Metagenomic Next-Generation Sequencing for Diagnosis of Ascites Infection in End-stage Liver Diseases

Clinical Metagenomic Next-Generation Sequencing for Diagnosis of Ascites Infection in End-stage Liver Diseases

Ascites is the most common complication of cirrhosis, and its development is associated with substantially increased mortality. Ascites infection including spontaneous bacterial peritonitis (SBP), bacterascites and fungal infections. SBP is one of the most feared complications of ascites. The EASL guidelines recommend that diagnostic criteria of SBP is defined on the ascitic fluid polymorphonuclear leucocytes (PMN) count ≥250 cell/μl, with or without ascites fluid positive culture. However, in clinical practice. Up to 30% of hospitalized patients are considered as suspicious SBP, and treated as SBP without a laboratory-confirmed cause of infection. and is present in 10-30% of all hospitalized patients with ascites. Besides, fungal infection in ascites was aslo related to high mortality in cirrhosis patients.

Thus, to diagnose ascites infection promptly is the key step to prevent the complication. Since, the sensitivity of bacterial culture is limited even if ascites is directly injected into blood culture bottles at the besides. New method to identified the pathogen is needed.

Here, we aim to use metagenomic next-generation sequencing(mNGS) to provide the first-ever demonstration of precision medicine for the diagnosis of ascites infection in hospitalized patients, with immediate impact on clinical care and patients outcomes. The method of mNGS is undertaken by BGI Genomics Company which is a licensed clinical diagnostic laboratory in China. In this multicenter and prospective clinical study, we are planning to detect ascites sample by mNGS and compare the performance of mNGS and routine microbiological testing. Ultimately, we aim to improve the diagnosis of ascites infection and improve patients' outcomes.

Study Overview

• Status: Unknown
• Conditions: Ascites Infection
• Intervention / Treatment: Device: mNGS for pathogen detection

Detailed Description

The study is divided into 2 parts:

Firstly, the study will test 3 types of sample by means of mNGS, including ascites fluid, peritoneal dialysis fluid and postoperative drainage fluid and evaluate the sensitivity and specificity of NGS.

Secondly, the clinical validation of mNGS will be performed in multicenters for ascites infection in cirrhosis patients. Furthermore, the study will collect the paired plasma sample for NGS testing at the same time to evaluate the protential sources of microorganisms in ascites.The aim of the study is to observe the performance of mNGS in ascites infection diagosis and the protential clinical effect in cirrhsis patients.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jinjun Chen; Phone Number: 0086-18588531001; Email: chjj@smu.edu.cn
• Study Contact Backup: Name: Beiling Li; Phone Number: 0086-13570541527; Email: lbling123@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Hospitalization cirrhotic patients;
2. Age >18 years old;
3. Paitents with ascites at hospital admission.

Exclusion Criteria:

1. Pregnant women;
2. Hepatic tumor or extrahepatic related cancer;
3. Identified secondary peritonitis;
4. Ascites not related to portal hypertension;
5. Not provide written consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with ascites enrolled for mNGS testing; Patients with ascites will be enrolled in this study in order to analyze the clinical utility of mNGS for pathogen detection. There is no control group for this study (Investigators will identify historical controls by retrospective clinical documents).	Device: mNGS for pathogen detection; This assay is a metagenomic test undertaken by BGI Genomics Co., Ltd. for comprehensive detection of viruses, bacteria, fungi, and parasites in clinical samples.; Other Names: metagenomic next-generation sequencing testing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical mNGS assay performance (mNGS positive number and the pathogenics species)	mNGS positive number and the pathogenics species in ascites	within 1 month of patient enrollment in study
Classification of ascites infection based on mNGS result.	Proportion of spontaneous bacterial peritonitis, bacterascites, neutrocytic ascites and sterile ascites based on mNGS result.	within 1 month of patient enrollment in study.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of acute kindey injury.	The proportion of acute kindey injury between ascites NGS positive and negative groups.	within 1 month of patient enrollment in study.
90-day mortality		within 90 days of patient enrollment in study
The proportion of new-onset spontaneous bacterial peritonitis.		within 1 month of patient enrollment in study.

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Xiangya Hospital of Central South University; Beijing Ditan Hospital; RenJi Hospital; Southwest Hospital, China; The First Hospital of Jilin University; Shanghai Public Health Clinical Center; Wuhan Union Hospital, China; The Second Hospital of Shandong University; First Affiliated Hospital of Xinjiang Medical University; Taihe Hospital; Meng Chao Hepatobiliary Hospital of Fujian Medical University
• Investigators: Study Director: Aishan Su, Nanfang Hospital Guangzhou, Guangdong, China, 510515

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2019
• Primary Completion (Anticipated): November 30, 2020
• Study Completion (Anticipated): February 28, 2021

Study Registration Dates

• First Submitted: October 7, 2019
• First Submitted That Met QC Criteria: October 10, 2019
• First Posted (Actual): October 14, 2019

Study Record Updates

• Last Update Posted (Actual): August 14, 2020
• Last Update Submitted That Met QC Criteria: August 13, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: ascites; Ascites infection; mNGS
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Pathologic Processes; Peritoneal Diseases; Disease Attributes; Intraabdominal Infections; Liver Diseases; End Stage Liver Disease; Infections; Communicable Diseases; Ascites; Peritonitis
• Other Study ID Numbers: 010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No