Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis.
Background: Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600,000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality...
| Published in: | New England Journal of Medicine Vol. 374; no. 6; pp. 542 - 555 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
| Format: | research randomized controlled trial Journal Article |
| Published: |
New England Journal of Medicine
2/11/2016
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=113172040&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 113172040 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00284793 NEJ jtl: New England Journal of Medicine issn: 00284793 maglogo: N pubinfo: dt: 2/11/2016 vid: 374 iid: 6 pid: 388 pub: New England Journal of Medicine place: Waltham, Massachusetts artinfo: ui: 113172040 113172040 NLM26863355 113172040 10.1056/NEJMoa1509024 NLM26863355 PMC4778268 113172040 ppf: 542 ppct: 13 formats: tig: atl: Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis. aug: au: Beardsley, J. Wolbers, M. Kibengo, F. M. Ggayi, A.-B.M. Kamali, A. Cue, N. T. K. Binh, T. Q. Chau, N. V. V. Farrar, J. Merson, L. Phuong, L. Thwaites, G. Van Kinh, N. Thuy, P. T. Chierakul, W. Siriboon, S. Thiansukhon, E. Onsanit, S. Supphamongkholchaikul, W. Chan, A. K. affil: The Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam sug: subj: Meningitis, Cryptococcal Drug Therapy Cryptococcus Glucocorticoids Therapeutic Use AIDS-Related Opportunistic Infections Drug Therapy Dexamethasone Therapeutic Use Intracranial Pressure Dexamethasone Adverse Effects Male Adult Glucocorticoids Adverse Effects Human Kaplan-Meier Estimator AIDS-Related Opportunistic Infections Mortality Double-Blind Studies Female Colony Count, Microbial Meningitis, Cryptococcal Mortality Cerebrospinal Fluid Microbiology Treatment Failure Validation Studies Comparative Studies Evaluation Research Multicenter Studies Randomized Controlled Trials Funding Source Adult: 19-44 years Male Female ab: Background: Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600,000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality among patients with other forms of meningitis in some populations, but their use is untested in patients with cryptococcal meningitis.Methods: In this double-blind, randomized, placebo-controlled trial, we recruited adult patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand, Indonesia, Laos, Uganda, and Malawi. All the patients received either dexamethasone or placebo for 6 weeks, along with combination antifungal therapy with amphotericin B and fluconazole.Results: The trial was stopped for safety reasons after the enrollment of 451 patients. Mortality was 47% in the dexamethasone group and 41% in the placebo group by 10 weeks (hazard ratio in the dexamethasone group, 1.11; 95% confidence interval [CI], 0.84 to 1.47; P=0.45) and 57% and 49%, respectively, by 6 months (hazard ratio, 1.18; 95% CI, 0.91 to 1.53; P=0.20). The percentage of patients with disability at 10 weeks was higher in the dexamethasone group than in the placebo group, with 13% versus 25% having a prespecified good outcome (odds ratio, 0.42; 95% CI, 0.25 to 0.69; P<0.001). Clinical adverse events were more common in the dexamethasone group than in the placebo group (667 vs. 494 events, P=0.01), with more patients in the dexamethasone group having grade 3 or 4 infection (48 vs. 25 patients, P=0.003), renal events (22 vs. 7, P=0.004), and cardiac events (8 vs. 0, P=0.004). Fungal clearance in cerebrospinal fluid was slower in the dexamethasone group. Results were consistent across Asian and African sites.Conclusions: Dexamethasone did not reduce mortality among patients with HIV-associated cryptococcal meningitis and was associated with more adverse events and disability than was placebo. (Funded by the United Kingdom Department for International Development and others through the Joint Global Health Trials program; Current Controlled Trials number, ISRCTN59144167.). pubtype: Academic Journal doctype: research randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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