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Beardsley, J, Wolbers, M, Kibengo, F M, Ggayi, A-B M, Kamali, A, Cuc, 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, Heyderman, R, Mwinjiwa, E, van Oosterhout, J J, Imran, D, Basri, H, Mayxay, M, Dance, D, Phimmasone, P, Rattanavong, S, Lalloo, David 
ORCID: https://orcid.org/0000-0001-7680-2200 and Day, J N
(2016)
'Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis'. New England Journal of Medicine, Vol 374, pp. 542-554.
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Abstract
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.)
| Item Type: | Article |
|---|---|
| Corporate Authors: | CryptoDex Investigators |
| Subjects: | WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 245 Meningococcal infections WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.5 Complications |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > International Public Health Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1056/NEJMoa1509024 |
| Depositing User: | Annmarie Hand |
| Date Deposited: | 11 Feb 2016 16:01 |
| Last Modified: | 06 Dec 2018 11:20 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/5639 |
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