A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. U.K. Multicentre Antifungal Prophylaxis Study Group.
AuthorsMorgenstern, Godfrey R
Prentice, Archibald G
Prentice, H Grant
Ropner, Janet E
Warnock, David W
AffiliationChristie Hospital, Manchester.
MetadataShow full item record
AbstractFluconazole is widely used as antifungal prophylaxis but it is ineffective against Aspergillus. Itraconazole has a broader spectrum of activity but the capsules give erratic bioavailability in neutropenic patients. We compared itraconazole oral solution (which has an improved pharmacokinetic profile) with fluconazole for antifungal prophylaxis. Adults with haematological malignancies receiving chemotherapy or bone marrow transplants were randomly allocated 5 mg/kg/d itraconazole (itra) solution (288 episodes) or 100 mg fluconazole suspension (flu) (293 episodes) from before the onset of neutropenia until neutrophil recovery or suspected fungal infection. Outcomes were assessed by independent reviewers unaware of the prophylaxis allocation. More proven systemic fungal infections occurred in flu (Aspergillus four, Candida tropicalis one, C. krusei one) than itra (C. albicans one) and more of these were fatal (four versus nil). This difference reached statistical significance when first study episodes were considered separately (six flu versus nil itra, P = 0.03). Significantly more deaths of presumed fungal origin occurred in flu than itra (seven versus nil, P = 0.024). There were significantly more cases of proven aspergillosis in flu than itra (six versus nil, P = 0.038, 5/6 cases were fatal) if those occurring outside the study period are included. Significantly more patients receiving flu required amphotericin B (58 v 39, P = 0.043) but this may have been affected by the fact that the study was not blinded. There were 11 proven mucosal candidal infections in flu and four in itra. Itraconazole solution and fluconazole provide effective prophylaxis against Candida but itraconazole affords greater protection against fatal aspergillosis.
CitationA randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. U.K. Multicentre Antifungal Prophylaxis Study Group. 1999, 105 (4):901-11 Br. J. Haematol.
JournalBritish Journal of Haematology
- An open-label randomized trial comparing itraconazole oral solution with fluconazole oral solution for primary prophylaxis of fungal infections in patients with haematological malignancy and profound neutropenia.
- Authors: Glasmacher A, Cornely O, Ullmann AJ, Wedding U, Bodenstein H, Wandt H, Boewer C, Pasold R, Wolf HH, Hänel M, Dölken G, Junghanss C, Andreesen R, Bertz H, Itraconazole Research Group of Germany.
- Issue date: 2006 Feb
- Fluconazole versus itraconazole for the prevention of fungal infections in haemato-oncology.
- Authors: Huijgens PC, Simoons-Smit AM, van Loenen AC, Prooy E, van Tinteren H, Ossenkoppele GJ, Jonkhoff AR
- Issue date: 1999 May
- Antifungal prophylaxis with itraconazole oral solution in neutropenic patients.
- Authors: Kibbler CC
- Issue date: 1999
- Randomized controlled trial of oral itraconazole solution versus intravenous/oral fluconazole for prevention of fungal infections in liver transplant recipients.
- Authors: Winston DJ, Busuttil RW
- Issue date: 2002 Sep 15
- Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: a meta-analysis of randomised-controlled trials.
- Authors: Vardakas KZ, Michalopoulos A, Falagas ME
- Issue date: 2005 Oct