Metagenomic NGS for Diagnosis of Pneumonia

National Taiwan University

Status: Active, not recruiting

Conditions: Diagnosis; Pneumonia

Treatments: Diagnostic Test: Standard work-up for pneumonia; Diagnostic Test: Metagenomic next-generation sequencing

Study type: Interventional

Funder types: Other

Identifiers

NCT05979350

202305104RINB

Details and patient eligibility

About

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.

Full description

This is an open-label, randomized, multi-center, phase 2 study that will evaluate the efficacy of incorporating mNGS in the management of severe pneumonia on accuracy and efficiency of achieving definite diagnosis of identifying causative pathogens of pneumonia, appropriate antimicrobial therapy and patient outcomes. The diagnosis of pneumonia requires radiological evidence of pneumonia and at least two of the following clinical criteria: new, or worsening cough, new or worsening expectoration of sputum, new or worsening dyspnea, hemoptysis, pleuritic chest pain, and fever (≥38.0°C). Severe pneumonia is defined as pneumonia with hypoxemia requiring orotracheal intubation and mechanical ventilation support.

Written informed consent is needed from the eligible subjects or from their legal guardian at the time of recruitment. After completing informed consent, subjects will be randomized with a 1:1 allocation ratio via a web-based randomization system to receive standard of care (SOC) using culture and serology based work-up for pathogen detection or SOC with additional mNGS method using APGseq ® (Asia Pathogenomics, New Taipei City, Taiwan) for pathogen detection. The treatment for pneumonia is suggested following the Taiwan Guidelines for the Management of Pneumonia published in 2018. After randomization, the subjects will be followed until death, discharged from the hospital or 28 days after randomization whichever comes first. The total study duration is expected to be two years from the first subject enrolled to the final analysis.

Enrollment: 114 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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114 participants in 2 patient groups

Standard care group

Active Comparator group

Description:

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.

Treatment:

Diagnostic Test: Standard work-up for pneumonia

mNGS group

Experimental group

Description:

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.

Treatment:

Diagnostic Test: Metagenomic next-generation sequencing