Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults.
BACKGROUND
Tuberculous meningitis kills or disables more than half of those affected with the disease. Previous studies have been too small to determine whether adjunctive treatment with corticosteroids can reduce the risk of disability or death among adults with tuberculous meningitis, and the effect of coinfection with the human immunodeficiency virus (HIV) is unclear.


METHODS
We performed a randomized, double-blind, placebo-controlled trial in Vietnam in patients over 14 years of age who had tuberculous meningitis, with or without HIV infection, to determine whether adjunctive treatment with dexamethasone reduced the risk of death or severe disability after nine months of follow-up. We conducted prespecified subgroup analyses and intention-to-treat analyses.


RESULTS
A total of 545 patients were randomly assigned to groups that received either dexamethasone (274 patients) or placebo (271 patients). Only 10 patients (1.8 percent) had been lost to follow-up at nine months of treatment. Treatment with dexamethasone was associated with a reduced risk of death (relative risk, 0.69; 95 percent confidence interval, 0.52 to 0.92; P=0.01). It was not associated with a significant reduction in the proportion of severely disabled patients (34 of 187 patients [18.2 percent] among survivors in the dexamethasone group vs. 22 of 159 patients [13.8 percent] in the placebo group, P=0.27) or in the proportion of patients who had either died or were severely disabled after nine months (odds ratio, 0.81; 95 percent confidence interval, 0.58 to 1.13; P=0.22). The treatment effect was consistent across subgroups that were defined by disease-severity grade (stratified relative risk of death, 0.68; 95 percent confidence interval, 0.52 to 0.91; P=0.007) and by HIV status (stratified relative risk of death, 0.78; 95 percent confidence interval, 0.59 to 1.04; P=0.08). Significantly fewer serious adverse events occurred in the dexamethasone group than in the placebo group (26 of 274 patients vs. 45 of 271 patients, P=0.02).


CONCLUSIONS
Adjunctive treatment with dexamethasone improves survival in patients over 14 years of age with tuberculous meningitis but probably does not prevent severe disability.
Thwaites
Guy E
GE
Oxford University Clinical Research Unit at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. guy.thwaites@btinternet.com
Nguyen
Duc Bang
DB
Nguyen
Huy Dung
HD
Hoang
Thi Quy
TQ
Do
Thi Tuong Oanh
TT
Nguyen
Thi Cam Thoa
TC
Nguyen
Quang Hien
QH
Nguyen
Tri Thuc
TT
Nguyen
Ngoc Hai
NH
Nguyen
Thi Ngoc Lan
TN
Nguyen
Ngoc Lan
NL
Nguyen
Hong Duc
HD
Vu
Ngoc Tuan
NT
Cao
Huu Hiep
HH
Tran
Thi Hong Chau
TH
Pham
Phuong Mai
PM
Nguyen
Thi Dung
TD
Stepniewska
Kasia
K
White
Nicholas J
NJ
Tran
Tinh Hien
TH
Farrar
Jeremy J
JJ
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016019:Survival Analysis; D014390:Tuberculosis, Meningeal / Q000150:complications / Q000188:drug therapy* / Q000401:mortality
D000276:Adjuvants, Immunologic; D005938:Glucocorticoids; D003907:Dexamethasone