Evaluation of droplet digital PCR rapid detection method and precise diagnosis and treatment for suspected sepsis (PROGRESS): a study protocol for a multi-center pragmatic randomized controlled trial

Yuanhan Zhao, Ke Lin, Haocheng Zhang, Guanmin Yuan, Yanliang Zhang, Jingye Pan, Liang Hong, Yan Huang, Ying Ye, Lisu Huang, Xiaohua Chen, Jun Liu, Xiang Li, Xiaoju He, Qiaoyan Yue, Hong Zhang, Aiming Zhou, Yangyang Zhuang, Jie Chen, Caixia Wu, Wei Zhou, Fujing Cai, Shengguo Zhang, Liang Li, Shaling Li, Tingting Bian, Jiabin Li, Jun Yin, Zhengshang Ruan, Shanshan Xu, Yan Zhang, Jie Chen, Ying Zhang, Jun Han, Tingting Su, Fan Tu, Lijing Jiang, Chen Lei, Qiu Du, Jingwen Ai, Wenhong Zhang, Yuanhan Zhao, Ke Lin, Haocheng Zhang, Guanmin Yuan, Yanliang Zhang, Jingye Pan, Liang Hong, Yan Huang, Ying Ye, Lisu Huang, Xiaohua Chen, Jun Liu, Xiang Li, Xiaoju He, Qiaoyan Yue, Hong Zhang, Aiming Zhou, Yangyang Zhuang, Jie Chen, Caixia Wu, Wei Zhou, Fujing Cai, Shengguo Zhang, Liang Li, Shaling Li, Tingting Bian, Jiabin Li, Jun Yin, Zhengshang Ruan, Shanshan Xu, Yan Zhang, Jie Chen, Ying Zhang, Jun Han, Tingting Su, Fan Tu, Lijing Jiang, Chen Lei, Qiu Du, Jingwen Ai, Wenhong Zhang

Abstract

Background: Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for sepsis management. As an emerging rapid and sensitive pathogen detection tool, digital droplet PCR (ddPCR) has shown promising potential in rapid identification of pathogens and antimicrobial resistance genes. However, the diagnostic value and clinical impact of ddPCR tests remains to be studied in patients with suspected sepsis. PROGRESS trial is aimed to evaluate the clinical effectiveness of a novel ddPCR assay compared with standard practice.

Methods: PROGRESS is a multicenter, open-label, pragmatic randomized controlled trial (pRCT) set in ten hospitals, including departments of infectious disease and intensive care units. In this study, a total of 2292 patients with suspected sepsis will be randomly assigned to two arms: the ddPCR group and the control group with a ratio of 3:1. The primary outcome is the diagnostic efficacy, that is, the sensitivity and specificity of the ddPCR assay compared with the synchronous blood culture. Secondary outcomes include the mortality rates and the mean Sequential Organ Failure Assessment (SOFA) score at follow-up time points, the length of stay in the hospital, the time to directed antimicrobial therapy, duration of broad-spectrum antibiotic use, and the EQ-5D-5L score on day 90.

Discussion: It is the first multicenter pragmatic RCT to explore the diagnostic efficacy and clinical impact of the ddPCR assay in patients with suspected sepsis, taking advantage of both RCT's ability to establish causality and the feasibility of pragmatic approaches in real-world studies (RWS). This trial will help us to get a comprehensive view of the assay's capacity for precise diagnosis and treatment of sepsis. It has the potential to monitor the pathogen load change and to guide the antimicrobial therapy, making a beneficial impact on the prognosis of sepsis patients.

Trial registration: ClinicalTrial.gov, NCT05190861. Registered January 13, 2022-'Retrospectively registered', https://ichgcp.net/clinical-trials-registry/NCT05190861 .

Keywords: Multicenter; Randomized trial; Rapid diagnostics; Sepsis; Septic shock.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart of PROGRESS trial procedure

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