The Comparison Between Long-Term and Short-Term Administration of Itraconazole for Primary Antifungal Prophylaxis in Recipients of Allogeneic Hematopoietic Stem Cell: A Multicenter, Randomized, Open-Label Trial (NCT01160952)

Invasive fungal infection (IFI) is a major cause of death in recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT). Although antifungal prophylaxis has been demonstrated effective for prevention of IFI after allo-HSCT, the optimal agents and the term of prophylaxis remain a matter of discussion. To investigate the effect of prophylaxis term for IFI after allo-HSCT, this multicenter, randomized, open-label study was conducted to compare the efficacy and safety between long-term and short-term administration of itraconazole for primary antifungal prophylaxis in recipients of allo-HSCT.

A total of 128 patients without a history of IFI were enrolled in this study. The primary antifungal prophylaxis was initiated when WBC count < 1.0*10^⋀9/L or on day 0. Itraconazole was administered intravenously with a loading dose of 400 mg·d⁻¹for 2 days followed by 200 mg·d⁻¹and switched to itraconazole orally on day +14 or when WBC count > 1.0*10^⋀9/L until 30 days post-HSCT in short-term arm or 90 days in long-term arm. The primary endpoint was the incidence of proven or probable IFI at 30 days and 90 days post-HSCT.

Of the 129 enrolled patients, date of 121 cases were used to determine the primary endpoint in the intent-to-treat population (59 for long-term and 62 for short-term) and 7 patients died of transplant complication or other causes before the use of itraconazole. The baseline demographic and transplant characteristic were similar in the two arms. The incidence of proven and probable IFI within 90 days post-transplants was 1.69%. Intent-to-treat analysis showed that there was not a significant difference in the rate of breakthrough IFI (proven or probable IFI) between he long-term and short-term arm (1.69% vs. 0%; P=0.311). The incidence of IFI (proven, probable, and possible) in long-term arm was higher than short-term arm within 90 days post-transplants (6.78% vs. 0%, P=0.03). Acute GVHD was the risk factor affected the occurrence of IFI after HSCT (OR= 2.750, 95%CI 1.939–3.901, P=0.023). Prophylaxis was interrupted in 11 patients due to event of intolerance, including 1 in the short-term arm and 10 in the long-term arm (P=0.004). The incidences of drug-related adverse events in the two arms were similar (6.78% vs. 3.23%, P=0.43). The incidence of overall survival at 6 months was 75.74% in long-term arm and 84.56% in short-term arm (P=0.459).

This study indicates that itraconazole was effective for prevention of IFI within 30 days post-HSCT. Whether the prolonged term administration of antifungal agent for prevention fungal infection is benefit to the recipients in allo-HSCT is worthy of further exploration.

This trial was registered at www.clinicaltrials.gov as NCT01160952.

No relevant conflicts of interest to declare.