Microbiome/Peptidome-based Model for Non-invasive Detection of High-risk Gastroesophageal Varices in Compensated Cirrhosis (CHESS1901/APPHA1901)

Compensated Cirrhosis Clinical Trial

Official title:

Microbiome/Peptidome-based Model for Non-invasive Detection of High-risk Gastroesophageal Varices in Compensated Cirrhosis (CHESS1901/APPHA1901): A Prospective Multicenter Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03990753
• Other study ID #: CHESS1901
• Status: Recruiting
• Start date: June 13, 2019
• Est. completion date: June 12, 2022

Study information

• Verified date: August 2021
• Source: Nanfang Hospital of Southern Medical University
• Contact: Xiaolong Qi, MD
• Phone: +8618588602600
• Email: qixiaolong[@]vip.163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Variceal hemorrhage is a lethal complication in patients with cirrhosis and portal hypertension. Identification of varices needing treatment in compensated cirrhosis is, therefore, of great therapeutic and prognostic importance. The gold standard for diagnosing gastroesophageal varices and evaluating the risk of variceal hemorrhage is esophagogastroduodenoscopy. According to the Baveno VI consensus, for those with high-risk varices (HRV), either non-selective beta blockers or endoscopic band ligation is recommended for the prevention of the first variceal bleeding. However, the invasiveness and uncomfortableness during the esophagogastroduodenoscopy procedure has hindered its use in clinical practice, especially in patients with compensated cirrhosis. Sufficient accurate non-invasive tools for detection of HRV are warranted to safely avoid the use of esophagogastroduodenoscopy. Advanced technologies including next-generation sequencing and MALDI-TOF mass spectrometry have the potential to be applied in this field. The latter is a widespread adopted tool in clinical microbiology for rapid, accurate and cost-effective identification of cultured bacteria and fungi. Recently, microbiome and peptidome have been proved their roles in the end-stage liver disease (e.g. cirrhosis, hepatocellular carcinoma), which may exhibit predictive capacity of HRV. In the present study, the investigators aim to conduct a prospective, multicenter diagnostic trial in 12 sites in China, 1 site in Turkey and 1 site in Thailand to evaluate the diagnostic performance of the microbiome/peptidome-based model for HRV detection in compensated cirrhosis.

Description:

Variceal hemorrhage is a lethal complication in patients with cirrhosis and portal hypertension. Identification of varices needing treatment in compensated cirrhosis is, therefore, of great therapeutic and prognostic importance. The gold standard for diagnosing gastroesophageal varices and evaluating the risk of variceal hemorrhage is esophagogastroduodenoscopy. According to the Baveno VI consensus, for those with high-risk varices (HRV), either non-selective beta blockers or endoscopic band ligation is recommended for the prevention of the first variceal bleeding. However, the invasiveness and uncomfortableness during the esophagogastroduodenoscopy procedure has hindered its use in clinical practice, especially in patients with compensated cirrhosis. Sufficient accurate non-invasive tools for detection of HRV are warranted to safely avoid the use of esophagogastroduodenoscopy. Advanced technologies including next-generation sequencing and MALDI-TOF mass spectrometry have the potential to be applied in this field. The latter is a widespread adopted tool in clinical microbiology for rapid, accurate and cost-effective identification of cultured bacteria and fungi. Recently, microbiome and peptidome have been proved their roles in the end-stage liver disease (e.g. cirrhosis, hepatocellular carcinoma), which may exhibit predictive capacity of HRV. In the present study, the investigators aim to conduct a prospective, multicenter diagnostic trial in 12 sites (The First Hospital of Lanzhou University; Zhujiang Hospital of Southern Medical University; Nanfang Hospital of Southern Medical University; Xingtai People's Hospital; Zhongda Hospital, Medical School, Southeast University; The Third People's Hospital affiliated to Jiangsu University; Guangdong Second Provincial General Hospital; Tianjin Infectious Disease Hospital; Lishui Municipal Central Hospital; The Second Hospital of Anhui Medical University; Xi'an Gaoxin Hospital; The Sixth People's Hospital of Shenyang) in China, 1 site (Ankara University School of Medicine) in Turkey and 1 site (King Chulalongkorn Memorial Hospital affiliated to Chulalongkorn University) in Thailand to evaluate the diagnostic performance of the microbiome/peptidome-based model for HRV detection in compensated cirrhosis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: June 12, 2022
• Est. primary completion date: June 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• age 18-75 years;
• confirmed compensated cirrhosis based on liver biopsy or clinical findings;
• without decompensated events (e.g. ascites, bleeding, or overt encephalopathy);
• scheduled to undergo esophagogastroduodenoscopy;
• estimated survival time> 24 months, and model for end-stage liver disease (MELD) score< 19, and without liver transplant;
• with written informed consent.

Exclusion Criteria:

• contradictions for esophagogastroduodenoscopy;
• use of antibiotics, prebiotics, probiotics and proton pump inhibitors within 3 months upon recruitment.
• pregnancy or unknown pregnancy status.

