Clinical trial NCT05979350: Metagenomic NGS for Diagnosis of Pneumonia
Official title: Impact of Incorporating Metagenomic Next-generation Sequencing in the Management of Pneumonia on Diagnostic Efficiency and Outcomes: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Pneumonia
Diagnosis
Keywords: diagnosis
next-generation sequencing
outcome
pneumonia
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: National Taiwan University Hospital Hsin-Chu Branch
name: Far Eastern Memorial Hospital
First posted: 2023-08-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Paralleled 1:1 randomized trial
Primary purpose: DIAGNOSTIC

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to achieving definite diagnosis in modified intention-to-treat (mITT) analysis.
timeFrame: 7 days
Secondary outcomes:
measure: Time to achieving definite diagnosis in intention-to-treat analysis.
timeFrame: 7 days
measure: Pathogen detection rate between two groups by the 72th hour.
timeFrame: 72 hours
measure: Pathogen detection rate between two groups by the end of study.
timeFrame: 28 days
measure: Impact of mNGS on appropriate antibiotic prescription.
timeFrame: 72 hours
measure: 28-day mortality in mITT analysis.
timeFrame: 28 days
measure: 28-day mortality in ITT analysis (total cohort).
timeFrame: 28 days
measure: Impact of mNGS on respiratory and mortality outcome.
timeFrame: 28 days
measure: Impact of mNGS on the length of ICU stay
timeFrame: ICU discharge or 28 days
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Sheng-Yuan Ruan, MD
role: PRINCIPAL_INVESTIGATOR
References: