Initiation of the multi-target anti-neuroinflammatory drug minocycline within 72 hours of acute ischemic stroke had a significant benefit in functional outcome compared to placebo, with no increased safety risks, according to findings from the EMPHASIS trial published Jan. 30 in The Lancet.

The double-blind trial, conducted at 58 hospitals across China, randomized 1,724 patients (median age 65; 33% women) 1:1 to oral placebo or minocycline therapy, beginning with a loading dose of 200 mg followed by 100 mg every 12 hours for four days. Study patients had suffered an ischemic stroke within the previous 72 hours and had a National Institutes of Health Stroke Scale (NIHSS) score of 4-25 (median 5) and a level of consciousness score of ≤1.

Results at 90 days showed that more patients in the minocycline than the placebo group achieved excellent function (53% vs. 47%) as measured by the modified Rankin Scale score [mRS] 0-1; adjusted risk ratio 1.11; p=0.0061. Full mRS shift analysis likewise favored minocycline (adjusted common odds ratio 1.19; p=0.018).

A greater improvement in the NIHSS score was observed with minocycline (p=0.015) along with greater reduction in hs-CRP at six days (p=0.067), compared with placebo.

Study authors Yao Lu, MD, et el., noted a possible stronger effect in patients with a history of alcohol use or with large-artery disease or small vessel disease, with no differences by age or sex.

Safety was similar between the minocycline and placebo groups, with similar incidence of symptomatic intracranial hemorrhage at both 24 hours (0.1% vs. 0%) and six days (0.3% vs. 0%), serious adverse events (4.6% vs. 5.9%; p=0.24) and mortality (1.6% vs. 2.3%; hazard ratio, 0.69; p=0.28).

"These findings suggest that minocycline could be a safe, cost-effective, and accessible therapeutic option for patients with acute [ischemic] stroke," Lu, et al. write. However, they note that the trial demographics – a homogenous Asian population with an upper age limit of 80 years and a median baseline NIHSS score of 5 – limits the generalizability of the results, and "further studies are warranted to confirm these results and to establish whether the benefits extend to patients with more severe or minor strokes."