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

NCT03990753 | Unknown DMC

• 1 other identifier: CHESS1901
• Study Type: observational
• Target: 1,000
• Locations: 3 countries
• Sites: 14

Brief 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.

Conditions

Compensated Cirrhosis

Keywords

Microbiome/Peptidome; High-risk Gastroesophageal Varices; Compensated Cirrhosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Diagnostic performance of microbiome/peptidome-based model for decompensation or death

  3 years

• Diagnostic performance of microbiome/peptidome-based model for hepatic venous pressure gradient

  1 day

Study Arms (1)

Overall eligible participants

Eligible participants will receive standard esophagogastroduodenoscopy and microbiome/peptidome examination.

Diagnostic Test: esophagogastroduodenoscopy

Interventions

esophagogastroduodenoscopy DIAGNOSTIC_TEST

standard esophagogastroduodenoscopy

Overall eligible participants

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants with compensated cirrhosis

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (14)

The Second Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

NOT YET RECRUITING

The First Hospital of Lanzhou University

Lanzhou, Gansu, China

RECRUITING

Guangdong Second Provincial General Hospital

Guangzhou, Guangdong, China

NOT YET RECRUITING

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

NOT YET RECRUITING

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, China

NOT YET RECRUITING

Xingtai People's Hospital

Xingtai, Hebei, China

NOT YET RECRUITING

Zhongda Hospital, Medical School, Southeast University

Nanjing, Jiangsu, China

NOT YET RECRUITING

The Third Hospital of Zhenjiang Affiliated Jiangsu University

Zhenjiang, Jiangsu, China

NOT YET RECRUITING

The Sixth People's Hospital of Shenyang

Shenyang, Liaoning, China

NOT YET RECRUITING

Xi'an Gaoxin Hospital

Xi’an, Shanxi, China

NOT YET RECRUITING

Tianjin Second People's Hospital

Tianjin, Tianjin Municipality, China

NOT YET RECRUITING

Zhejiang University Lishui Hospital

Lishui, Zhejiang, China

NOT YET RECRUITING

King Chulalongkorn Memorial Hospital affiliated to Chulalongkorn University

Bangkok, Thailand

NOT YET RECRUITING

Ankara University School of Medicine

Ankara, Turkey (Türkiye)

NOT YET RECRUITING

Related Publications (10)

• 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: 30215362 BACKGROUND

• 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.

  PMID: 30150716 BACKGROUND

• 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. No abstract available.

  PMID: 25398771 BACKGROUND

• 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.

  PMID: 30457484 BACKGROUND

• 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.

  PMID: 30268833 BACKGROUND

• 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.

  PMID: 25164003 BACKGROUND

• Garcia-Lezana T, Raurell I, Bravo M, Torres-Arauz M, Salcedo MT, Santiago A, Schoenenberger A, Manichanh C, Genesca 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.

  PMID: 29113028 BACKGROUND

• Hoyles L, Fernandez-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.

  PMID: 29942096 BACKGROUND

• 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: 26047908 BACKGROUND

• 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: 27786365 BACKGROUND

MeSH Terms

Interventions

Endoscopy, Digestive System

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Officials

• Hongwei Zhou, PhD

  Southern Medical University, China

  PRINCIPAL INVESTIGATOR

• Xiaolong Qi, MD

  LanZhou University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaolong Qi, MD

CONTACT

+8618588602600; qixiaolong@vip.163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 16, 2019
• First Posted: June 19, 2019
• Study Start: June 13, 2019
• Primary Completion: June 12, 2021
• Study Completion: June 12, 2022
• Last Updated: August 17, 2021

Record last verified: 2021-08

Locations

TH (1); CN (12); TU (1)