An open-label trial of the prophylactic administration of voriconazole in patients who undergo allogeneic hematopoietic stem cell transplantation: study protocol

Invasive fungal infections, especially those caused by Aspergillus, can be fatal in patients who have undergone allogeneic hematopoietic stem cell transplantation. Fluconazole, itraconazole and micafungin can be used to prevent fungal infections in patients undergoing allogeneic hematopoietic stem cell transplantation, but fluconazole is not effective against Aspergillus, and itraconazole has less tolerability from gastrointestinal toxicity. Micafungin is approved for prophylaxis at a dose of 50 mg/day, less than a therapeutic dose. Voriconazole, the current preferred agent for invasive Aspergillus infection, is available in both oral and intravenous preparations, and has recently been approved for prophylaxis in Japan. Some US and European studies have reported on the prophylactic use of voriconazole, but the efficacy and safety of this has not been confirmed in Japan. Hence, this prospective study of voriconazole as prophylaxis against invasive fungal infections in patients who have received allogeneic hematopoietic stem cell transplantation is being performed to evaluate its efficacy and safety, including incidence rate of proven/probable invasive aspergillosis and other fungal infections, and adverse event(s) due to voriconazole administration. We are also investigating potential interactions between voriconazole and immunosuppressive drugs by monitoring the blood concentration of a calcineurin inhibitor in Japanese patients. Further, this study aims to improve the clinical outcomes of allogeneic hematopoietic stem cell transplantation recipients.