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.