title: Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults.
abstract: 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.
authors.affiliation: Oxford University Clinical Research Unit at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. guy.thwaites@btinternet.com
authors.forename: Guy E
authors.initials: GE
authors.lastname: Thwaites
authors.forename: Duc Bang
authors.initials: DB
authors.lastname: Nguyen
authors.forename: Huy Dung
authors.initials: HD
authors.lastname: Nguyen
authors.forename: Thi Quy
authors.initials: TQ
authors.lastname: Hoang
authors.forename: Thi Tuong Oanh
authors.initials: TT
authors.lastname: Do
authors.forename: Thi Cam Thoa
authors.initials: TC
authors.lastname: Nguyen
authors.forename: Quang Hien
authors.initials: QH
authors.lastname: Nguyen
authors.forename: Tri Thuc
authors.initials: TT
authors.lastname: Nguyen
authors.forename: Ngoc Hai
authors.initials: NH
authors.lastname: Nguyen
authors.forename: Thi Ngoc Lan
authors.initials: TN
authors.lastname: Nguyen
authors.forename: Ngoc Lan
authors.initials: NL
authors.lastname: Nguyen
authors.forename: Hong Duc
authors.initials: HD
authors.lastname: Nguyen
authors.forename: Ngoc Tuan
authors.initials: NT
authors.lastname: Vu
authors.forename: Huu Hiep
authors.initials: HH
authors.lastname: Cao
authors.forename: Thi Hong Chau
authors.initials: TH
authors.lastname: Tran
authors.forename: Phuong Mai
authors.initials: PM
authors.lastname: Pham
authors.forename: Thi Dung
authors.initials: TD
authors.lastname: Nguyen
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Tinh Hien
authors.initials: TH
authors.lastname: Tran
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Farrar
mesh_terms: 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
chemical_list: D000276:Adjuvants, Immunologic; D005938:Glucocorticoids; D003907:Dexamethasone