Metagenomic NGS for Diagnosis of Pneumonia

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.

Inclusion criteria

• 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

Exclusion criteria

• 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