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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003EPooled data from the SECURE and VITAL global phase 3 multicenter trials have demonstrated the effectiveness of isavuconazole in the treatment of invasive aspergillosis in patients with renal insufficiency. Other intravenous triazole antifungals are contraindicated in these patients. Dose adjustment of isavuconazole is not needed.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Einvasive aspergillosis\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eisavuconazole\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Etriazole antifungals\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Erenal dysfunction\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Einfectious diseases clinical trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Efungal infections\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003ETwo analyses of the pooled data from the global phase 3 multicenter VITAL [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00412893\u0026amp;atom=%2Fspmdc%2F15%2F48%2F9.atom\u0022\u003ENCT00412893\u003C\/a\u003E] and SECURE [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00634049\u0026amp;atom=%2Fspmdc%2F15%2F48%2F9.atom\u0022\u003ENCT00634049\u003C\/a\u003E] trials have demonstrated the safety and effectiveness of the broad-spectrum triazole antifungal drug isavuconazole (ISA) in the treatment of invasive aspergillosis (IA) in patients with renal impairment. Renal dysfunction can occur in up to 40% of those with IA. ISA, which is available orally as water-soluble isavuconazonium sulfate, overcomes the limitations of other intravenous drugs available to treat IA that are associated with increased risk of renal toxicity in patients with preexisting renal dysfunction [Baddley J et al. \u003Cem\u003EClin Infect Dis\u003C\/em\u003E. 2010; Vandewoude K et al. \u003Cem\u003EJ Hosp Infect\u003C\/em\u003E. 2004].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ESECURE was a double-blind, parallel-group noninferiority trial that compared ISA and voriconazole in the treatment of IA and, more broadly, invasive fungal disease in 527 patients. Some of these patients had renal impairment. VITAL was an open-label trial involving 149 patients, and it examined the use of ISA in both fungal diseases. Both trials used a loading dose of ISA (200 mg TID intravenously on days 1 and 2), followed by ISA 200 mg QD intravenously or orally from day 3 to the end of treatment (days 84 and 180 in SECURE and VITAL, respectively). Patients were aged \u2265\u200518 years with proven\/probable IA, with or without renal impairment at baseline. The key end point was all-cause mortality through day 42. Secondary end points included all-cause mortality and probability of survival through day 84. Treatment success was the partial or complete resolution of clinical symptoms, physical findings, and radiological abnormalities. The type, frequency, and severity of treatment-emergent adverse effects (TEAEs) were recorded.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EOne of the pooled analyses was presented by Johan Maertens, MD, PhD, UZ Leuven, Leuven, Belgium. This analysis focused on 143 patients of the 676 in the pooled population who had proven\/probable IA treated with ISA. Thirty-one patients had renal impairment, and the remaining 112 did not. Patient characteristics at baseline are summarized in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16636\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16636\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16636\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003EPatient Characteristics at Baseline\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-13\u0022\u003EAll-cause mortality was similar in patients with (n\u2005=\u200531) or without (n\u2005=\u2005112) renal impairment at baseline through day 42 (4 [13%] vs 21 [19%]) and day 84 (8 [26%] vs 32 [29%], respectively). Overall successful response to treatment was similar in patients with (10 [32%]) and without (40 [36%]) renal impairment. The probability of survival determined by the Kaplan-Meier method was also similar in those with or without baseline renal impairment.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003ETEAEs occurred in all renal-impaired patients and 96% of patients without renal impairment (\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E). The most common TEAE was infections\/infestations, which occurred in 10 of 31 (32%) of those with renal impairment and 25 of 112 (22%) of those without renal impairment, followed by respiratory\/thoracic\/mediastinal disorders (5 [16%] vs 21 [19%]). Doubling of serum creatinine was noted in 1 of 30 patients (3%) with renal impairment and 14 of 109 patients (13%) without renal impairment.\u003C\/p\u003E\u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16637\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16637\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16637\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \u003Cp id=\u0022p-15\u0022 class=\u0022first-child\u0022\u003ETreatment-Emergent Adverse Outcomes\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-20\u0022\u003EAs discussed by William Hope, PhD, University of Liverpool, Liverpool, United Kingdom, the second analysis of the pooled SECURE and VITAL data focused on the minimum inhibitory concentration (MIC) of ISA on the various fungal pathogens.\u003C\/p\u003E\u003Cp id=\u0022p-21\u0022\u003EBaseline susceptibility of \u003Cem\u003EAspergillus\u003C\/em\u003E isolates to ISA was assessed using criteria of the European Committee on Antimicrobial Susceptibility Testing\u2019s definitive document E.DEF 9.1 [Rodriguez-Tudela JL et al. 2008]. Treatment success was the expert-assessed absence of clinical signs and symptoms at the end of treatment.\u003C\/p\u003E\u003Cp id=\u0022p-22\u0022\u003E\n            \u003Cem\u003EAspergillus\u003C\/em\u003E infection was confirmed microbiologically at baseline in 61 patients, comprising \u003Cem\u003EA fumigatus\u003C\/em\u003E (n\u2005=\u200531), \u003Cem\u003EA flavus\u003C\/em\u003E (n\u2005=\u200515), \u003Cem\u003EA niger\u003C\/em\u003E (n\u2005=\u20059), \u003Cem\u003EA terreus\u003C\/em\u003E (n\u2005=\u20055), and \u003Cem\u003EA westerdijkiae\u003C\/em\u003E (n\u2005=\u20051). The MIC of ISA in these species ranged from 0.12 to \u0026gt;\u003Cstrong\u003E\u2005\u003C\/strong\u003E16 mg\/L. The assessed clinical success of treatment was 50% to 100% for species with MIC \u0026lt;\u003Cstrong\u003E\u2005\u003C\/strong\u003E16 mg\/L and was similar for \u003Cem\u003EA fumigatus\u003C\/em\u003E (71.0%), \u003Cem\u003EA flavus\u003C\/em\u003E (73.3%), \u003Cem\u003EA niger\u003C\/em\u003E (66.7%), and \u003Cem\u003EA terreus\u003C\/em\u003E (60.0%). The overall clinical success for all cases with microbiologic confirmation was 69% (42 of 61), indicating that the effectiveness of treatment may be unrelated to the MIC.\u003C\/p\u003E\u003Cp id=\u0022p-23\u0022\u003EThe analyses of the pooled SECURE and VITAL data substantiate the view that ISA is effective in the treatment of IA in patients with renal insufficiency, for whom other triazole antifungals may be restricted in use; they also indicate that dose adjustment for this patient population is not needed.\u003C\/p\u003E\u003Cp id=\u0022p-24\u0022\u003EISA has been approved for use in the United States for treatment of IA and mucormycosis in patients aged 18 years and older. Regulatory review in Europe is ongoing.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/48\/9.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzllu1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzllu1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}