Clinical trial NCT04125654: Metagenomic Next-Generation Sequencing for Diagnosis of Ascites Infection in End-stage Liver Diseases
Official title: Clinical Metagenomic Next-Generation Sequencing for Diagnosis of Ascites Infection in End-stage Liver Diseases
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Ascites Infection
Keywords: Ascites infection
ascites
mNGS
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Meng Chao Hepatobiliary Hospital of Fujian Medical University
name: The First Hospital of Jilin University
name: Beijing Ditan Hospital
name: Shanghai Public Health Clinical Center
name: Taihe Hospital
name: Xiangya Hospital of Central South University
name: Southwest Hospital, China
name: First Affiliated Hospital of Xinjiang Medical University
name: The Second Hospital of Shandong University
name: Wuhan Union Hospital, China
name: RenJi Hospital
First posted: 2019-10-14
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical mNGS assay performance (mNGS positive number and the pathogenics species)
timeFrame: within 1 month of patient enrollment in study
measure: Classification of ascites infection based on mNGS result.
timeFrame: within 1 month of patient enrollment in study.
Secondary outcomes:
measure: The proportion of acute kindey injury.
timeFrame: within 1 month of patient enrollment in study.
measure: 90-day mortality
timeFrame: within 90 days of patient enrollment in study
measure: The proportion of new-onset spontaneous bacterial peritonitis.
timeFrame: within 1 month of patient enrollment in study.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
Study officials:
affiliation: Nanfang Hospital Guangzhou, Guangdong, China, 510515
name: Aishan Su
role: STUDY_DIRECTOR
References: