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

A randomised non-inferiority trial

B. J. Kullberg, J. D. Sobel, M. Ruhnke, P. G. Pappas, C. Viscoli, J. H. Rex, J. D. Cleary, E. Rubinstein, L. W P Church, J. M. Brown, H. T. Schlamm, I. T. Oborska, F. Hilton, M. R. Hodges

Research output: Contribution to journalArticle

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Abstract

Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Relevance to practice: 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.

Original languageEnglish
Pages (from-to)1435-1442
Number of pages8
JournalLancet
Volume366
Issue number9495
DOIs
Publication statusPublished - Oct 22 2005

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Candidemia
Fluconazole
Amphotericin B
Therapeutics
Regimen B
Voriconazole
Echinocandins
Aspergillosis
Candidiasis
Poisons
Advisory Committees
Candida
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients : A randomised non-inferiority trial. / Kullberg, B. J.; Sobel, J. D.; Ruhnke, M.; Pappas, P. G.; Viscoli, C.; Rex, J. H.; Cleary, J. D.; Rubinstein, E.; Church, L. W P; Brown, J. M.; Schlamm, H. T.; Oborska, I. T.; Hilton, F.; Hodges, M. R.

In: Lancet, Vol. 366, No. 9495, 22.10.2005, p. 1435-1442.

Research output: Contribution to journalArticle

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 2005, 'Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: A randomised non-inferiority trial', Lancet, vol. 366, no. 9495, pp. 1435-1442. https://doi.org/10.1016/S0140-6736(05)67490-9
Kullberg, B. J. ; Sobel, J. D. ; Ruhnke, M. ; Pappas, P. G. ; Viscoli, C. ; Rex, J. H. ; Cleary, J. D. ; Rubinstein, E. ; Church, L. W P ; Brown, J. M. ; Schlamm, H. T. ; Oborska, I. T. ; Hilton, F. ; Hodges, M. R. / Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients : A randomised non-inferiority trial. In: Lancet. 2005 ; Vol. 366, No. 9495. pp. 1435-1442.
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abstract = "Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Relevance to practice: 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.",
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T1 - Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients

T2 - A randomised non-inferiority trial

AU - Kullberg, B. J.

AU - Sobel, J. D.

AU - Ruhnke, M.

AU - Pappas, P. G.

AU - Viscoli, C.

AU - Rex, J. H.

AU - Cleary, J. D.

AU - Rubinstein, E.

AU - Church, L. W P

AU - Brown, J. M.

AU - Schlamm, H. T.

AU - Oborska, I. T.

AU - Hilton, F.

AU - Hodges, M. R.

PY - 2005/10/22

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N2 - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Relevance to practice: 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.

AB - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Relevance to practice: 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.

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