Clinical Application of High-throughput Sequencing Technology for the Diagnosis of Patients With Severe Infection

The purpose of this study is to evaluate the clinical value of high throughput sequencing of infectious pathogens for patients with severe infection, and to establish foundation for high throughput sequencing to be the clinical routine infection pathogen examination. This study is a diagnostic study, and the sample size is 320 cases. 320 participants from the department of hematology and intensive care unit who meet the inclusion criteria are randomly divided into the control group and the experimental group with 160 cases in each group. Both the participants of the control group and the experimental group undergo routine clinical diagnosis methods and treatment. In addition, the participants of the experimental group are collected the samples including whole blood, cerebrospinal fluid or alveolar lavage fluid required for high throughput sequencing of infectious pathogens during sample collection for routine pathogenic examination of infection. The pathogen diagnosis rate and the diagnostic accuracy rate between the conventional infectious pathogen tests and the high throughput sequencing of infectious pathogens will be compared in the experimental group. By gathering statistics of consultation hours and cost efficiency, the effect of high throughput sequencing of infectious pathogens on the diagnosis and treatment efficiency of the experimental group and the control group will be compared, and through these indicators, clinical application value for the diagnosis of severe infection patients by high throughput sequencing of infectious pathogens can be evaluated.

Study Overview

• Status: Withdrawn
• Conditions: Infection
• Intervention / Treatment: Diagnostic test: PMseqTM high-throughput sequencing technology

Detailed Description

The purpose of this study is to evaluate the clinical value of high throughput sequencing of infectious pathogens for patients with severe infection, and to establish foundation for high throughput sequencing to be the clinical routine infection pathogen examination.

This study is a diagnostic study, and the sample size is 320 cases. 320 participants from the department of hematology and intensive care unit who meet the inclusion criteria are randomly divided into the control group and the experimental group with 160 cases in each group. Both the participants of the control group and the experimental group undergo routine clinical diagnosis methods and treatment. In addition, the participants of the experimental group are collected the samples including whole blood, cerebrospinal fluid or alveolar lavage fluid required for high throughput sequencing of infectious pathogens during sample collection for routine pathogenic examination of infection. For the experimental group participants, the clinicians will comprehensively determine the follow-up diagnosis methods and treatment according to the clinical routine infection pathogen tests results combining with the results of high throughput sequencing of infectious pathogen, while the control group participants proceed to undergo follow-up diagnosis methods and treatment according to the results of the clinical routine infection pathogen examination. If the results of high throughput sequencing of infectious pathogens of the test group are inconsistent with the results of clinical routine infection pathogen examination, the follow-up diagnosis and treatment of the participants will be based on the results of clinical routine infection pathogen examination with priority.

For sample size assessment, we have predicted the pathogen diagnosis rate of routine clinical pathogen detection methods and high-throughput sequencing of infectious pathogens (α=0.05, β=0.10 (power=0.9)), considering that the maximum rate of missing cases was 20%, and finally got the sample content. And this study will include all subjects selected and randomized into a full analysis set under the intent-to-treat principle. After excluding participants with insufficient sample, withdrawing from the trial midway, giving up treatment and leaving the hospital, or lost to follow-up, the remaining participants will be included in the protocol set under the per-protocol principle.

As for statistical analysis, the pathogen diagnosis rate and the diagnostic accuracy rate between the conventional infectious pathogen tests and the high throughput sequencing of infectious pathogens will be compared in the experimental group. By gathering statistics of consultation hours and cost efficiency, the effect of high throughput sequencing of infectious pathogens on the diagnosis and treatment efficiency of the experimental group and the control group will be compared, and through these indicators, clinical application value for the diagnosis of severe infection patients by high throughput sequencing of infectious pathogens can be evaluated.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 14 years old, male or female
• Body temperature > 38 ℃
• Newly admitted patients
• The clinician judges that the patient may be infected, and need to undergo the infection pathogen tests
• The patients volunteer to participate in this study and sign informed consent form

Exclusion Criteria:

• Those who do not meet the inclusion criteria
• The patients who can't cooperate

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: the experimental group; high throughput sequencing of infectious pathogens	Diagnostic test: PMseqTM high-throughput sequencing technology; high throughput sequencing of infectious pathogens
No Intervention: the control group; no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathogen diagnosis rate	probability of pathogens detected	through study completion, an average of half a year
the diagnostic accuracy rate	probability of diagnosing correctly for high throughput sequencing of infectious pathogen	through study completion, an average of half a year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
money spent by participant	the money the participant spent during hospitalization	through study completion, an average of half a year
consultation hours	time of diagnosis and treatment for the participant	through study completion, an average of half a year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
the amount and type of antibiotics used	the amount and type of antibiotics used by participants in the hospital for diagnosis and treatment	through study completion, an average of half a year
28-day mortality	participants mortality within 28 days	through study completion, an average of half a year
in-hospital mortality	participants mortality during hospitalization	through study completion, an average of half a year
anti-infective treatment time	the time using for treating infection	through study completion, an average of half a year
the time with effective body temperature control	the time that body temperature of a participant is effectively and continuously controlled	through study completion, an average of half a year

Collaborators and Investigators

• Sponsor: Zhujiang Hospital
• Investigators: Principal Investigator: Lingxiao Jiang, Division of Laboratory Medicine, Zhujiang Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2021
• Primary Completion (Estimated): April 1, 2022
• Study Completion (Estimated): June 1, 2022

Study Registration Dates

• First Submitted: December 30, 2019
• First Submitted That Met QC Criteria: January 1, 2020
• First Posted (Actual): January 3, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: high throughput sequencing; severe infection; infectious pathogen
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: 20191230

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all collected IPD
• IPD Sharing Time Frame: starting 1 year after publication
• IPD Sharing Access Criteria: Related researchers
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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