Related Conditions & MeSH terms

• Compensated Cirrhosis
• Fibrosis
• Liver Cirrhosis

Intervention

Diagnostic Test:
• esophagogastroduodenoscopy
standard esophagogastroduodenoscopy

Locations

Country	Name	City	State
China	Guangdong Second Provincial General Hospital	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	Zhejiang University Lishui Hospital	Lishui	Zhejiang
China	Zhongda Hospital, Medical School, Southeast University	Nanjing	Jiangsu
China	The Sixth People's Hospital of Shenyang	Shenyang	Liaoning
China	Tianjin Second People's Hospital	Tianjin	Tianjin
China	Xi'an Gaoxin Hospital	Xi'an	Shanxi
China	Xingtai People's Hospital	Xingtai	Hebei
China	The Third Hospital of Zhenjiang Affiliated Jiangsu University	Zhenjiang	Jiangsu
Thailand	King Chulalongkorn Memorial Hospital affiliated to Chulalongkorn University	Bangkok
Turkey	Ankara University School of Medicine	Ankara

Sponsors (14)

Lead Sponsor

Collaborator

Nanfang Hospital of Southern Medical University

Ankara University, Guangdong Second Provincial General Hospital, King Chulalongkorn Memorial Hospital affiliated to Chulalongkorn University, LanZhou University, Southern Medical University, China, The Second Hospital of Anhui Medical University, The Sixth People's Hospital of Shenyang, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Tianjin Second People's Hospital, Xi'an Gaoxin Hospital, Xingtai People's Hospital, Zhejiang University Lishui Hospital, Zhongda Hospital, Medical School, Southeast University

Countries where clinical trial is conducted

China,  Thailand,  Turkey, 

References & Publications (10)

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

García-Lezana T, Raurell I, Bravo M, Torres-Arauz M, Salcedo MT, Santiago A, Schoenenberger A, Manichanh C, Genescà J, Martell M, Augustin S. Restoration of a healthy intestinal microbiota normalizes portal hypertension in a rat model of nonalcoholic steatohepatitis. Hepatology. 2018 Apr;67(4):1485-1498. doi: 10.1002/hep.29646. Epub 2018 Feb 19. — 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

He Y, Wu W, Zheng HM, Li P, McDonald D, Sheng HF, Chen MX, Chen ZH, Ji GY, Zheng ZD, Mujagond P, Chen XJ, Rong ZH, Chen P, Lyu LY, Wang X, Wu CB, Yu N, Xu YJ, Yin J, Raes J, Knight R, Ma WJ, Zhou HW. Regional variation limits applications of healthy gut microbiome reference ranges and disease models. Nat Med. 2018 Oct;24(10):1532-1535. doi: 10.1038/s41591-018-0164-x. Epub 2018 Aug 27. Erratum in: Nat Med. 2018 Sep 24;:. — View Citation

Hoyles L, Fernández-Real JM, Federici M, Serino M, Abbott J, Charpentier J, Heymes C, Luque JL, Anthony E, Barton RH, Chilloux J, Myridakis A, Martinez-Gili L, Moreno-Navarrete JM, Benhamed F, Azalbert V, Blasco-Baque V, Puig J, Xifra G, Ricart W, Tomlinson C, Woodbridge M, Cardellini M, Davato F, Cardolini I, Porzio O, Gentileschi P, Lopez F, Foufelle F, Butcher SA, Holmes E, Nicholson JK, Postic C, Burcelin R, Dumas ME. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nat Med. 2018 Jul;24(7):1070-1080. doi: 10.1038/s41591-018-0061-3. Epub 2018 Jun 25. Erratum in: Nat Med. 2018 Aug 9;:. — View Citation

Liu F, Ning Z, Liu Y, Liu D, Tian J, Luo H, An W, Huang Y, Zou J, Liu C, Liu C, Wang L, Liu Z, Qi R, Zuo C, Zhang Q, Wang J, Zhao D, Duan Y, Peng B, Qi X, Zhang Y, Yang Y, Hou J, Dong J, Li Z, Ding H, Zhang Y, Qi X. Development and validation of a radiomics signature for clinically significant portal hypertension in cirrhosis (CHESS1701): a prospective multicenter study. EBioMedicine. 2018 Oct;36:151-158. doi: 10.1016/j.ebiom.2018.09.023. Epub 2018 Sep 27. — View Citation

Qi X, An W, Liu F, Qi R, Wang L, Liu Y, Liu C, Xiang Y, Hui J, Liu Z, Qi X, Liu C, Peng B, Ding H, Yang Y, He X, Hou J, Tian J, Li Z. Virtual Hepatic Venous Pressure Gradient with CT Angiography (CHESS 1601): A Prospective Multicenter Study for the Noninvasive Diagnosis of Portal Hypertension. Radiology. 2019 Feb;290(2):370-377. doi: 10.1148/radiol.2018180425. Epub 2018 Nov 20. — 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

Qi X, Li Z, Huang J, Zhu Y, Liu H, Zhou F, Liu C, Xiao C, Dong J, Zhao Y, Xu M, Xing S, Xu W, Yang C. Virtual portal pressure gradient from anatomic CT angiography. Gut. 2015 Jun;64(6):1004-5. doi: 10.1136/gutjnl-2014-308543. Epub 2014 Nov 14. — View Citation

Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology. 2014 Dec;60(6):2099-108. doi: 10.1002/hep.27406. Epub 2014 Oct 29. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnostic performance of microbiome/peptidome-based model for high-risk varices	Diagnostic performance of microbiome/peptidome-based model to determine the presence or absence of high-risk varices when compared with esophagogastroduodenoscopy as the reference standard	1 day
Secondary	Diagnostic performance of microbiome/peptidome-based model for decompensation or death	Diagnostic performance of microbiome/peptidome-based model to determine the presence or absence of decompensation (defined as development of ascites, bleeding, or overt encephalopathy) or death within 3-year follow-up	3 years
Secondary	Diagnostic performance of microbiome/peptidome-based model for hepatic venous pressure gradient	Diagnostic performance of microbiome/peptidome-based model to determine the level of hepatic venous pressure gradient	1 day