Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial

• Published in: The Lancet (British edition) 2005-10, Vol.366 (9495), p.1435-1442
• Main Authors: Kullberg, BJ, Sobel, JD, Ruhnke, M, Pappas, PG, Viscoli, C, Rex, JH, Cleary, JD, Rubinstein, E, Church, LWP, Brown, JM, Schlamm, HT, Oborska, IT, Hilton, F, Hodges, MR
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B - adverse effects; Amphotericin B - therapeutic use; Antifungal Agents - adverse effects; Antifungal Agents - therapeutic use; APACHE; Blood; Candidiasis - classification; Candidiasis - drug therapy; Candidiasis - mortality; Drug Therapy, Combination; Female; Fluconazole - adverse effects; Fluconazole - therapeutic use; Fungi; Humans; Infections; Male; Medical treatment; Middle Aged; Pharmaceuticals; Prescription drugs; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Treatment Outcome; Triazoles - adverse effects; Triazoles - therapeutic use; Voriconazole
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(05)67490-9

Voriconazole has proven efficacy against invasive aspergillosis and oesophageal candidiasis. This multicentre, randomised, non-inferiority study compared voriconazole with a regimen of amphotericin B followed by fluconazole for the treatment of candidaemia in non-neutropenic patients. Non-neutropenic patients with a positive blood culture for a species of candida and clinical evidence of infection were enrolled. Patients were randomly assigned, in a 2:1 ratio, either voriconazole (n=283) or amphotericin B followed by fluconazole (n=139). The primary efficacy analysis was based on clinical and mycological response 12 weeks after the end of treatment, assessed by an independent data-review committee unaware of treatment assignment. Of 422 patients randomised, 370 were included in the modified intention-to-treat population. Voriconazole was non-inferior to amphotericin B/fluconazole in the primary efficacy analysis, with successful outcomes in 41% of patients in both treatment groups (95% CI for difference −10·6% to 10·6%). At the last evaluable assessment, outcome was successful in 162 (65%) patients assigned voriconazole and 87 (71%) assigned amphotericin B/fluconazole (p=0·25). Voriconazole cleared blood cultures as quickly as amphotericin B/fluconazole (median time to negative blood culture, 2·0 days). Treatment discontinuations due to all-cause adverse events were more frequent in the voriconazole group, although most discontinuations were due to non-drug-related events and there were significantly fewer serious adverse events and cases of renal toxicity than in the amphotericin B/fluconazole group. Voriconazole was as effective as the regimen of amphotericin B followed by fluconazole in the treatment of candidaemia in non-neutropenic patients, and with fewer toxic effects. There are several options for treatment of candidaemia in non-neutropenic patients, including amphotericin B, fluconazole, voriconazole, and echinocandins. Voriconazole can be given both as initial intravenous treatment and as an oral stepdown agent.