Next Generation Pathogen Sequencing for Prediction of Infection in Rheumatic Disease

Prediction of Infection in Patients With Rheumatic Disease at High Risk of Infection

The majority of patients diagnosed with rheumatic disease, such as systemic lupus erythematosus, inflammatory myositis, and vasculitis, will experience fever or infection during their course of therapy. The most common microbiologically documented infection is bacterial, virus, and fungal, which can be associated with the severity and mortality of disease. Current methods of diagnosis require a significant load of pathogen making early detection difficult. Delayed diagnosis and delayed optimal therapy of infection are associated with increased morbidity and mortality.

This study seeks to identify whether next generation sequencing (NGS) of pathogens can identify patients with infection treated with corticosteroid and immunosuppressive agents. This would enable preemptive targeted therapy to replace prophylaxis treatment which often leads to some adverse events and antibiotic resistance.

Study Overview

• Status: Unknown
• Conditions: Infection

Detailed Description

Plasma/Serum samples collected but not required for clinical care (discarded samples) will be collected and stored. Results of NGS will be compared between patients who develop definite infection immediately (within 72 hours) after sample collection, and those who remain well. Clinical data describing baseline information about the patient and rheumatic diseases, antibiotic and steroid or immunosuppressor therapy exposure, pathogen testing, immunology results, and infection-related events will be collected prospectively from the electronic medical record.

An initial exploratory phase will examine approximately 50 participants to determine whether the effectiveness of predicting infections. The study may then enroll up to 200 participants to collection additional data for analysis.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Zhanguo Li, M.D, Ph.D; Phone Number: +8601088324317; Email: li99@bjmu.edu.cn
• Study Contact Backup: Name: Jiali Chen, M.D; Phone Number: +8618801206400; Email: chenjiali0389@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants who are being treated at Peking University People's Hospital and who have a high risk of infection.

Description

Inclusion Criteria:

• 18 years to 70 years;
• Undergoing care for rheumatic disease at Peking University People's Hospital;
• In a category of patients who are considered by the investigator to be at high risk of infection

Exclusion Criteria:

• Any condition that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of NGS-positive results	To estimate the sensitivity of next generation pathogen sequencing for prediction of infection, the proportion of NGS-positive results in all positive infection will be given.	Once (within 72 hours of enrollment)
Proportion of NGS-negative results	To estimate the specificity of next generation pathogen sequencing for prediction of infection, the proportion of NGS-negative results in all negative infection will be given.	Once (within 72 hours of enrollment)

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Zhanguo Li, M.D, Ph.D, Peking University People's Hospital

Publications and helpful links

General Publications

• Goggin KP, Gonzalez-Pena V, Inaba Y, Allison KJ, Hong DK, Ahmed AA, Hollemon D, Natarajan S, Mahmud O, Kuenzinger W, Youssef S, Brenner A, Maron G, Choi J, Rubnitz JE, Sun Y, Tang L, Wolf J, Gawad C. Evaluation of Plasma Microbial Cell-Free DNA Sequencing to Predict Bloodstream Infection in Pediatric Patients With Relapsed or Refractory Cancer. JAMA Oncol. 2020 Apr 1;6(4):552-556. doi: 10.1001/jamaoncol.2019.4120. Erratum In: JAMA Oncol. 2020 Feb 27;:

Helpful Links

• Next Generation Pathogen Sequencing for Prediction of Adverse Events

Study record dates

Study Major Dates

• Study Start (Anticipated): January 15, 2020
• Primary Completion (Anticipated): January 15, 2021
• Study Completion (Anticipated): June 15, 2021

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 9, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 9, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Musculoskeletal Diseases; Connective Tissue Diseases; Infections; Communicable Diseases; Rheumatic Diseases; Collagen Diseases
• Other Study ID Numbers: NGPSPIRD