

Procedure: Endoscopic therapy Drug: Propranolol

Group Type ACTIVE_COMPARATOR

Propranolol

Intervention Type DRUG

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

Endoscopic therapy

Intervention Type PROCEDURE

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

Interventions

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Propranolol

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

Intervention Type DRUG

Laparoscopic splenectomy and pericardial devascularization

Including splenectomy and pericardial devascularizaion under laparoscopy

Intervention Type PROCEDURE

Endoscopic therapy

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

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Southern Medical University, China

OTHER

Sponsor Role collaborator

Xingtai People's Hospital

OTHER

Sponsor Role collaborator

Beijing 302 Hospital

OTHER

Sponsor Role collaborator

LanZhou University

OTHER

Sponsor Role collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role lead

Responsible Party

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Xiaolong Qi

Director, Hepatic Hemodynamic Lab

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Weidong Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Southern Medical University, China

Changzeng Zuo, MD

Role: PRINCIPAL_INVESTIGATOR

Xingtai People's Hospital

Xun Li, MD

Role: PRINCIPAL_INVESTIGATOR

LanZhou University

Xiaolong Qi, MD

Role: STUDY_CHAIR

Nanfang Hospital, Southern Medical University

Locations

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The Fifth Medical Center of Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Site Status NOT_YET_RECRUITING

The First Hospital of Lanzhou University

Lanzhou, Gansu, China

Site Status NOT_YET_RECRUITING

Shunde Hospital, Southern Medical University

Shunde, Guangdong, China

Site Status NOT_YET_RECRUITING

Xingtai People's Hospital

Xingtai, Hebei, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Xiaolong Qi, MD

Role: CONTACT

86-18588602600

Facility Contacts

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Zhiwei Li, MD

Role: primary

Xun Li, M.D.

Role: primary

Weidong Wang, MD

Role: primary

Changzeng Zuo, MD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 30215362 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25177367 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20200386 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27786365 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26047908 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19724251 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25438286 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22366180 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32580978 (View on PubMed)

Other Identifiers

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CHESS1803

Identifier Type: -

Identifier Source: org_study_id

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