{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:14:48Z","timestamp":1768871688457,"version":"3.49.0"},"reference-count":19,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T00:00:00Z","timestamp":1590624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Fungal infections are a major complication of neutropaenia following chemotherapy. Their early diagnosis is difficult, and empirical antifungal treatment is widely used, and uses of less toxic drugs that reduce breakthrough infection are required.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We conducted a multicentre, open\u2010label, randomised, non\u2010inferiority trial to compare the safety and efficacy of intravenous itraconazole (ivITCZ) and liposomal amphotericin B (LAmB) as empirical antifungal therapy in patients with haematological malignancies with neutropaenia and persistent fever.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with haematological malignancies who developed fever refractory to broad\u2010spectrum antibacterial agents under neutropaenia conditions were enrolled. Patients were randomised for treatment with LAmB (3.0\u00a0mg\/kg\/d) or ivITCZ (induction: 400\u00a0mg\/d, maintenance: 200\u00a0mg\/d).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Observed overall favourable response rates of 17\/52 (32.7%) and 18\/50 (36.0%) in the LAmB and ivITCZ groups, with a model\u2010based estimate of a 4% difference (90% CI, \u221212% to 20%), did not fulfil the statistical non\u2010inferiority criterion. In the LAmB group, there were two cases of breakthrough infection and five cases of probable invasive fungal disease, whereas in the itraconazole group, neither breakthrough infection nor probable invasive fungal disease occurred. Patients in the ivITCZ group had significantly fewer grade 3\u20104 hypokalaemia\u2010related events than LAmB group patients (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.01). The overall incidence of adverse events tended to be lower in the ivITCZ group (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.07).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ivITCZ showed similar efficacy and safety as LAmB as empirical antifungal therapy in haematological malignancy patients with febrile neutropaenia, although the small sample size and various limitations prevented demonstration of its non\u2010inferiority.<\/jats:p><\/jats:sec>","DOI":"10.1111\/myc.13100","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T16:41:36Z","timestamp":1589215296000},"page":"794-801","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Intravenous itraconazole compared with liposomal amphotericin B as empirical antifungal therapy in patients with neutropaenia and persistent fever"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5234-0507","authenticated-orcid":false,"given":"Isao","family":"Yoshida","sequence":"first","affiliation":[{"name":"Department of Hematologic Oncology National Hospital Organization Shikoku Cancer Center Matsuyama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko M.","family":"Saito","sequence":"additional","affiliation":[{"name":"Clinical Research Center National Hospital Organization Nagoya Medical Center Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Clinical Biostatistics Graduate School of Medicine Kyoto University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilseung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Kyushu Cancer Center Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michihiro","family":"Hidaka","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Kumamoto Medical Center Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiko","family":"Miyata","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Nagoya Medical Center Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiko","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Kumamoto Medical Center Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Hematology and Clinical Research Institute National Hospital Organization Kyushu Medical Center Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiya","family":"Kagoo","sequence":"additional","affiliation":[{"name":"Department of Hematology and Internal Medicine National Hospital Organization Tokyo Medical Center Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroatsu","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Nagoya Medical Center Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromasa","family":"Niimi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Hospital Organization Hiroshima\u2010Nishi Medical Center Otake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Komeno","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Mito Medical Center Higashiibarakigun Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chikamasa","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Minami\u2010Okayama Medical Center Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumihito","family":"Tajima","sequence":"additional","affiliation":[{"name":"Stem Cell Transplantation Center National Hospital Organization Yonago Medical Center Yonago Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideyuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Nagoya Medical Center Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Takase","sequence":"additional","affiliation":[{"name":"Department of Hematology and Clinical Research Institute National Hospital Organization Kyushu Medical Center Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Ueno","sequence":"additional","affiliation":[{"name":"Department of Hematology and Internal Medicine National Hospital Organization Tokyo Medical Center Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Hospital Organization Hiroshima\u2010Nishi Medical Center Otake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsunori","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Kumamoto Medical Center Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Kyushu Cancer Center Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chikashi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Mito Medical Center Higashiibarakigun Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiro","family":"Kubonishi","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Okayama Medical Center Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazutaka","family":"Sunami","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Okayama Medical Center Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichiro","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Nagasaki Medical Center Omura Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aki","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Department of Hematologic Oncology National Hospital Organization Shikoku Cancer Center Matsuyama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihiro","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Bacteriology Osaka City University Graduate School of Medicine Osaka Japan"},{"name":"Department of Chemotherapy and Mycoses National Institute of Infectious Diseases Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitsugu","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy and Mycoses National Institute of Infectious Diseases Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Hematology National 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Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19920601)69:11<2653::AID-CNCR2820691106>3.0.CO;2-8"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/17.Supplement_2.S481"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/17.Supplement_2.S487"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/341305"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.27.12.1627"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/422723"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/427752"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/500323"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199903113401004"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200201243460403"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040446"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02183-17"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-135-6-200109180-00010"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.8.3807-3810.2005"},{"key":"e_1_2_8_16_1","unstructured":"YoshidaI.Multi\u2010centre prospective randomized trial intravenous itraconazole versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia (ILEAN study); university hospital medical information network clinical trial registry (UMIN000005529).2011.https:\/\/upload.umin.ac.jp\/cgi\u2010open\u2010bin\/ctr_e\/ctr_view.cgi?recptno=R000006558. 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