Metagenomic NGS for Diagnosis of Pneumonia

NCT05979350 | Active Not Recruiting

• 1 other identifier: 202305104RINB
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

In this randomized controlled trial, we aim to evaluate the efficacy of incorporating mNGS in the management of pneumonia on efficiency and accuracy of causative pathogen identification, proportion of participants with effective antimicrobial therapy, length of hospitalization, and mortality.

Conditions

Pneumonia; Diagnosis

Keywords

diagnosis; next-generation sequencing; outcome; pneumonia

Outcome Measures

Primary Outcomes (1)

• Time to achieving definite diagnosis in modified intention-to-treat (mITT) analysis.

  Cumulative probability of achieving definite diagnosis in terms of accurately identifying causative pathogens of pneumonia, estimated by the Kaplan-Meier method in a time frame of 7 days in modified intention-to-treat (mITT) analysis.

  7 days

Secondary Outcomes (8)

• Time to achieving definite diagnosis in intention-to-treat analysis.

  7 days

• Pathogen detection rate between two groups by the 72th hour.

  72 hours

• Pathogen detection rate between two groups by the end of study.

  28 days

• Impact of mNGS on appropriate antibiotic prescription.

  72 hours

• 28-day mortality in mITT analysis.

  28 days

Study Arms (2)

Standard care group

ACTIVE COMPARATOR

Endotracheal aspirates, blood samples, urine samples, and nasopharyngeal swabs were obtained from the patients as soon as possible after ICU admission. Bacterial culture was performed, with the use of standard techniques, on blood samples and endotracheal aspirates. Urine antigen detection was performed for detection of L. pneumophila and S. pneumoniae. A PCR assay was performed on nasopharyngeal swabs for the detection of influenza A and B viruses and SARS-CoV-2 viruses. Fungal or mycobacterial detections, and whether to use multiplex PCR for pathogen detection, such as the FilmArray system, were determined at the discretion of the physicians.

Diagnostic Test: Standard work-up for pneumonia

mNGS group

EXPERIMENTAL

Subjects assigned to the mNGS group will receive etiology work-up followed the protocol used in the standard care group and additional mNGS testing for two specimen of mini-bronchoalveolar lavage and one specimen of blood samples retrieved at the same time of standard work-up.

Diagnostic Test: Metagenomic next-generation sequencing

Interventions

Metagenomic next-generation sequencing DIAGNOSTIC_TEST

Metagenomic NGS testing for pathogen identification will be done for airway and blood specimens using APGseq ® (Asia Pathogenomics, New Taipei City, Taiwan). The sample preparation for mNGS testing was as follows: 5-10 mL of whole blood were centrifuged at 1,600g for 10 min at 4°C to separate the plasma. Plasma samples were transferred to 2 mL sterile tubes for the following DNA or RNA extraction. In general, 300ul of plasma sample was used for DNA extraction. Total genomic DNA from samples were extracted using the column-based method (e.g. QIAamp DNA Microbiome Kit, Qiagen for DNA extraction; or QIAamp Viral RNA Mini Kit, Qiagen for RNA extraction, respectively), following the manufacturer's operational manual. The RNA was reverse transcribed and synthesized to double-stranded complementary DNA (ds cDNA) with SuperScript II Reverse Transcription Kit (Invitrogen).

mNGS group

Standard work-up for pneumonia DIAGNOSTIC_TEST

Endotracheal aspirates, blood samples, urine samples, and nasopharyngeal swabs were obtained from the patients as soon as possible after ICU admission. Bacterial culture was performed, with the use of standard techniques, on blood samples and endotracheal aspirates. Urine antigen detection was performed for detection of L. pneumophila and S. pneumoniae. A PCR assay was performed on nasopharyngeal swabs for the detection of influenza A and B viruses and SARS-CoV-2 viruses. Fungal or mycobacterial detections, and whether to use multiplex PCR for pathogen detection, such as the FilmArray system, were determined at the discretion of the physicians.

Standard care group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presenting to the ICU with a diagnosis of pneumonia (fulfilled with both radiographic and clinical criteria)
• Adults aged ≥18 years
• Orotracheally intubated
• ICU admission for \<24 hours
• APACHE II score \<35 on ICU admission

You may not qualify if:

• Life expectancy below 4 weeks
• With an existing directive to withhold life-sustaining treatment
• Patients not willing or able to provide a lower respiratory tract sample at ICU admission
• Previous work-up has identified specific pathogens which can account for the index event of pneumonia
• Multiplex PCR or NGS testing has been done for pathogen detection before screening

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• National Taiwan University Hospital Hsin-Chu Branch: collaborator
• Far Eastern Memorial Hospital: collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Pneumonia; Disease

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sheng-Yuan Ruan, MD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Paralleled 1:1 randomized trial

Study Record Dates

• First Submitted: July 30, 2023
• First Posted: August 7, 2023
• Study Start: August 7, 2023
• Primary Completion: May 20, 2025
• Study Completion: November 30, 2025
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)