Abstract Body: Introduction:
Minocycline may have effects of anti-inflammation and brain-blood barrier protection, and thus may have a potential beneficial effect on the prognosis in ischemic stroke. We aimed to investigate the efficacy and safety of Minocycline in patients with acute ischemic stroke.

Methods:
This was a multicenter, randomized, double-blind, placebo-controlled trial in 58 hospitals in China. Patients with acute ischemic stroke within 72 hours of onset and a National Institutes of Health Stroke Scale (NIHSS) score between 4 to 25 were included in the study. Patients were randomly assigned to either minocycline group or placebo group in a 1:1 ratio, receiving an initial loading dose of 200 mg and subsequent 100 mg every 12 hours for 4 days. The primary efficacy outcome was excellent functional outcome defined as modified Rankin Scale (mRS) score of 0-1 at 90 days. The main safety outcomes included symptomatic intracranial hemorrhage at 24 hours and 6 days and antibiotic-related diarrhea, constipation and enteritis at 6 days.

Results:
Between May 19, 2023, and May 20, 2024, 1724 patients (age = 63.6 ± 10.2 years, male = 67%, NIHSS score: median 5, IQR [4,7]) were randomly assigned to Minocycline treatment group (n=862) or placebo group (n=862). At 90 days, 447 patients (52.59%) in Minocycline group and 403 (47.36%) in placebo group achieved an excellent functional outcome. Minocycline treatment was significantly associated with excellent functional outcome at 90 days (RR 1.11; 95% CI, 1.03 to 1.20; P =0.006). No statistically difference of safety outcomes was found between Minocycline group and placebo group.

Conclusions:
Minocycline therapy improves functional independency in patients with acute ischemic stroke within 72 hours after onset, without an increase in symptomatic intracranial hemorrhage, or antibiotic-related diarrhea, constipation and enteritis.