Effect of tNGS on CAP Patients With Initial Treatment Failure

Impact of Targeted Next-generation Sequencing on Hospitalized Patients With Community-acquired Pneumonia and Initial Treatment Failure

This is a multicenter, randomized controlled trial designed to evaluate the impact of tNGS in patients with community-acquired pneumonia who experience initial treatment failure.

Study Overview

• Status: Not yet recruiting
• Conditions: Community Acquired Pneumonia (CAP)
• Intervention / Treatment: Diagnostic test: Targeted next-generation sequencing; Diagnostic test: Conventional microbiological testing; Other: Follow-up at Day 30

Detailed Description

Community-acquired pneumonia (CAP) is a common respiratory disease and poses a major threat to global health. CAP can be caused by a wide range of respiratory pathogens, including viruses, bacteria, and fungi. However, conventional microbiological tests often fail to identify the causative pathogens, making etiological diagnosis challenging and limiting the implementation of individualized treatment strategies, which may affect patient prognosis.

Targeted next-generation sequencing (tNGS) enables the simultaneous detection of hundreds of common respiratory pathogens at a relatively low cost and has significantly improved pathogen detection rates. To further evaluate the impact of tNGS on clinical decision-making and patient outcomes in real-world practice, a multicenter randomized controlled trial is proposed by the investigators, enrolling patients with community-acquired pneumonia who experience initial treatment failure. Participants will be randomly assigned in a 1:1 ratio to either the tNGS group or the conventional testing group. Patients in the tNGS group will undergo tNGS in addition to conventional microbiological testing, whereas those in the conventional testing group will receive conventional microbiological testing alone. Length of hospital stay and other clinical effectiveness endpoints will be compared between the two groups.

• Study Type: Interventional
• Enrollment (Estimated): 524
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yeming Wang, M.D.; Phone Number: +86 84206264; Email: wwyymm_love@163.com
• Study Contact Backup: Name: Mengwei Yan; Email: yanmengwei_happy@126.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100029
      • China-Japan Friendship Hospital
      • Contact: Bin Cao; Phone Number: +86 84206264; Email: caobin_ben@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults (age ≥ 18 years)
• Diagnosed of community-acquired pneumonia
• Initial treatment failure

Exclusion Criteria:

• tNGS or mNGS already performed on respiratory samples during the current illness
• Suspected lung abscess or empyema
• Cerebral infarction within the past three months
• Dysphagia
• Nasopharyngeal carcinoma currently receiving radiotherapy
• Tracheostomy
• Long-term bedridden patients (ADL score ≤ 60)
• Pathogens identified within the past 7 days that adequately explain the current clinical presentation
• Bronchiectasis with large amounts of sputum and documented bacterial detection within the past six months
• Inability to obtain eligible respiratory samples
• CURB-65 score ≤ 1
• Expected discharge or death within 48 hours

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tNGS group; Lower respiratory tract samples collected (BALF, sputum); undergo targeted next-generation sequencing in addition to conventional microbiological testing; follow-up by telephone on day 30 (D30).	Diagnostic test: Targeted next-generation sequencing; Bronchoalveolar lavage fluid (BALF) or sputum samples will be collected within 72 hours after randomization and sent for targeted next-generation sequencing (tNGS). The test results will be reported to the attending physician within 1-2 days.; Other Names: tNGS test; Diagnostic test: Conventional microbiological testing; Bronchoalveolar lavage fluid (BALF) or sputum samples will be collected within 72 hours after randomization and sent for conventional microbiological testing. The type of conventional microbiological testing will be determined by the attending physician, and test results will be reported in approximately one week; Other: Follow-up at Day 30; A telephone visit will be conducted on or around Day 30 for study participants who are discharged or transferred to another hospital due to disease exacerbation, to collect information on survival, ICU admissions, mechanical ventilation, and medical costs.
Active Comparator: Control group; Lower respiratory tract samples collected (BALF, sputum); undergo conventional microbiological testing; follow-up by telephone on day 30 (D30).	Diagnostic test: Conventional microbiological testing; Bronchoalveolar lavage fluid (BALF) or sputum samples will be collected within 72 hours after randomization and sent for conventional microbiological testing. The type of conventional microbiological testing will be determined by the attending physician, and test results will be reported in approximately one week; Other: Follow-up at Day 30; A telephone visit will be conducted on or around Day 30 for study participants who are discharged or transferred to another hospital due to disease exacerbation, to collect information on survival, ICU admissions, mechanical ventilation, and medical costs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay	Defined as the total number of hospital days by Day 30.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day mortality	Defined as the proportion of patients who died by Day 30.	30 days
Incidence of mechanical ventilation	Defined as the proportion of patients receiving mechanical ventilation by day 30.	30 days
ICU admission rate	Defined as the incidence of transfer to the ICU within 30 days of randomization for patients initially admitted to a general ward.	30 days
Length of stay in ICU	Defined as the total number of days a patient spends in the ICU within 30 days of randomization	30 days
Duration of mechanical ventilation	Defined as the total number of days a patient receives mechanical ventilation within 30 days of randomization.	30 days
5-Day Antibiotic Modification Rate	Defined as the proportion of patients who undergo antibiotic escalation or de-escalation within 5 days after randomization.	5 days
3-Day Antibiotic Modification Rate	Defined as the proportion of patients who undergo antibiotic escalation or de-escalation within 3 days after randomization.	3 days
5-Day Other Antimicrobial Agents Modification Rate	Defined as the proportion of patients who initiate or discontinue other antimicrobial agents including antiviral, antifungal or antitubercular drugs within 5 days after randomization.	5 days
3-Day Other Antimicrobial Agents Modification Rate	Defined as the proportion of patients who initiate or discontinue other antimicrobial agents including antiviral, antifungal or antitubercular drugs within 3 days after randomization.	3 days
Cost of hospitalization	Defined as the total expenses incurred for hospitalization related to the current infection within 30 days of randomization."	30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathogen detection rate	Defined as the rate of pathogen detection for the current infection.	30 days

Collaborators and Investigators

• Sponsor: Capital Medical University
• Collaborators: China-Japan Friendship Hospital; Beijing Municipal Health Commission
• Investigators: Principal Investigator: Binghuai Lu, M.D., China-Japan Friendship Hospital; Study Chair: Bin Cao, M.D., China-Japan Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 10, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: RCT; community acquired pneumonia; targeted next generation sequencing; initial treatment failure
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Pneumonia; Community-Acquired Infections; Community-Acquired Pneumonia
• Other Study ID Numbers: 2024-1-4063

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD used in the results publication will be shared.
• IPD Sharing Supporting Information Type: ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No