Effects of minocycline on health-related quality of life in patients with acute ischaemic stroke in China: a prespecified secondary analysis of the EMPHASIS trial.

Background: Health-related quality of life (HRQoL) is increasingly recognised as a critical outcome after acute ischaemic stroke (AIS). Minocycline may have neuroprotective potential in AIS; however, its effects on patient-reported HRQoL remain uncertain. Therefore, we aimed to evaluate the effect of minocycline on HRQoL at 90 days. Methods: This prespecified secondary analysis was based on data from the EMPHASIS trial, a parallel randomised controlled trial of minocycline in AIS at 58 centres in China from May 19, 2023, to May 20, 2024. Eligible participants were aged 18-80 years, were enrolled within 72 h of acute ischaemic stroke onset and had a National Institutes of Health Stroke Scale score of 4-25, and a pre-stroke modified Rankin Scale score of 1 or less. Participants were randomly assigned (1:1) to receive minocycline or placebo plus standard care. HRQoL was assessed using the EuroQol five-dimension three-level questionnaire (EQ-5D-3L) at 90 days. The primary outcome was EQ-5D-3L utility score; secondary outcomes were EuroQol visual analogue scale (EQ-VAS), a favourable health state defined as EQ-5D-3L utility score ≥0.75, and EQ-5D-3L domain responses. Primary analyses were conducted in the prespecified modified intention-to-treat population using linear, log-binomial, and ordinal logistic models for continuous, binary, and ordinal outcomes. Multivariable-adjusted and per-protocol sensitivity analyses were also performed. This trial was registered with ClinicalTrials.gov (NCT05836740). Findings: Of 1724 participants, 1697 were included in the final analyses. The primary analysis showed no significant between-group difference in EQ-5D-3L utility score (p = 0.224). After multivariable adjustment, the EQ-5D-3L utility score was higher in minocycline group than in placebo group (p = 0.049). The proportion of patients achieving a favourable health state was higher in the minocycline group than in the placebo group (73.4% vs 68.9%; risk ratio 1.07, 95% confidence interval 1.003-1.13; p = 0.039), with improvements in mobility (p = 0.043), self-care (p = 0.030), and usual activities (p = 0.031). EQ-VAS did not differ significantly between two groups (p = 0.420). Interpretation: Minocycline may improve health state and EQ-5D-3L domains at 90 days, supporting further evaluation as adjunctive therapy and incorporation of patient-reported outcomes into stroke trials. Funding: National Natural Science Foundation of China, The National Key Research and Development Program of China, Beijing Health Union Cardio-cerebrovascular Disease Prevention and Treatment Foundation, Noncommunicable Chronic Diseases-National Science and Technology Major Project, New Cornerstone Science Foundation, Beijing Scholar Program, Beijing Municipal Science & Technology Commission, and Capital's Funds for Health Improvement and Research.