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].
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.


METHODS
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.


CONCLUSIONS
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.


BACKGROUND
Current Controlled TrialsISRCTN45122933.
Martinez-Torres
Francisco
F
Department of Neurology, University of Heidelberg, Germany. Francisco.Martinez-Torres@UTSouthwestern.edu
Menon
Sanjay
S
Pritsch
Maria
M
Victor
Norbert
N
Jenetzky
Ekkehart
E
Jensen
Katrin
K
Schielke
Eva
E
Schmutzhard
Erich
E
de Gans
Jan
J
Chung
Chin-Hee
CH
Luntz
Steffen
S
Hacke
Werner
W
Meyding-Lamadé
Uta
U
D000212:Acyclovir / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003907:Dexamethasone / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D020803:Encephalitis, Herpes Simplex / Q000188:drug therapy*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D018579:Patient Selection; D012107:Research Design; D016896:Treatment Outcome; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D005938:Glucocorticoids; D003907:Dexamethasone; D000212:Acyclovir