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Previous Volume 351:1741-1751 October 21, 2004 Number 17 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Perspective by Donald, P. R. Editorial by Quagliarello, V. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

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.

Source Information

From the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, and the Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom (G.E.T., K.S., N.J.W., J.J.F.); Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease, Ho Chi Minh City, Vietnam (N.D.B., Nguyen H. Dung, H.T.Q., D.T.T.O., N.T.C.T., N.Q.H., N.T.T., N.N.H., N.T.N.L., N.N.L., Nguyen H. Duc, V.N.T., C.H.H.); and Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam (T.T.H.C., P.P.M., N.T.D., T.T.H.).

Address reprint requests to Dr. Thwaites at the Oxford University Clinical Research Unit, the Hospital for Tropical Diseases, 190 Ben Ham Tu, Quan 5, Ho Chi Minh City, Vietnam, or at guy.thwaites{at}btinternet.com.

Full Text of this Article

Related Letters:

Dexamethasone for Tuberculous Meningitis
Seligman S. J., Vagenakis A. G., Kyriazopoulou V., Marras T. K., Thwaites G. E., Quy H. T., Farrar J. J., Quagliarello V.
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N Engl J Med 2005; 352:628-630, Feb 10, 2005. Correspondence

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