title: 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.
abstract: 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.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: R
authors.initials: R
authors.lastname: Lin
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: Z
authors.initials: Z
authors.lastname: Fan
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
authors.forename: F
authors.initials: F
authors.lastname: Huang
authors.forename: H
authors.initials: H
authors.lastname: Zhou
authors.forename: D
authors.initials: D
authors.lastname: Nie
authors.forename: Z
authors.initials: Z
authors.lastname: Guo
authors.forename: Y
authors.initials: Y
authors.lastname: Mao
authors.forename: Y
authors.initials: Y
authors.lastname: Xiao
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019072:Antibiotic Prophylaxis / Q000379:methods*; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D002648:Child; D002681:China; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000209:etiology / Q000517:prevention & control*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole
keywords: allogeneic hematopoietic stem cell transplantation; antifungal prophylaxis; itraconazole