TY - JOUR
T1 - Adjunctive dexamethasone in HIV-associated cryptococcal meningitis
AU - Beardsley, J.
AU - Wolbers, M.
AU - Kibengo, F. M.
AU - Ggayi, A. B.M.
AU - Kamali, A.
AU - Cuc, N. T.K.
AU - Binh, T. Q.
AU - Chau, N. V.V.
AU - Farrar, J.
AU - Merson, L.
AU - Phuong, L.
AU - Thwaites, G.
AU - Van Kinh, N.
AU - Thuy, P. T.
AU - Chierakul, W.
AU - Siriboon, S.
AU - Thiansukhon, E.
AU - Onsanit, S.
AU - Supphamongkholchaikul, W.
AU - Chan, A. K.
AU - Heyderman, R.
AU - Mwinjiwa, E.
AU - Van Oosterhout, J. J.
AU - Imran, D.
AU - Basri, H.
AU - Mayxay, M.
AU - Dance, D.
AU - Phimmasone, P.
AU - Rattanavong, S.
AU - Lalloo, D. G.
AU - Day, J. N.
N1 - Publisher Copyright:
© Copyright 2016 Massachusetts Medical Society.
PY - 2016/2/11
Y1 - 2016/2/11
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84959300520&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1509024
DO - 10.1056/NEJMoa1509024
M3 - Article
C2 - 26863355
AN - SCOPUS:84959300520
SN - 0028-4793
VL - 374
SP - 543
EP - 554
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 6
ER -