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Invasive aspergillosis (<jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content>) is the most common <jats:styled-content style=\"fixed-case\">IFD<\/jats:styled-content> caused by moulds but the prevalence of other rare mould diseases, such as mucormycosis, hyalohyphomycosis and phaeohyphomycosis, may be increasing. Treatments are available for <jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content>, but evidence to support efficacy and safety of antifungal agents for rare <jats:styled-content style=\"fixed-case\">IFD<\/jats:styled-content>s, or for <jats:styled-content style=\"fixed-case\">IFD<\/jats:styled-content>s in special patient populations, is limited or lacking. The <jats:styled-content style=\"fixed-case\">VITAL<\/jats:styled-content> trial was conducted to assess the efficacy and safety of isavuconazole for the treatment of patients with <jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content> and renal impairment, or with <jats:styled-content style=\"fixed-case\">IFD<\/jats:styled-content>s caused by rare moulds, yeasts or dimorphic fungi. These patients stand to benefit most from a new treatment option but are unlikely to be included in a randomised, controlled trial. In this article, we review the challenges faced in the design and conduct of the <jats:styled-content style=\"fixed-case\">VITAL<\/jats:styled-content> trial. We also review the findings of <jats:styled-content style=\"fixed-case\">VITAL<\/jats:styled-content>, which included evidence of the efficacy and safety of isavuconazole. Finally, we consider the importance of trials such as <jats:styled-content style=\"fixed-case\">VITAL<\/jats:styled-content> to inform therapeutic decision making for clinicians faced with the challenge of treating patients with rare <jats:styled-content style=\"fixed-case\">IFD<\/jats:styled-content>s and as one paradigm of how to determine efficacy and safety of new drugs for rare and resistant infections without a suitable comparator.<\/jats:p>","DOI":"10.1111\/myc.12769","type":"journal-article","created":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T19:15:23Z","timestamp":1521832523000},"page":"420-429","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Isavuconazole treatment for rare fungal diseases and for invasive aspergillosis in patients with renal impairment: Challenges and lessons of the <scp>VITAL<\/scp> trial"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8742-3676","authenticated-orcid":false,"given":"John R.","family":"Perfect","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine Duke University  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9599-3137","authenticated-orcid":false,"given":"Oliver A.","family":"Cornely","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine Clinical Trials Centre Cologne, ZKS K\u00f6ln  Cologne Germany"},{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging\u2010Associated Diseases (CECAD) University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Heep","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Ostrosky\u2010Zeichner","sequence":"additional","affiliation":[{"name":"University of Texas Medical School at Houston  Houston TX USA"},{"name":"Memorial Hermann Texas Medical Center University of Texas  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Mullane","sequence":"additional","affiliation":[{"name":"Department of Medicine Section of Infectious Diseases and Global Health University of Chicago  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rochelle","family":"Maher","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney","family":"Croos\u2010Dabrera","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Lademacher","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Chen","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3708-8734","authenticated-orcid":false,"given":"Francisco M.","family":"Marty","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/595846"},{"key":"e_1_2_6_3_1","first-page":"269","article-title":"Epidemiological features of invasive mold infections among solid organ transplant recipients: PATH Alliance\u00ae registry analysis","volume":"55","author":"Husain S","year":"2017","journal-title":"Med Mycol"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-015-2374-1"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/1469-0691.12569"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw326"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.152900"},{"key":"e_1_2_6_8_1","unstructured":"European Medicines Agency.Vfend (voriconazole) summary of product characteristics.2014;http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Product_Information\/human\/000387\/WC500049756.pdf. 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