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]

BMC Neurology

Volumn 8, Issue , 2008, Pages

  Martinez Torres, Francisco ^a,g   Menon, Sanjay ^a,b   Pritsch, Maria ^a   Victor, Norbert ^a   Jenetzky, Ekkehart ^a   Jensen, Katrin ^a   Schielke, Eva ^c   Schmutzhard, Erich ^d   de Gans, Jan ^e   Chung, Chin Hee ^a   Luntz, Steffen ^f   Hacke, Werner ^a   Meyding Lamadé, Uta ^a,b  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b KRANKENHAUS NORDWEST   (Germany)

^c Vivantes Auguste Viktoria Klinikum   (Germany)

^d UNIVERSITY OF INNSBRUCK   (Austria)

^e UNIVERSITY OF AMSTERDAM   (Netherlands)

^f University of Amsterdam ^*  (Germany)

^g UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACICLOVIR; DEXAMETHASONE; PLACEBO; VIRUS DNA; ANTIINFLAMMATORY AGENT; ANTIVIRUS AGENT; GLUCOCORTICOID;

ADJUVANT THERAPY; ADULT; AGED; ARTICLE; AUSTRIA; BARTHEL INDEX; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CONTROLLED CLINICAL TRIAL; DISEASE DURATION; DOUBLE BLIND PROCEDURE; GERMANY; GLASGOW OUTCOME SCALE; HERPES SIMPLEX VIRUS; HOSPITAL ADMISSION; HOSPITAL DEPARTMENT; HUMAN; INFORMED CONSENT; MAJOR CLINICAL STUDY; METHODOLOGY; MONOTHERAPY; MULTICENTER STUDY; NETHERLANDS; NEUROLOGIC DISEASE; NEUROLOGIC EXAMINATION; OUTCOME ASSESSMENT; PATIENT COMPLIANCE; PHYSICAL EXAMINATION; POLYMERASE CHAIN REACTION; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; SAMPLE SIZE; TREATMENT DURATION; VIRUS ENCEPHALITIS; ADJUVANT CHEMOTHERAPY; CONTROLLED STUDY; DRUG COMBINATION; HERPES SIMPLEX ENCEPHALITIS; MIDDLE AGED; PATIENT SELECTION; TREATMENT OUTCOME;

ACYCLOVIR; ADULT; AGED; AGED, 80 AND OVER; ANTI-INFLAMMATORY AGENTS; ANTIVIRAL AGENTS; CHEMOTHERAPY, ADJUVANT; DEXAMETHASONE; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; ENCEPHALITIS, HERPES SIMPLEX; GLUCOCORTICOIDS; HUMANS; MIDDLE AGED; PATIENT SELECTION; RESEARCH DESIGN; TREATMENT OUTCOME; YOUNG ADULT;

EID: 58149101118     PISSN: None     EISSN: 14712377     Source Type: Journal    
DOI: 10.1186/1471-2377-8-40     Document Type: Article

References (24)

