Second-generation Sequencing Guides the Treatment of Severe Pneumonia (NGS)

The Role of Second-generation Sequencing in the Treatment of Severe Pneumonia With Initial Treatment Failure

Investigators plan to conduct the participants level, 1:1 randomized trial at the Central ICU and respiratory ICU of Xiangya Hospital in Changsha, China, from January 1, 2018 to December 31, 2019. Participants with initial diagnosis of severe pneumonia will be first treated with empiric therapy, after 48-72 hours, the participants's condition will be evaluated, and participants who will have been initially cured and died should be excluded.The participants who will have failed the initial treatment will be then randomly divided into two groups: the NGS group and the conventional treatment group. Bronchoalveolar lavage fluid will be taken by bedside bronchoscopy when the participants underwent nasal high-flow oxygen therapy, non-invasive ventilation, and invasive ventilation,or venous blood will be taken for examination. Participants in the NGS group will be tested for both NGS and conventional pathogens, however, the routine group will be only routinely tested. According to the pathogen results, participants with non-severe pneumonia will be excluded, and medication should be adjusted under the joint guidance of infectious and respiratory specialists. Then investigators will compare the first outcome: 28-day mortality, and secondary outcome: ICU hospitalization time, mechanical ventilation time, Hospitalization costs, antibiotic use costs, SOFA scores, CURB-65 scores, APACHE scores, and other clinical indicators.

Study Overview

• Status: Unknown
• Conditions: Pneumonia; Metagenomic Next Generation Sequencing
• Intervention / Treatment: Diagnostic test: metagenomic next generation sequencing; Drug: Meropenem，Imipenem，Caspofene，Osstat; Diagnostic test: Conventional pathogen detection

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed with severe pneumonia between the ages of 18 and 85 years; the diagnosis of severe pneumonia is based on IDSA / ATS

Exclusion Criteria:

• < 18 years old, received antibiotic treatment within 14 days before admission, suffering from severe immunosuppression, multi-drug resistance, refractory tuberculosis, end-stage renal disease or liver disease (uremia, advanced liver cancer), pregnancy. Besides, we need to rule out patients who have been improved, died, and abandoned during the initial treatment。

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: metagenomic next generation sequencing; Adjust medication for patients with severe pneumonia based on mNGS results	Diagnostic test: metagenomic next generation sequencing; Pathogens in the NGS group will be tested by NGS，then according the NGS results, adjust antibiotics; Drug: Meropenem，Imipenem，Caspofene，Osstat; Meropenem，Imipenem，Caspofene，Osstat
OTHER: Conventional pathogen detection; Blood, bronchoalveolar lavage fluid (BALF), bronchial secretions samples will be collected and microbiologically tested prior to initial empirical antibiotic use.	Drug: Meropenem，Imipenem，Caspofene，Osstat; Meropenem，Imipenem，Caspofene，Osstat; Diagnostic test: Conventional pathogen detection; Morphological detection, microbial culture, nucleic acid amplification technology, serological pathogen antibody titer detection and specific pathogen PCR detection. Then, according to the pathogen results, adjust antibiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality	Using the Kaplan-Meier method to analyze the differences in mortality between the two groups within 28 days	28 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mechanical ventilation time	According to the secondary result, comprehensively evaluate the two detection methods for the treatment of patients with severe pneumonia	30 days

Collaborators and Investigators

• Sponsor: Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2018
• Primary Completion (ANTICIPATED): December 1, 2019
• Study Completion (ANTICIPATED): December 1, 2019

Study Registration Dates

• First Submitted: March 14, 2019
• First Submitted That Met QC Criteria: March 20, 2019
• First Posted (ACTUAL): March 21, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 21, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Anti-Infective Agents; Anti-Bacterial Agents; Imipenem; Meropenem
• Other Study ID Numbers: 81770080

Drug and device information, study documents

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