Does minocycline improve outcomes in acute ischemic stroke?

In this study, patients with acute stroke treated with minocycline had better outcomes than those treated with placebo. Minocycline is cheap and has minor complications, so if larger and more rigorous trials confirm the findings of this study, we might have a nice alternative or adjunct to thrombolytics . (LOE = 2b)

Lampl Y, Boaz M, Gilad R, et al. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology 2007;69(14):1404-1410.  [PMID:17909152]

Randomized controlled trial (single-blinded)

Unknown/not stated

Unconcealed

Inpatient (any location) with outpatient follow-up

The use of thrombolytics in acute stroke is controversial, expensive, and associated with major complications. In this study, 152 adult patients with acute moderate to severe ischemic stroke (NIH Stroke Score of more than 5) arriving between 6 hours and 24 hours after the onset of symptoms were assigned to receive 5 days of minocycline 200 mg daily or placebo. The allocation process was quasi-randomized and unconcealed, both of which are significant limitations that in other studies tend to favor the treatment group. Additionally, the researchers did not use intention to treat to analyze the outcomes, another design flaw that favors the treatment group. The 2 treatment groups were different on several characteristics: use of angiotensin-converting enzyme inhibitors, use of sulfonylureas, and prior peptic ulcer disease. The average time to treatment for each group was 12 hours. The baseline stroke severity and functional status scores were similar for each group. A research assistant masked to treatment assignment assessed stroke severity at various intervals up to 90 days after the stroke to track changes over time. Five patients taking minocycline and 9 taking placebo died during the follow-up period (P = NS). After 90 days, the patients receiving minocycline demonstrated improvements in functional status and stroke severity while patients receiving placebo tended to show no improvements. For example, in the minocycline group, the NIH Stroke Score decreased from 7.5 to 1.6, while the control group's score decreased from 7.6 to 6.5.