PneumoniaNCT05979350
Metagenomic NGS for Diagnosis of Pneumonia
A study testing Metagenomic next-generation sequencing and Standard work-up for pneumonia in people with Pneumonia and Diagnosis, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Metagenomic next-generation sequencing and Standard work-up for pneumonia
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 1 siteTaiwan
- Study dates
- 7 Aug 2023to 30 Nov 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Incorporating Metagenomic Next-generation Sequencing in the Management of Pneumonia on Diagnostic Efficiency and Outcomes: A Randomized Controlled Trial
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.
Read the 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.
- Being tested
- Metagenomic next-generation sequencing, Standard work-up for pneumonia
- Keywords
- diagnosis, next-generation sequencing, outcome, pneumonia
- Medical subject headings
- Pneumonia, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metagenomic next-generation sequencingDiagnostic 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).
Standard work-up for pneumoniaDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Diagnostic Test: Metagenomic next-generation sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 days
Secondary outcomes (8)
Time to achieving definite diagnosis in intention-to-treat analysis.
To test the robustness of mITT analysis for the primary study endpoint as compared with standard ITT analysis. (Sensitivity analysis)
Measured: 7 days
Pathogen detection rate between two groups by the 72th hour.
Proportion of participants with accurate diagnosis for the causative pathogens of pneumonia by the 72th hour after randomization in mITT analysis.
Measured: 72 hours
Pathogen detection rate between two groups by the end of study.
Proportion of participants with accurate diagnosis for the causative pathogens of pneumonia by the day 28 after randomization in mITT analysis.
Measured: 28 days
Impact of mNGS on appropriate antibiotic prescription.
Proportion of participants on effective antimicrobial therapy by the 72th hour after randomization in mITT analysis.
Measured: 72 hours
28-day mortality in mITT analysis.
Kaplan-Meier curves of 28-day survival using mITT cohort. Log-rank tests are used to test statistical significance.
Measured: 28 days
28-day mortality in ITT analysis (total cohort).
Kaplan-Meier curves of 28-day survival using total cohort. Log-rank tests are used to test statistical significance.
Measured: 28 days
Impact of mNGS on respiratory and mortality outcome.
Ventilator-free days in 28 days using the mITT cohort. Wilcoxon rank-sum test is used to test statistical significance.
Measured: 28 days
Impact of mNGS on the length of ICU stay
Curves of alive ICU discharge in 28 days after randomization using the Fine-Gray model. Death will treated as a competing risk.
Measured: ICU discharge or 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2023
- Study start7 Aug 2023
- Primary completion20 May 2025
- Study completion30 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Paralleled 1:1 randomized trial
- Masking
- None (open label)
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Taiwan University Hospital Hsin-Chu Branch, Far Eastern Memorial Hospital
- Responsible party
- Sponsor
- Investigators
- Sheng-Yuan Ruan, MD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05979350
- Sponsor's protocol ID
- 202305104RINB
- Status last verified
- Nov 2025
- First submitted
- 30 Jul 2023
- Last updated
- 19 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Incorporating Metagenomic Next-generation Sequencing in the Management of Pneumonia on Diagnostic Efficiency and Outcomes: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05979350
- Acronym / sponsor ID
- 202305104RINB
- Keywords
- diagnosis, next-generation sequencing, outcome, pneumonia
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 114 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- National Taiwan University Hospital Hsin-Chu Branch, Far Eastern Memorial Hospital
- Study start
- 7 Aug 2023 (actual)
- Primary completion
- 20 May 2025 (actual)
- Study completion
- 30 Nov 2025 (estimated)
- First posted
- 7 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Paralleled 1:1 randomized trial
| Arm | Type | Receives |
|---|---|---|
| Standard care group | Active comparator | Diagnostic Test: Standard work-up for pneumoniaEndotracheal 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. |
| mNGS group | Experimental | Diagnostic Test: Metagenomic next-generation sequencingSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metagenomic next-generation sequencingMetagenomic 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). | Diagnostic test | mNGS group |
| Standard work-up for pneumoniaEndotracheal 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 care group |
Primary outcome
Time to achieving definite diagnosis in modified intention-to-treat (mITT) analysis.
Time frame: 7 days
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.
8 secondary outcomes
Time to achieving definite diagnosis in intention-to-treat analysis.
Time frame: 7 days
Pathogen detection rate between two groups by the 72th hour.
Time frame: 72 hours
Pathogen detection rate between two groups by the end of study.
Time frame: 28 days
Impact of mNGS on appropriate antibiotic prescription.
Time frame: 72 hours
28-day mortality in mITT analysis.
Time frame: 28 days
28-day mortality in ITT analysis (total cohort).
Time frame: 28 days
Impact of mNGS on respiratory and mortality outcome.
Time frame: 28 days
Impact of mNGS on the length of ICU stay
Time frame: ICU discharge or 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sheng-Yuan Ruan, MD principal investigator
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Metagenomic next-generation sequencing and Standard work-up for pneumonia in people with Pneumonia and Diagnosis, run by National Taiwan University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to achieving definite diagnosis in modified intention-to-treat (mITT) analysis. (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2025.