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Open Access Study protocol

Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933]

Francisco Martinez-Torres19, Sanjay Menon12, Maria Pritsch3, Norbert Victor3, Ekkehart Jenetzky3, Katrin Jensen3, Eva Schielke4, Erich Schmutzhard5, Jan de Gans6, Chin-Hee Chung7, Steffen Luntz8, Werner Hacke1, Uta Meyding-Lamadé12* and the GACHE Investigators

Author Affiliations

1 Department of Neurology, University of Heidelberg, Germany

2 Department of Neurology, Krankenhaus Nordwest, Frankfurt, Germany

3 Institute for Medical Biometry and Informatics, University of Heidelberg Medical School, Germany

4 Department of Neurology, Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany

5 Department of Neurology, University of Innsbruck, Austria

6 Department of Neurology, Academic Medical Center, University of Amsterdam, The Netherlands

7 Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Germany

8 Coordination Center for Clinical Studies (KKS) Heidelberg, Germany

9 Current Address: Department of Internal Medicine, Division of Infectious Diseases University of Texas Southwestern Medical Center at Dallas, U.S.A.Department of Neurology, University of Heidelberg, Germany

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BMC Neurology 2008, 8:40  doi:10.1186/1471-2377-8-40

Published: 29 October 2008

Abstract

Background

The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question.

Design

GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage.

Conclusion

372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients.

Trial Registration

Current Controlled Trials

ISRCTN45122933