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

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