Efficacy and safety of minocycline on patients with acute anterior circulation ischaemic stroke undergoing mechanical thrombectomy (MIST-A) a multicentre, prospective, randomised, open-label, blinded-endpoint, phase 2 trial

Background: Minocycline has anti-inflammatory and neuroprotective properties. Prior clinical trials have shown potential benefits in acute ischaemic stroke (AIS), but its efficacy in patients who achieve successful reperfusion with mechanical thrombectomy (MT) remains unknown. 

Methods: This multicentre, prospective, randomised, open-label, blinded-endpoint, phase 2 trial was conducted at eight hospitals in China. Patients with ischaemic stroke due to anterior circulation large-vessel occlusion who achieved successful recanalisation after MT were randomly assigned (1:1) via a centralised web-based system to receive either oral minocycline (100 mg twice daily for 5 days) as an adjunct to standard care or standard care alone. The primary outcome was the infarct growth ratio (day 5 infarct volume divided by baseline infarct volume), analysed in the modified intention-to-treat population (mITT). This trial was registered at ClinicalTrials.gov, NCT05487417. 

Findings: Between Nov 21, 2022, and June 9, 2025, 189 patients were randomly assigned. After excluding two patients due to major protocol violations, 187 patients were included in the mITT analysis (94 minocycline, 93 control). The median day 5 infarct growth ratio was 1.8 (IQR 1.3–3.3) in the minocycline group and 1.6 (IQR 1.2–2.8) in the control group, yielding an adjusted geometric mean ratio of 1.10 (95% CI 0.84–1.45; p = 0.49). At day 90, 68.1% (64/94) in the minocycline group versus 72.0% (67/93) in the control group achieved functional independence (modified Rankin Scale score 0–2; adjusted risk ratio 1.00, 95% CI 0.70–1.43). There were no significant differences between the minocycline group and control group in the incidence of adverse events (76.6% [72/94] vs 68.8% [64/93]) or serious adverse events (25.5% [24/94] vs 25.8% [24/93]). 

Interpretation: In patients with AIS successfully treated with MT, adjuvant minocycline did not reduce infarct growth. The safety profile of minocycline was similar to that of standard care. These findings do not support the use of minocycline as a neuroprotective therapy in this specific population of patients.