Itraconazole IV solution in the treatment of candidemia in non-neutropenic patients
© BioMed Central Ltd 2003
Published: 3 March 2003
To investigate the efficacy and safety of the itraconazole intravenous (IV) formulation followed by oral solution in the treatment of candidemia in non-neutropenics versus fluconazole.
This was an international multicenter, randomized, open-label study, sponsored by Johnson & Johnson Pharmaceutical Research and Development (Beerse, Belgium). The study involved patients with candidemia documented by at least one positive blood culture with isolation of yeast (presumed Candida spp.) within 4 days of study entry, and clinical evidence of infection. Patients were randomized to receive either itraconazole or fluconazole. Intravenous itraconazole 200 mg was given twice daily on days 1 and 2, and then once daily for 5 days (and for a further 7 days if the patient could not take or tolerate oral medication); subsequently, itracona-zole oral solution 200 mg twice daily was given until 14 days after resolution of symptoms and signs of fungal infection and cultures. Intravenous fluconazole 400 mg was given once daily for 7 days (extended for a further 7 days if required); then oral fluconazole 400 mg once daily was given until 14 days after resolution of infection and cultures. The intention-to-treat (ITT) population included all randomized patients who had candidemia documented by at least one positive blood culture of Candida spp. The primary efficacy measure was the investigators' global assessment of successful response to treatment at followup week 12.
The study was terminated early because of the very slow enrollment rate after 197 patients had been randomized (n = 99 itraconazole and n = 98 fluconazole). The ITT population consisted of 193 patients (n = 96 itraconazole and n = 97 fluconazole); however, only 37 patients receiving itraconazole and 44 patients receiving fluconazole could be evaluated for the primary efficacy measure. At week 12 of followup, itraconazole had a success rate of 92% (34 of 37 patients) compared with a 91% success rate for fluconazole (40 of 44 patients). The overall safety profiles of the itraconazole and fluconazole groups were similar.
Results from this study do not indicate any clinically meaningful differences in efficacy or safety outcomes in patients with candidemia treated with itraconazole compared with those treated with fluconazole.