Optimal encephalitis/meningitis roadmap via precise diagnosis and treatment (IMPROVE): a study protocol for a randomized controlled trial

Yi Zhang; Haocheng Zhang; Bo Deng; Ke Lin; Lei Jin; Xiaoni Liu; Yanlin Zhang; Xiaohua Chen; Yanliang Zhang; Shengjia Lu; Heqing Huang; Qiujing Wang; Tingting Feng; Weifeng Zhao; Qun Xue; Renfang Chen; Jingbo Zhang; Xiaoyan Qian; Lanlan Chen; Jingwen Ai; Xiangjun Chen; Wenhong Zhang

doi:10.1186/s12879-021-06943-6

Optimal encephalitis/meningitis roadmap via precise diagnosis and treatment (IMPROVE): a study protocol for a randomized controlled trial

BMC Infect Dis. 2022 Jan 8;22(1):40. doi: 10.1186/s12879-021-06943-6.

Authors

Yi Zhang^#¹, Haocheng Zhang^#¹, Bo Deng^#², Ke Lin^#¹, Lei Jin², Xiaoni Liu², Yanlin Zhang³, Xiaohua Chen⁴, Yanliang Zhang⁵, Shengjia Lu⁶, Heqing Huang⁷, Qiujing Wang⁸, Tingting Feng⁹, Weifeng Zhao⁹, Qun Xue¹⁰, Renfang Chen¹¹, Jingbo Zhang¹², Xiaoyan Qian¹³, Lanlan Chen¹⁴, Jingwen Ai¹⁵, Xiangjun Chen¹⁶, Wenhong Zhang¹⁷

Affiliations

¹ Department of Infectious Diseases, National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, 200040, China.
² Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
³ Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
⁴ Department of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai, China.
⁵ Department of Infectious Diseases, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
⁶ Department of Neurology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, China.
⁷ Department of Infectious Diseases, Zhuji People's Hospital of Zhejiang Province, Shaoxing, Zhejiang Province, China.
⁸ Department of Infectious Diseases, Zhoushan Hospital of Zhejiang Province, Zhoushan, Zhejiang Province, China.
⁹ Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
¹⁰ Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
¹¹ Department of Infectious Diseases, Wuxi No.5 People 's Hospital, Wuxi, Jiangsu Province, China.
¹² Department of Neurology, Blue Cross Brain Hospital, Shanghai, China.
¹³ Department of Neurology, The first people's hospital of Kunshan, Suzhou, Jiangsu Province, China.
¹⁴ Department of Neurology, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu Province, China.
¹⁵ Department of Infectious Diseases, National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, 200040, China. jingwenai1990@126.com.
¹⁶ Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China. xiangjchen@fudan.edu.cn.
¹⁷ Department of Infectious Diseases, National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, 200040, China. wenhongzhang_hs@126.com.

^# Contributed equally.

Abstract

Background: Encephalitis/meningitis brings a heavy disease burden, and the origin of disease remains unknown in 30-40% of patients. It is greatly significant that combinations of nucleic acid amplification and autoimmune antibody testing improves the diagnosis and treatment of encephalitis/meningitis. Moreover, though several diagnostic methods are in clinical use, a recognized and unified diagnosis and treatment process for encephalitis management remains unclear.

Methods: IMPROVE is a multicenter, open label, randomized controlled clinical trial that aims to evaluate the diagnostic performance, applications, and impact on patient outcomes of a new diagnostic algorithm that combines metagenomic next-generation sequencing (mNGS), multiplex polymerase chain reaction (PCR) and autoimmune antibody testing. The enrolled patients will be grouped into two parallel groups, multiplex PCR test plus autoimmune antibody group (Group I) or the mNGS plus autoimmune antibody group (Group II) with a patient ratio of 1:1. Both groups will be followed up for 12 months. The primary outcomes include the initial time of targeted treatment and the modified Rankin scale score on the 30th day of the trial. The secondary outcomes are the cerebrospinal fluid index remission rate on the 14th day, mortality rate on the 30th day, and an evaluation of diagnostic efficacy. The two groups are predicted to comprise of 484 people in total.

Discussion: To optimize the roadmap of encephalitis/meningitis, precise diagnosis, and treatment are of great significance. The effect of rapid diagnosis undoubtedly depends on the progression of new diagnostic tests, such as the new multiplex PCR, mNGS, and examination of broad-spectrum autoimmune encephalitis antibodies. This randomized-controlled study could allow us to obtain an accurate atlas of the precise diagnostic ability of these tests and their effect on the treatment and prognosis of patients. Trial registration ClinicalTrial.gov, NCT04946682. Registered 29 June 2021, 'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT04946682?term=NCT04946682&draw=2&rank=1.

Keywords: Diagnosis; Encephalitis; Meningitis; Multicenter; Randomized trial; Treatment.

Publication types

Clinical Trial Protocol

MeSH terms

Encephalitis* / diagnosis
Encephalitis* / drug therapy
Humans
Meningitis*
Metagenome
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Treatment Outcome

Associated data

ClinicalTrials.gov/NCT04946682

Abstract

Publication types

MeSH terms

Associated data

Grants and funding