The German trial on Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE): a multicenter, randomized, double-blind, placebo-controlled trial
العنوان: | The German trial on Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE): a multicenter, randomized, double-blind, placebo-controlled trial |
---|---|
المؤلفون: | M. W. Lorenz, R. von Kummer, Francisco Martinez-Torres, M-B Mackert, M. Kieser, T. Hoppe-Tichy, T. Neumann-Haefelin, Thorsten Lenhard, C. Koennecke, Uta Meyding-Lamadé, D. Claus, C. Gerloff, U. Bogdahn, Dietmar Schneider, Ralf A. Linker, B. Kieseier, W. Jakob, A. Grau, H. Steinmetz, Jürgen Bardutzky, Christina Klose, M. Klein, G. Weißheit, Christian Jacobi, E. Craemer, K. Einhäupl, V. Homberg, Kornelius Fuchs, R. Dziewas, Steffen Luntz, Anja Sander, J. Bösel, D. F. Hanley, B. Kress |
المصدر: | Neurological Research and Practice, Vol 1, Iss 1, Pp 1-9 (2019) Neurological Research and Practice |
بيانات النشر: | BMC, 2019. |
سنة النشر: | 2019 |
مصطلحات موضوعية: | 0301 basic medicine, Pediatrics, medicine.medical_specialty, Placebo-controlled study, Placebo, lcsh:RC346-429, law.invention, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Modified Rankin Scale, Clinical endpoint, Medicine, Aciclovir, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, business.industry, Glasgow Outcome Scale, Interim analysis, 030104 developmental biology, business, 030217 neurology & neurosurgery, Research Article, medicine.drug |
الوصف: | Introduction Comprehensive treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major clinical challenge. The current therapy gold standard is aciclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains around 20% and a majority of survivors suffer from severe disability. Experimental research and recent retrospective clinical observations suggest a favourable therapy response to adjuvant dexamethasone. Currently there is no randomized clinical trial evidence, however, to support the routine use of adjuvant corticosteroid treatment in HSVE. Methods The German trial of Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE) studied the effect of adjuvant dexamethasone versus placebo on top of standard aciclovir treatment in adult patients aged 18 up to 85 years with proven HSVE in German academic centers of Neurology in a randomized and double blind fashion. The trial was open from November 2007 to December 2012. The initially planned sample size was 372 patients with the option to increase to up to 450 patients after the second interim analysis. The primary endpoint was a binary functional outcome after 6 months assessed using the modified Rankin scale (mRS 0–2 vs. 3–6). Secondary endpoints included mortality after 6 and 12 months, functional outcome after 6 months measured with the Glasgow outcome scale (GOS), functional outcome after 12 months measured with mRS and GOS, quality of life as measured with the EuroQol 5D instrument after 6 and 12 months, neuropsychological testing after 6 months, cranial magnetic resonance imaging findings after 6 months, seizures up to day of discharge or at the latest at day 30, and after 6 and 12 months. Results The trial was stopped prematurely for slow recruitment after 41 patients had been randomized, 21 of them treated with dexamethasone and 20 with placebo. No difference was observed in the primary endpoint. In the full analysis set (n = 19 in each group), 12 patients in each treatment arm achieved a mRS of 0–2. Similarly, we did not observe significant differences in the secondary endpoints (GOS, mRS, quality of life, neuropsychological testing). Conclusion GACHE being prematurely terminated demonstrated challenges encountered performing randomized, placebo-controlled trials in rare life threatening neurological diseases. Based upon our trial results the use of adjuvant steroids in addition to antiviral treatment remains experimental and is at the decision of the individual treating physician. Unfortunately, the small number of study participants does not allow firm conclusions. Trial registration EudraCT-Nr. 2005–003201-81. |
اللغة: | English |
تدمد: | 2524-3489 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2365d2b9f1cf9d1150531b9a98d86801 http://link.springer.com/article/10.1186/s42466-019-0031-3 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....2365d2b9f1cf9d1150531b9a98d86801 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 25243489 |
---|