1. Raschilas F Wolff M Delatour F Outcome of and prognostic factors for herpes simplex virus encephalitis in adults: Results of a multicenter study Clin Infect Dis 2002, 35:254-260. 10.1086/341405 12115090
2. McGrath N Anderson NE Croxon NC Powell KF Herpes simplex encephalitis treated with acyclovir: Diagnosis and long term outcome J Neurol Neurosurg Psychiatry 1997, 63(3):321-6. 2169720 9328248 10.1136/ jnnp.63.3.321
3. Skoldenberg B Aurelius E Hjalmarsson A Sabri F Forsgren M Andersson B Linde A Strannegard O Studahl M Hagberg L Rosengren L Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults J Neurol 2006, 253:163-170. 10.1007/s00415-005-0941-6 16222428
4. Meyding-Lamade U Seyfer S Haas J Dvorak F Kehm R Lamade W Hacke W Wildemann B Experimental herpes simplex virus encephalitis: Inhibition of the expression of inducible nitric oxide synthase in mouse brain tissue Neuroscience Letters 2002, 318:21-24. 10.1016/ S0304-3940(01)02469-7 11786216
5. Martinez-Torres FJ Wagner S Haas J Kehm R Sellner J Hacke W Meyding-Lamade U Increased presence of matrix metalloproteinases 2 and 9 in short- and long-term experimental herpes simplex virus encephalitis Neuroscience Letters 2004, 368:274-278. 10.1016/j.neulet.2004.06.064 15364410
6. Sellner J Dvorak F Zhou Y Haas J Kehm R Wildemann B Meyding-Lamade U Acute and long-term alteration of chemokine mRNA expression after anti-viral and anti-inflammatory treatment in herpes simplex virus encephalitis Neuroscience Letters 2005, 374:197-202. 10.1016/ j.neulet.2004.10.054 15663962
7. Meyding-Lamadé U Lamadé W Hess K Degen O Sartor K Oberlinner CH Hacke W Herpes simplex virus encephalitis: Chronic progressive cerebral MRI changes in patients despite good clinical recovery Clin Infect Dis 1999, 28:148-149. 10028092
8. Meyding-Lamadé U Lamadé W Kehm R Heß T Fäth A Wildemann B Haas J Hacke W Herpes simplex virus encephalitis: Chronic progressive cerebral MRI changes despite good clinical recovery and low viral load - an experimental mouse study Europ J Neurol 1999, 6:531-538. 10.1046/j.1468-1331.1999.650531.x
9. Wildemann B Ehrhart K Storch-Hagenlocher B Meyding-Lamadé U Steinvorth S Hacke W Haas J Quantitation of Herpes Simplex Virus Type 1 DNA in cells of cerebrospinal fluid of patients with herpes simplex virus encephalitis Neurology 1997, 48(5):1341-1346. 9153470
10. Thompson KA Blessing WW Wesselingh SL Herpes simplex replication and dissemination is not increased by corticosteroid treatment in a rat model of focal Herpes encephalitis J Neurovirol 2000, 6:25-32. 10.3109/ 13550280009006379 10786994
11. Meyding-Lamadé U Oberlinner C Rau P Seyfer S Heiland S Sellner J Wildemann B Lamadé W Experimental herpes simplex virus encephalitis: A combination therapy of acyclovir and glucocorticoids reduces long-term magnetic resonance imaging abnormalities J Neurovirol 2003, 9:118-125. 10.1080/713831335 12587075
12. Baringer JR Klassen T Grumm F Experimental herpes simplex virus encephalitis. Effect of corticosteroids and pyrimidine nucleoside Arch Neurol 1976, 33:442-446. 180935
13. Habel AH Brown JK Dexamethasone in herpes-simplex encephalitis Lancet 1972, 1:695. 10.1016/S0140-6736(72)90505-3 4125204
14. Upton AR Foster JB Barwick DD Dexamethasone treatment in herpes-simplex encephalitis Lancet 1971, 1:861. 10.1016/S0140-6736(71)91534-0 4102550
15. Kamei S Sekizawa T Shiota H Mizutani T Itoyama Y Takasu T Morishima T Hirayanagi K Evaluation of combination therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis J Neurol Neurosurg Psychiatry 2005, 76:1544-1549. 10.1136/ jnnp.2004.049676 16227548 1739396
16. DeGans J Beek Van de D European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators Dexamethasone in adults with bacterial meningitis N Engl J Med 2002, 20:1549-1557. 10.1056/NEJMoa021334
17. Wilhelmus KR Gee L Hauck WW Kurinij N Dawson CR Jones DB Barron BA Kaufman HE Sugar J Hyndiuk RA et al. Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis Ophthalmology 1994, 101:1883-1896. 7997324
18. Annane D Bellissant E Bollaert PE Briegel J Keh D Kupfer Y Corticosteroids for severe sepsis and septic shock: A systematic review and meta-analysis BMJ 2004, 329:480. 515196 15289273 10.1136/ bmj.38181.482222.55
19. O'Brien PC Fleming TR A multiple testing procedure for clinical trials Biometrics 1979, 35:549-556. 10.2307/2530245 497341
20. Müller HH Schäfer H Adaptive group sequential designs for clinical trials: Combining the advantages of adaptive and of classical group sequential approaches Biometrics 2001, 57:886-891. 10.1111/ j.0006-341X.2001.00886.x 11550941
21. Jennison C Turnbull BW "Group sequential methods with applications to clinical trials" Chapman & Hall, Boca Raton, London, New York, Washington, D.C 2000
22. Müller HH Schäfer H A general statistical principle for changing a design any time during the course of a trial Statistics in Medicine 2004, 23:2497-2508. 10.1002/sim.1852 15287080
23. Casagrande JT Pike MC Smith PG An improved approximative formula for calculating sample sizes for comparing two binomial distributions Biometrics 1978, 34:483-486. 10.2307/2530613 719125
24. Maurer W Hothorn LA Lehmacher W Multiple comparisons in drug clinical trials and preclinical assays: A-priori ordered hypotheses Biometrie in der chemisch-pharmazeutischen Industrie, J. Vollmar (Hrsg.), Fischer, Stuttgart 1995, 6:3-18