Species-specific Bacterial Detector for Fast Pathogen Diagnosis of Severe Pneumonia

Species-specific Bacterial Detector for Fast Pathogen Diagnosis of Severe Pneumonia Patients in Intensive Care Uint: a Multicentre, Randomised Controlled Trial

This study is a multicenter randomized controlled trial. The purpose of this study is to assess the efficacy of Species-specific Bacterial Dector（SSBD）for fast pathogen diagnosis and treatment in patients with severe pneumonia. Several adult ICU units from the hospitals in Jiangsu province participate the study and the hosted unit is the Department of Critical Care Medicine, Affiliated Drum Tower Hospital of Nanjing University Medical College. All patients who met the inclusion criteria are enrolled and randomly assigned either to the experiment group or to the control group, and received empiral antibiotics initially. In the experiment group, secretions from low respiratory tract are detected by SSBD and conventional culture tests simultaneously on day1,day3 and day7 after enrollment, while in the control group conventional culture tests are carried out on the same days. In the experiment group, antibiotics adjustments are made by two experienced doctors immediately when SSBD results are available, and other treatments are equivalent to those in the control group as routinely. Some clinical parameters and outcomes are recorded.

Study Overview

• Status: Not yet recruiting
• Conditions: Severe Pneumonia
• Intervention / Treatment: Diagnostic test: results of SSBD are used to guide antibiotics adjustment

Detailed Description

Sepsis is associated with high morbidity and mortality . Adequate antibiotic therapy in time could decrease mortality and reduce the length of stay in ICU for patients with sepsis or septic shock . As reported in the previous study, the mortality rate of patients increased approximately 7.6% for every hour delayed. Therefore, rapid diagnosis of pathogenic microorganisms is crucial for shortening the time of empirical antibiotic therapy and improving the prognosis of patients with sepsis.

Conventional culture test (CCT) is the most commonly used and golden standard identification method of pathogenic microorganisms in most countries. However, it showed two critical limitations: long time-consuming (2-5 days) and low sensitivity (30-50%), which limited the application of this method in the ICU . To overcome this bottleneck, several new tools were developed and showed significant improvement in time consumption and accuracy. Recently, next-generation sequencing (NGS) technology was applied to acquire the entire information of microorganisms and demonstrated great ability in diagnosing rare pathogens. However, the whole process still needs at least 2 days for the full diagnostic report with high cost. On the other hand, NGS provided too much information about microorganisms but only semi-quantification of pathogens, which was hard for most clinical doctors to extract the most important information to determine antibiotic usage. Other new emerging detection techniques designed by BioFire and Curetis are much superior in detection time than these above. However, its original principle was based on nucleotide diversity of conserved genes among species, which could not satisfy the application in the ICU due to potential false-positive results. Therefore, a unique diagnosis tool aimed at faster and more accurate pathogen identification in the ICU was still a great challenge.

Species-specific gene sequences for bacteria are found creatively. Based on these sequences, species-specific Bacterial Dector（SSBD) are designed. By SSBD, accurate and rapid detection of the most common pathogenic bacteria of sepsis could be carried out bedside conveniently in the ICU in 2~3 hours. A multiple-center randomized controlled trial will be conducted in ICU pneumonia patients to evaluate clinical benefits from SSBD.

• Study Type: Interventional
• Enrollment (Estimated): 256
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yan Wang, MD; Phone Number: 86+025-83106666-40400; Email: a_nengneng@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Nanjing First Hospital
      • Contact: Xiang Wang, MD
    • Nanjing, Jiangsu, China, 210008
      • The Affliated Drum Tower Hospital, Medical School of Nanjing University
      • Contact: Wenkui Yu, MD
    • Suqian, Jiangsu, China, 223800
      • Nanjin Drum Tower Hospital Group Suqian Hospital
      • Contact: Aihua Lin, MD
    • Suzhou, Jiangsu, China, 215500
      • Changshu No.1 People's Hospital
      • Contact: Hongwei Ye, MD
    • Taizhou, Jiangsu, China, 225300
      • Taizhou People's Hospital
      • Contact: Jilu Ye, MD
    • Wuxi, Jiangsu, China, 214200
      • Yixin People's Hospital
      • Contact: Junjie Lu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. age ≥ 18 years;
2. Pneumonia with undetermined pathogen and lower respiratory tract specimens can be obtained ;
3. signed informed consent;

Exclusion Criteria:

1. Pregnant women
2. Lactating women
3. Those who specimens of lower respiratory tract cannot be obtained;
4. The main responsibility of infection was not in the lung, but outside the lung;
5. Patients have participated in other clinical studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: the experiment group; antibiotics adjustments are made by two experienced doctors immediately when SSBD results are available, and other treatments are equivalent to those in the control group as routinely	Diagnostic test: results of SSBD are used to guide antibiotics adjustment; secretions from low resipratory will be obtained on day1,day 3 and day7 after enrollment and detected by SSBD at bedside at once. Antibiotics will be adjusted on the results by experienced doctors.
No Intervention: the control group; As routinely, antibiotics adjustmens are guided on the results of conventional culture tests and other clinical parameters by two experienced doctors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improved Acute Physiology and Chronic Health Evaluation score II score	Acute Physiology and Chronic Health Evaluation score II score will be assessed and compared on day1, day3, day7, day10 and day14	up to 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the therapeutic turnaround time (TTAT)	the time from collecting the specimen for the investigation to initiating appropriate treatment on the results available on test1, test2 ,test3 day.	on day1, day3,day7
coverage of appropriate antibiotics	numbers of patients with appropriate antibiotics	on day1, day3,day7

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of new multi-drug resistant bacteria colonization or infection	rate of multi-drug resistant bacteria colonization or infection is the index of side effects of anti-infective treatment from randomization to day 28	week 4
time of shock	time of shock from randomization to day 28	week 4

Collaborators and Investigators

• Sponsor: Chinese Medical Association
• Investigators: Study Chair: Wenkui Yu, MD, The Affliated Drum Tower Hospital, Medical School of Nanjing University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: October 13, 2021
• First Submitted That Met QC Criteria: November 20, 2021
• First Posted (Actual): December 3, 2021

Study Record Updates

• Last Update Posted (Actual): October 26, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Diagnosis, Pathogen, Pneumonia
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: 2021-260-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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