Neurol India Home 
 

EDITORIAL
Year : 2012  |  Volume : 60  |  Issue : 1  |  Page : 1--2

Minocycline: The search for a community hospital acute stroke therapy

David C Hess1, Virginia J Howard2, George Howard3,  
1 Department of Neurology, Georgia Health Sciences University, Augusta, GA, USA
2 Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
3 Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence Address:
David C Hess
Department of Neurology, Georgia Health Sciences University, Augusta, GA 30912
USA




How to cite this article:
Hess DC, Howard VJ, Howard G. Minocycline: The search for a community hospital acute stroke therapy.Neurol India 2012;60:1-2


How to cite this URL:
Hess DC, Howard VJ, Howard G. Minocycline: The search for a community hospital acute stroke therapy. Neurol India [serial online] 2012 [cited 2020 Oct 23 ];60:1-2
Available from: https://www.neurologyindia.com/text.asp?2012/60/1/1/93580


Full Text

Stroke therapies are needed that work in stroke patients in Mumbai and Shanghai, and in rural locales such as Chengannur, India, and Sandersville, Georgia. In the US, nearly 64% of hospitals do not use tissue plasminogen activator (tPA) in patients with acute ischemic stroke [1] and its use is rare in rural areas throughout the world. As a public health measure, safe drugs for stroke are needed that can be given in a wide variety of clinical settings and in those with limited infrastructures. Minocycline, a "repurposed" drug for stroke with multiple mechanisms of action, is very safe, well tolerated, inexpensive, easy to administer, and could be used nearly anywhere and everywhere. [2]

In a randomized, single-blind, placebo-controlled trial in this issue of Neurology India, oral or nasogastric tube-administered minocycline at a dose of 200 mg/day for 5 days was safe and effective in acute ischemic stroke. Minocycline was administered at a mean time of 13.5 hours after symptom onset. Minocycline-treated patients had significantly lower National Institute of Health Stroke Scale (NIHSS) and lower mRS at 30 and 90 days, suggestive of a benefit. The trial was small (50 subjects) and the raters of the scales were not blinded, potentially introducing bias. In addition, the relatively small size of the study limited the ability of randomization to evenly balance the treatment groups, where there appear to be a number of potentially clinically significant (albeit statistically non-significant) differences. Specifically, the actively treated group was at a lower risk at baseline as it was approximately 4 years younger on average, and had a lower prevalence of hypertension, diabetes, heart disease, dyslipidemia, and alcohol intake, although there were more smokers and a higher prevalence of chronic obstructive pulmonary disease (COPD) in the control group. While these differences were not statistically significant, the number and magnitude of differences that generally benefited the active treatment group may have played a role in the better long-term outcome. However, this concern is somewhat offset by the roughly equivalent stroke severity in the two groups at baseline, with the active-treatment group having a slightly higher mean baseline NIH Stroke Scale score. [3] The evidence of a potential beneficial effect of minocycline continues to mount, as this trial was similar in design and results to an Israeli trial of oral minocycline. [4] In that randomized trial of 150 subjects, the raters of the outcomes were blinded and minocycline showed a favorable effect on 7, 30, and 90 day outcomes as measured by the NIHSS and mRS. Remarkably, minocycline was effective in both these trials when its administration was delayed to 12-13 hours after symptom onset. Together, these studies have randomized 200 subjects and suggest that minocycline is effective in acute stroke. Neither trial used minocycline in the setting of IV tPA. The latter may be seen as an advantage as tPA's use is limited in most parts of the world.

Before minocycline can be recommended for acute stroke and becomes part of clinical guidelines, more clinical trial evidence is needed. To achieve Grade A evidence, a large randomized, double-blind, placebo-controlled trial is required. [5] It is also important to determine if minocycline is effective when given in combination with tPA or alone. Pre-clinical studies and clinical trial data suggest that minocycline may reduce tPA-related Intracerebral hemorrhage (ICH), the most feared complication of IV tPA . [6],[7],[8] If minocycline is shown effective in a large trial, the stroke community would have an affordable and safe agent that can be used even in rural and community hospitals. If minocycline reduces tPA-related ICH, then it is likely that tPA use would increase and benefit more patients. Moreover, minocycline would be an ideal drug to use in a pre-hospital setting, administered by emergency personnel in the field, as there is evidence of activity against ICH, [9] making it possible in the future to start minocycline even before a CT scan. Given the high incidence of stroke throughout the world, especially in Asian countries, and the aging world population, minocycline could have a major effect on the brain health of the world.

References

1Kleindorfer D, Xu Y, Moomaw CJ, Khatri P, Adeoye O, Hornung R. US geographic distribution of rt-PA utilization by hospital for acute ischemic stroke. Stroke 2009;40:3580-4.
2Fagan SC, Cronic LE, Hess DC. Minocycline development for acute ischemic stroke. Transl Stroke Res 2011;2:202-8.
3Padma MV, Bhasin A, Bhatia R, Garg A, Gaikwad S, Prasad K, et al. Efficacy of Minocycline in Acute Ischemic Stroke: A single-blinded, placebo-controlled trial. Neurol India 2012;60:23-8.
4Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, et al. Minocycline treatment in acute stroke: An open-label, evaluator-blinded study. Neurology 2007;69:1404-10.
5Tricoci P, Allen JM, Kramer JM, Califf RM, Smith SC, Jr. Scientific evidence underlying the ACC/AHA clinical practice guidelines. JAMA 2009;301:831-41.
6Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark WM, et al. Minocycline to improve neurologic outcome in stroke (MINOS): A dose-finding study. Stroke 2010;41:2283-7.
7Machado LS, Sazonova IY, Kozak A, Wiley DC, El-Remessy AB, Ergul A, et al. Minocycline and tissue-type plasminogen activator for stroke: Assessment of interaction potential. Stroke 2009;40:3028-33.
8Murata Y, Rosell A, Scannevin RH, Rhodes KJ, Wang X, Lo EH. Extension of the thrombolytic time window with minocycline in experimental stroke. Stroke 2008;39:3372-7.
9Zhao F, Hua Y, He Y, Keep RF, Xi G. Minocycline-induced attenuation of iron overload and brain injury after experimental intracerebral hemorrhage. Stroke 2011;42:3587-93.