TY - JOUR
T1 - MSG-01
T2 - A randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting
AU - Ostrosky-Zeichner, Luis
AU - Shoham, Shmuel
AU - Vazquez, Jose
AU - Reboli, Annette
AU - Betts, Robert
AU - Barron, Michelle A.
AU - Schuster, Mindy
AU - Judson, Marc A.
AU - Revankar, Sanjay G.
AU - Caeiro, Juan Pablo
AU - Mangino, Julie E.
AU - Mushatt, David
AU - Bedimo, Roger
AU - Freifeld, Alison
AU - Nguyen, Minh Hong
AU - Kauffman, Carol A.
AU - Dismukes, William E.
AU - Westfall, Andrew O.
AU - Deerman, Jeanna Beth
AU - Wood, Craig
AU - Sobel, Jack D.
AU - Pappas, Peter G.
N1 - Funding Information:
Potential conflicts of interest. L. O.-Z. has received research grants from Merck, Astellas, Pfizer, and Associates of Cape Cod, and is a consultant and speaker for and has received honoraria from Merck, Astellas, and Pfizer. S. S. receives research funding from Astellas, Merck, and Pfizer, and is a member of the Merck Scientific Advisory Board. J. V. has received honoraria from Astellas and Forest; has received grants from Merck, Astel-las, and Pfizer; and is a consultant for Astellas and Forest. R. Bed. has received research grants from Merck and Janssen Pharmaceuticals and has participated in ad hoc scientific advisory boards for Serono, ViiV, and Gilead Sciences. J. E. M. has received a research grant from Medline Industries and sits on an advisory board for Cepheid. S. G. R has received research funding from Merck, Astellas, and Pfizer. C. W. is a full-time employee of and own stocks in Merck. M. H. N. has received research support from Merck, Pfizer, and Astellas. C. A. K. has participated in other clinical trials from Merck. P. G. P has received grants and research support from Merck, Astellas, Gilead, and T2 Biosystems and is an ad hoc advisor for Merck, Astellas, Gilead, Scynexis, Viamet, and T2 Biosystems. All other authors report no potential conflicts.
PY - 2014/5/1
Y1 - 2014/5/1
N2 - Background. Invasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting.Methods. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects' (1,3)-β-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline.Results. The incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively, for prophylaxis (P =. 14), and 30.4% (31/102) and 18.8% (22/117), respectively, for the preemptive approach (P =. 04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences.Conclusions. Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study.Clinical Trials Registration. NCT00520234.
AB - Background. Invasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting.Methods. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects' (1,3)-β-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline.Results. The incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively, for prophylaxis (P =. 14), and 30.4% (31/102) and 18.8% (22/117), respectively, for the preemptive approach (P =. 04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences.Conclusions. Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study.Clinical Trials Registration. NCT00520234.
KW - ICU
KW - caspofungin
KW - invasive candidiasis
KW - preemptive therapy
KW - prophylaxis
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U2 - 10.1093/cid/ciu074
DO - 10.1093/cid/ciu074
M3 - Article
C2 - 24550378
AN - SCOPUS:84898922226
SN - 1058-4838
VL - 58
SP - 1219
EP - 1226
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 9
ER -