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Comparison of long‐term and short‐term administration of itraconazole for primary antifungal prophylaxis in recipients of allogeneic hematopoietic stem cell transplantation: a multicenter, randomized, open‐label trial
Author(s) -
Lin R.,
Xu X.,
Li Y.,
Sun J.,
Fan Z.,
Jiang Q.,
Huang F.,
Zhou H.,
Nie D.,
Guo Z.,
Mao Y.,
Xiao Y.,
Liu Q.
Publication year - 2014
Publication title -
transplant infectious disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.69
H-Index - 67
eISSN - 1399-3062
pISSN - 1398-2273
DOI - 10.1111/tid.12192
Subject(s) - medicine , clinical endpoint , transplantation , randomization , itraconazole , randomized controlled trial , hematopoietic stem cell transplantation , multicenter trial , incidence (geometry) , surgery , cumulative incidence , antifungal , multicenter study , physics , dermatology , optics
Background The optimal agents and duration of primary antifungal prophylaxis in recipients of allogeneic hematopoietic stem cell transplantation (allo‐ HSCT ) remain a matter of discussion. Objective Our objective was to compare the efficacy and safety of long‐term and short‐term administration of itraconazole ( ITCZ ) for primary antifungal prophylaxis in allo‐ HSCT recipients. Methods This multicenter, randomized, open‐label pilot study was performed in 4 transplant centers in China. Recipients of allo‐ HSCT without a history of invasive fungal disease ( IFD ) were randomly assigned to the long‐term or the short‐term arm. Randomization was carried out by a center computer system. Intravenous ITCZ was given to the patients in both study arms with a loading dose of 400 mg/day for 2 days followed by 200 mg/day until day +14 or when the white blood cell count was >1.0 × 10 9 /L, and then switched to oral ITCZ solution; prophylaxis was continued until day +30 post transplantation in the short‐term arm or until day +90 in the long‐term arm. The trough serum concentrations of ITCZ also were measured. The primary study endpoint was the incidence of IFD (proven, probable, and possible) within day +90 post transplantation. Results A total of 128 recipients were enrolled in this study; 59 of them were randomized to the long‐term arm and 62 were randomized to the short‐term arm, forming the modified intent‐to‐treat ( mITT ) set. The incidence of IFD within day +90, the primary endpoint, was not significantly different between the 2 arms for the mITT set (6.78% in the long‐term arm vs. 6.45% in the short‐term arm, P = 0.94), or for the per‐protocol set (6.90% in the long‐term arm vs. 6.67% in the short‐term arm, P = 0.96). From day +30 to day +90, the incidence of IFD was 0% and 6.45%, respectively, in the patients with long‐term and short‐term prophylaxis for the mITT set ( P = 0.11). The mean trough serum concentrations of ITCZ was maintained at >500 ng/mL throughout administration. The incidences of withdrawal because of drug‐related adverse events in patients with long‐term and short‐term prophylaxis were 6.78% and 0%, respectively ( P = 0.05). Conclusions Long‐term and short‐term administration of ITCZ both seemed effective in preventing IFD in recipients of allo‐ HSCT . Further study with large sample size should be performed to evaluate this result. ITCZ shows the same pharmacokinetics in recipients of allo‐ HSCT as in non‐recipients.